Neil Osterweil

SAN ANTONIO – When an earthquake or other natural disaster strikes, adult day health centers can play a critical role in feeding, housing, and relocating elderly members of the community with more serious health needs, reported administrators of a center who developed an impromptu disaster-management plan in the immediate aftermath of a 2010 earthquake.

After a 7.2 Richter magnitude quake in Baja California, Mexico, on Easter Sunday 2010, the staff of the Alegria Adult Day Healthcare Center (ADHC) in nearby Calexico, Calif., took on the task of helping displaced residents from an adjacent assisted living facility that had been irreparably damaged by the tremors, according to Dr. Bernardo Ng of the department of psychiatry at the University of California, San Diego, and medical director of the Alegria ADHC.

The staffers contacted primary care physicians to discuss medical needs, arranged access to clothing, meals, transportation, and nursing services for suddenly homeless seniors, and helped prevent exacerbations or new onset of mental illness, they reported in a poster presentation at the annual meeting of the American Association for Geriatric Psychiatry.

"An ADHC that has the expertise of dealing with older adults on a daily basis should play a principal role in this kind of disaster plan. A key factor to be successful in whatever you want to carry out is that you partner with agencies or entities involved with whatever resources are available in the community," Dr. Ng said in an interview.

He acknowledged that, as a day facility, his center did not have a specific plan in place to act as a surrogate for the assisted living facility. As a result, he and his colleagues had to make it up as they went along.

The condemned building, a former hotel that had served as an assisted living facility since 1999, housed 98 seniors who had to be evacuated overnight, when building inspectors condemned it as unsound after the quake. The residents were relocated to local hotels but had no access to their clothes, medications, or personal belongings.

On the 3rd through 5th days after the seismic rift, the day center staff provided the residents with meals and transportation, and contacted their primary care physicians to discuss immediate needs. Many of the primary care offices and local pharmacies were damaged in the quake and remained closed for several days after the event.

In addition to providing the seniors with their own clothing and helping them with hygiene such as showering and shaving, the staff performed blood pressure and glycemia checks, provided physical therapy and regular activities, conducted tuberculosis screening and cognitive screening, and contacted family members.

Thirty days after the event, patients were reported to be more anxious, but none required hospitalization. No changes were required in psychotherapy or in medications, and no new onset mental illnesses were reported. The percentage of assisted living residents who attended the day center rose from 15% before the quake to 25% afterward. Some of the other displaced seniors went to stay with families out of town or friends, and those who were able to live more independently relocated to senior apartments, primarily outside the city.

"Disaster management after an earthquake is especially challenging, since there is little warning, an inability to predict potential scale of impairment of mental health services, and a loss of broad infrastructure," the authors wrote.

They noted that their sample was relatively small, but with appropriate support and monitoring, such plans could help to minimize the negative mental health consequences of disasters in larger communities.

SAN ANTONIO – When an earthquake or other natural disaster strikes, adult day health centers can play a critical role in feeding, housing, and relocating elderly members of the community with more serious health needs, reported administrators of a center who developed an impromptu disaster-management plan in the immediate aftermath of a 2010 earthquake.

After a 7.2 Richter magnitude quake in Baja California, Mexico, on Easter Sunday 2010, the staff of the Alegria Adult Day Healthcare Center (ADHC) in nearby Calexico, Calif., took on the task of helping displaced residents from an adjacent assisted living facility that had been irreparably damaged by the tremors, according to Dr. Bernardo Ng of the department of psychiatry at the University of California, San Diego, and medical director of the Alegria ADHC.

The staffers contacted primary care physicians to discuss medical needs, arranged access to clothing, meals, transportation, and nursing services for suddenly homeless seniors, and helped prevent exacerbations or new onset of mental illness, they reported in a poster presentation at the annual meeting of the American Association for Geriatric Psychiatry.

"An ADHC that has the expertise of dealing with older adults on a daily basis should play a principal role in this kind of disaster plan. A key factor to be successful in whatever you want to carry out is that you partner with agencies or entities involved with whatever resources are available in the community," Dr. Ng said in an interview.

He acknowledged that, as a day facility, his center did not have a specific plan in place to act as a surrogate for the assisted living facility. As a result, he and his colleagues had to make it up as they went along.

The condemned building, a former hotel that had served as an assisted living facility since 1999, housed 98 seniors who had to be evacuated overnight, when building inspectors condemned it as unsound after the quake. The residents were relocated to local hotels but had no access to their clothes, medications, or personal belongings.

On the 3rd through 5th days after the seismic rift, the day center staff provided the residents with meals and transportation, and contacted their primary care physicians to discuss immediate needs. Many of the primary care offices and local pharmacies were damaged in the quake and remained closed for several days after the event.

In addition to providing the seniors with their own clothing and helping them with hygiene such as showering and shaving, the staff performed blood pressure and glycemia checks, provided physical therapy and regular activities, conducted tuberculosis screening and cognitive screening, and contacted family members.

Thirty days after the event, patients were reported to be more anxious, but none required hospitalization. No changes were required in psychotherapy or in medications, and no new onset mental illnesses were reported. The percentage of assisted living residents who attended the day center rose from 15% before the quake to 25% afterward. Some of the other displaced seniors went to stay with families out of town or friends, and those who were able to live more independently relocated to senior apartments, primarily outside the city.

"Disaster management after an earthquake is especially challenging, since there is little warning, an inability to predict potential scale of impairment of mental health services, and a loss of broad infrastructure," the authors wrote.

They noted that their sample was relatively small, but with appropriate support and monitoring, such plans could help to minimize the negative mental health consequences of disasters in larger communities.

SAN ANTONIO – When an earthquake or other natural disaster strikes, adult day health centers can play a critical role in feeding, housing, and relocating elderly members of the community with more serious health needs, reported administrators of a center who developed an impromptu disaster-management plan in the immediate aftermath of a 2010 earthquake.

After a 7.2 Richter magnitude quake in Baja California, Mexico, on Easter Sunday 2010, the staff of the Alegria Adult Day Healthcare Center (ADHC) in nearby Calexico, Calif., took on the task of helping displaced residents from an adjacent assisted living facility that had been irreparably damaged by the tremors, according to Dr. Bernardo Ng of the department of psychiatry at the University of California, San Diego, and medical director of the Alegria ADHC.

The staffers contacted primary care physicians to discuss medical needs, arranged access to clothing, meals, transportation, and nursing services for suddenly homeless seniors, and helped prevent exacerbations or new onset of mental illness, they reported in a poster presentation at the annual meeting of the American Association for Geriatric Psychiatry.

"An ADHC that has the expertise of dealing with older adults on a daily basis should play a principal role in this kind of disaster plan. A key factor to be successful in whatever you want to carry out is that you partner with agencies or entities involved with whatever resources are available in the community," Dr. Ng said in an interview.

He acknowledged that, as a day facility, his center did not have a specific plan in place to act as a surrogate for the assisted living facility. As a result, he and his colleagues had to make it up as they went along.

The condemned building, a former hotel that had served as an assisted living facility since 1999, housed 98 seniors who had to be evacuated overnight, when building inspectors condemned it as unsound after the quake. The residents were relocated to local hotels but had no access to their clothes, medications, or personal belongings.

On the 3rd through 5th days after the seismic rift, the day center staff provided the residents with meals and transportation, and contacted their primary care physicians to discuss immediate needs. Many of the primary care offices and local pharmacies were damaged in the quake and remained closed for several days after the event.

In addition to providing the seniors with their own clothing and helping them with hygiene such as showering and shaving, the staff performed blood pressure and glycemia checks, provided physical therapy and regular activities, conducted tuberculosis screening and cognitive screening, and contacted family members.

Thirty days after the event, patients were reported to be more anxious, but none required hospitalization. No changes were required in psychotherapy or in medications, and no new onset mental illnesses were reported. The percentage of assisted living residents who attended the day center rose from 15% before the quake to 25% afterward. Some of the other displaced seniors went to stay with families out of town or friends, and those who were able to live more independently relocated to senior apartments, primarily outside the city.

"Disaster management after an earthquake is especially challenging, since there is little warning, an inability to predict potential scale of impairment of mental health services, and a loss of broad infrastructure," the authors wrote.

They noted that their sample was relatively small, but with appropriate support and monitoring, such plans could help to minimize the negative mental health consequences of disasters in larger communities.

SAN ANTONIO – When an earthquake or other natural disaster strikes, adult day health centers can play a critical role in feeding, housing, and relocating elderly members of the community with more serious health needs, reported administrators of a center who developed an impromptu disaster-management plan in the immediate aftermath of a 2010 earthquake.

After a 7.2 Richter magnitude quake in Baja California, Mexico, on Easter Sunday 2010, the staff of the Alegria Adult Day Healthcare Center (ADHC) in nearby Calexico, Calif., took on the task of helping displaced residents from an adjacent assisted living facility that had been irreparably damaged by the tremors, according to Dr. Bernardo Ng of the department of psychiatry at the University of California, San Diego, and medical director of the Alegria ADHC.

The staffers contacted primary care physicians to discuss medical needs, arranged access to clothing, meals, transportation, and nursing services for suddenly homeless seniors, and helped prevent exacerbations or new onset of mental illness, they reported in a poster presentation at the annual meeting of the American Association for Geriatric Psychiatry.

"An ADHC that has the expertise of dealing with older adults on a daily basis should play a principal role in this kind of disaster plan. A key factor to be successful in whatever you want to carry out is that you partner with agencies or entities involved with whatever resources are available in the community," Dr. Ng said in an interview.

He acknowledged that, as a day facility, his center did not have a specific plan in place to act as a surrogate for the assisted living facility. As a result, he and his colleagues had to make it up as they went along.

The condemned building, a former hotel that had served as an assisted living facility since 1999, housed 98 seniors who had to be evacuated overnight, when building inspectors condemned it as unsound after the quake. The residents were relocated to local hotels but had no access to their clothes, medications, or personal belongings.

On the 3rd through 5th days after the seismic rift, the day center staff provided the residents with meals and transportation, and contacted their primary care physicians to discuss immediate needs. Many of the primary care offices and local pharmacies were damaged in the quake and remained closed for several days after the event.

In addition to providing the seniors with their own clothing and helping them with hygiene such as showering and shaving, the staff performed blood pressure and glycemia checks, provided physical therapy and regular activities, conducted tuberculosis screening and cognitive screening, and contacted family members.

Thirty days after the event, patients were reported to be more anxious, but none required hospitalization. No changes were required in psychotherapy or in medications, and no new-onset mental illnesses were reported. The percentage of assisted living residents who attended the day center rose from 15% before the quake to 25% afterward. Some of the other displaced seniors went to stay with families out of town or friends, and those who were able to live more independently relocated to senior apartments, primarily outside the city.

"Disaster management after an earthquake is especially challenging, since there is little warning, an inability to predict potential scale of impairment of mental health services, and a loss of broad infrastructure," the authors wrote.

They noted that their sample was relatively small, but with appropriate support and monitoring, such plans could help to minimize the negative mental health consequences of disasters in larger communities.

SAN ANTONIO – When an earthquake or other natural disaster strikes, adult day health centers can play a critical role in feeding, housing, and relocating elderly members of the community with more serious health needs, reported administrators of a center who developed an impromptu disaster-management plan in the immediate aftermath of a 2010 earthquake.

After a 7.2 Richter magnitude quake in Baja California, Mexico, on Easter Sunday 2010, the staff of the Alegria Adult Day Healthcare Center (ADHC) in nearby Calexico, Calif., took on the task of helping displaced residents from an adjacent assisted living facility that had been irreparably damaged by the tremors, according to Dr. Bernardo Ng of the department of psychiatry at the University of California, San Diego, and medical director of the Alegria ADHC.

The staffers contacted primary care physicians to discuss medical needs, arranged access to clothing, meals, transportation, and nursing services for suddenly homeless seniors, and helped prevent exacerbations or new onset of mental illness, they reported in a poster presentation at the annual meeting of the American Association for Geriatric Psychiatry.

"An ADHC that has the expertise of dealing with older adults on a daily basis should play a principal role in this kind of disaster plan. A key factor to be successful in whatever you want to carry out is that you partner with agencies or entities involved with whatever resources are available in the community," Dr. Ng said in an interview.

He acknowledged that, as a day facility, his center did not have a specific plan in place to act as a surrogate for the assisted living facility. As a result, he and his colleagues had to make it up as they went along.

The condemned building, a former hotel that had served as an assisted living facility since 1999, housed 98 seniors who had to be evacuated overnight, when building inspectors condemned it as unsound after the quake. The residents were relocated to local hotels but had no access to their clothes, medications, or personal belongings.

On the 3rd through 5th days after the seismic rift, the day center staff provided the residents with meals and transportation, and contacted their primary care physicians to discuss immediate needs. Many of the primary care offices and local pharmacies were damaged in the quake and remained closed for several days after the event.

In addition to providing the seniors with their own clothing and helping them with hygiene such as showering and shaving, the staff performed blood pressure and glycemia checks, provided physical therapy and regular activities, conducted tuberculosis screening and cognitive screening, and contacted family members.

Thirty days after the event, patients were reported to be more anxious, but none required hospitalization. No changes were required in psychotherapy or in medications, and no new-onset mental illnesses were reported. The percentage of assisted living residents who attended the day center rose from 15% before the quake to 25% afterward. Some of the other displaced seniors went to stay with families out of town or friends, and those who were able to live more independently relocated to senior apartments, primarily outside the city.

"Disaster management after an earthquake is especially challenging, since there is little warning, an inability to predict potential scale of impairment of mental health services, and a loss of broad infrastructure," the authors wrote.

They noted that their sample was relatively small, but with appropriate support and monitoring, such plans could help to minimize the negative mental health consequences of disasters in larger communities.

SAN ANTONIO – When an earthquake or other natural disaster strikes, adult day health centers can play a critical role in feeding, housing, and relocating elderly members of the community with more serious health needs, reported administrators of a center who developed an impromptu disaster-management plan in the immediate aftermath of a 2010 earthquake.

After a 7.2 Richter magnitude quake in Baja California, Mexico, on Easter Sunday 2010, the staff of the Alegria Adult Day Healthcare Center (ADHC) in nearby Calexico, Calif., took on the task of helping displaced residents from an adjacent assisted living facility that had been irreparably damaged by the tremors, according to Dr. Bernardo Ng of the department of psychiatry at the University of California, San Diego, and medical director of the Alegria ADHC.

The staffers contacted primary care physicians to discuss medical needs, arranged access to clothing, meals, transportation, and nursing services for suddenly homeless seniors, and helped prevent exacerbations or new onset of mental illness, they reported in a poster presentation at the annual meeting of the American Association for Geriatric Psychiatry.

"An ADHC that has the expertise of dealing with older adults on a daily basis should play a principal role in this kind of disaster plan. A key factor to be successful in whatever you want to carry out is that you partner with agencies or entities involved with whatever resources are available in the community," Dr. Ng said in an interview.

He acknowledged that, as a day facility, his center did not have a specific plan in place to act as a surrogate for the assisted living facility. As a result, he and his colleagues had to make it up as they went along.

The condemned building, a former hotel that had served as an assisted living facility since 1999, housed 98 seniors who had to be evacuated overnight, when building inspectors condemned it as unsound after the quake. The residents were relocated to local hotels but had no access to their clothes, medications, or personal belongings.

On the 3rd through 5th days after the seismic rift, the day center staff provided the residents with meals and transportation, and contacted their primary care physicians to discuss immediate needs. Many of the primary care offices and local pharmacies were damaged in the quake and remained closed for several days after the event.

In addition to providing the seniors with their own clothing and helping them with hygiene such as showering and shaving, the staff performed blood pressure and glycemia checks, provided physical therapy and regular activities, conducted tuberculosis screening and cognitive screening, and contacted family members.

Thirty days after the event, patients were reported to be more anxious, but none required hospitalization. No changes were required in psychotherapy or in medications, and no new-onset mental illnesses were reported. The percentage of assisted living residents who attended the day center rose from 15% before the quake to 25% afterward. Some of the other displaced seniors went to stay with families out of town or friends, and those who were able to live more independently relocated to senior apartments, primarily outside the city.

"Disaster management after an earthquake is especially challenging, since there is little warning, an inability to predict potential scale of impairment of mental health services, and a loss of broad infrastructure," the authors wrote.

They noted that their sample was relatively small, but with appropriate support and monitoring, such plans could help to minimize the negative mental health consequences of disasters in larger communities.

SAN ANTONIO – Teaching older adults how to solve some of the challenging problems in their lives can help ease or lift the burden of late-life depression, Patricia A. Areán, Ph.D., reported at the annual meeting of the American Association for Geriatric Psychiatry.

People with poor problem-solving skills might be susceptible to depression, and life problems such as death of a spouse, financial worries, or health concerns such as disability can help trigger depression, said Dr. Areán, a licensed clinical psychologist and professor of psychiatry at the University of California, San Francisco.

But with problem-solving therapy (PST), patients can feel that they are in control of at least some aspect of their lives and work with the therapist to find practical solutions to challenging problems.

Although it is similar to cognitive-behavioral therapy, in PST the therapist focuses on "teaching a set of skills to walk patients through problems they encounter in a systematic way," Dr. Areán said.

PST helps patients better manage their lives. With fewer problems, their self-reliance is enhanced, often leading to increased optimism and improved mood. When patients have learned how to more effectively solve problems, the skills can help to prevent further bouts of depression, she said.

The technique has been shown to be effective among community-dwelling older adults, primary care patients, homebound and disabled elderly, and older adults with treatment-resistant late-life depression. It can be performed in the setting that’s most comfortable or convenient for the patient, whether that’s "on the phone, office, home, Skype, whatever," she said.

Seven steps are essential to PST. The therapist:

• Orients the patient to the therapy and helps clarify and define the problem;

• Helps the patient set realistic goals and expectations;

• Works with the patient to "brainstorm" multiple potential solutions;

• Helps the patient evaluate and compare the proposed solutions;

• Works with the patient to select a feasible solution;

• Helps to implement the solution; and

• Evaluates the outcome.

The program consists of 12 hour-long sessions dedicated to solving a particular problem, reviewing problem-solving skills, and discussing additional problems to solve between sessions. The goal is to enable the patient to eventually solve problems on his or her own.

The first session focuses on socializing the patient to the therapy, discussing depression, giving a broad outline of PST, and providing a therapy frame. The patient and therapist then compile a brief problem list, using a worksheet that allows them to list a problem with 5 to 10 potential solutions, and to weigh the pros and cons of each.

"Start with the easiest problem first," Dr. Areán said. If the patient wants to tell his or her story, the therapist should patiently but firmly direct the discussion back toward the problem at hand.

In the remaining sessions, the patient is asked to consider whether each proposed solution meets immediate and/or long-term goals, might create other problems, and is feasible. The patient can then choose the solution that has the right combination of most pros and fewest cons, is the most workable, and requires the least amount of effort.

The process includes a solution evaluation follow-up to discuss whether the solution worked, and if it did, why. If the solution did not work, then the follow-up discusses what the patient learned, and whether he or she has considered if the problem needs to be redefined.

It also is important that patients take some time during their problem-solving to include pleasant activities and reward for their hard work. The therapist, in turn, should reinforce the patient’s efforts at change, Dr. Areán said.

PST is versatile, with a brief but structured format that lends itself to multiple settings and cultural groups, and can be easily learned by clinicians at PST "hubs" throughout the United States, she concluded.

Dr. Areán reported no conflicts of interest.

SAN ANTONIO – Teaching older adults how to solve some of the challenging problems in their lives can help ease or lift the burden of late-life depression, Patricia A. Areán, Ph.D., reported at the annual meeting of the American Association for Geriatric Psychiatry.

People with poor problem-solving skills might be susceptible to depression, and life problems such as death of a spouse, financial worries, or health concerns such as disability can help trigger depression, said Dr. Areán, a licensed clinical psychologist and professor of psychiatry at the University of California, San Francisco.

But with problem-solving therapy (PST), patients can feel that they are in control of at least some aspect of their lives and work with the therapist to find practical solutions to challenging problems.

Although it is similar to cognitive-behavioral therapy, in PST the therapist focuses on "teaching a set of skills to walk patients through problems they encounter in a systematic way," Dr. Areán said.

PST helps patients better manage their lives. With fewer problems, their self-reliance is enhanced, often leading to increased optimism and improved mood. When patients have learned how to more effectively solve problems, the skills can help to prevent further bouts of depression, she said.

The technique has been shown to be effective among community-dwelling older adults, primary care patients, homebound and disabled elderly, and older adults with treatment-resistant late-life depression. It can be performed in the setting that’s most comfortable or convenient for the patient, whether that’s "on the phone, office, home, Skype, whatever," she said.

Seven steps are essential to PST. The therapist:

• Orients the patient to the therapy and helps clarify and define the problem;

• Helps the patient set realistic goals and expectations;

• Works with the patient to "brainstorm" multiple potential solutions;

• Helps the patient evaluate and compare the proposed solutions;

• Works with the patient to select a feasible solution;

• Helps to implement the solution; and

• Evaluates the outcome.

The program consists of 12 hour-long sessions dedicated to solving a particular problem, reviewing problem-solving skills, and discussing additional problems to solve between sessions. The goal is to enable the patient to eventually solve problems on his or her own.

The first session focuses on socializing the patient to the therapy, discussing depression, giving a broad outline of PST, and providing a therapy frame. The patient and therapist then compile a brief problem list, using a worksheet that allows them to list a problem with 5 to 10 potential solutions, and to weigh the pros and cons of each.

"Start with the easiest problem first," Dr. Areán said. If the patient wants to tell his or her story, the therapist should patiently but firmly direct the discussion back toward the problem at hand.

In the remaining sessions, the patient is asked to consider whether each proposed solution meets immediate and/or long-term goals, might create other problems, and is feasible. The patient can then choose the solution that has the right combination of most pros and fewest cons, is the most workable, and requires the least amount of effort.

The process includes a solution evaluation follow-up to discuss whether the solution worked, and if it did, why. If the solution did not work, then the follow-up discusses what the patient learned, and whether he or she has considered if the problem needs to be redefined.

It also is important that patients take some time during their problem-solving to include pleasant activities and reward for their hard work. The therapist, in turn, should reinforce the patient’s efforts at change, Dr. Areán said.

PST is versatile, with a brief but structured format that lends itself to multiple settings and cultural groups, and can be easily learned by clinicians at PST "hubs" throughout the United States, she concluded.

Dr. Areán reported no conflicts of interest.

SAN ANTONIO – Teaching older adults how to solve some of the challenging problems in their lives can help ease or lift the burden of late-life depression, Patricia A. Areán, Ph.D., reported at the annual meeting of the American Association for Geriatric Psychiatry.

People with poor problem-solving skills might be susceptible to depression, and life problems such as death of a spouse, financial worries, or health concerns such as disability can help trigger depression, said Dr. Areán, a licensed clinical psychologist and professor of psychiatry at the University of California, San Francisco.

But with problem-solving therapy (PST), patients can feel that they are in control of at least some aspect of their lives and work with the therapist to find practical solutions to challenging problems.

Although it is similar to cognitive-behavioral therapy, in PST the therapist focuses on "teaching a set of skills to walk patients through problems they encounter in a systematic way," Dr. Areán said.

PST helps patients better manage their lives. With fewer problems, their self-reliance is enhanced, often leading to increased optimism and improved mood. When patients have learned how to more effectively solve problems, the skills can help to prevent further bouts of depression, she said.

The technique has been shown to be effective among community-dwelling older adults, primary care patients, homebound and disabled elderly, and older adults with treatment-resistant late-life depression. It can be performed in the setting that’s most comfortable or convenient for the patient, whether that’s "on the phone, office, home, Skype, whatever," she said.

Seven steps are essential to PST. The therapist:

• Orients the patient to the therapy and helps clarify and define the problem;

• Helps the patient set realistic goals and expectations;

• Works with the patient to "brainstorm" multiple potential solutions;

• Helps the patient evaluate and compare the proposed solutions;

• Works with the patient to select a feasible solution;

• Helps to implement the solution; and

• Evaluates the outcome.

The program consists of 12 hour-long sessions dedicated to solving a particular problem, reviewing problem-solving skills, and discussing additional problems to solve between sessions. The goal is to enable the patient to eventually solve problems on his or her own.

The first session focuses on socializing the patient to the therapy, discussing depression, giving a broad outline of PST, and providing a therapy frame. The patient and therapist then compile a brief problem list, using a worksheet that allows them to list a problem with 5 to 10 potential solutions, and to weigh the pros and cons of each.

"Start with the easiest problem first," Dr. Areán said. If the patient wants to tell his or her story, the therapist should patiently but firmly direct the discussion back toward the problem at hand.

In the remaining sessions, the patient is asked to consider whether each proposed solution meets immediate and/or long-term goals, might create other problems, and is feasible. The patient can then choose the solution that has the right combination of most pros and fewest cons, is the most workable, and requires the least amount of effort.

The process includes a solution evaluation follow-up to discuss whether the solution worked, and if it did, why. If the solution did not work, then the follow-up discusses what the patient learned, and whether he or she has considered if the problem needs to be redefined.

It also is important that patients take some time during their problem-solving to include pleasant activities and reward for their hard work. The therapist, in turn, should reinforce the patient’s efforts at change, Dr. Areán said.

PST is versatile, with a brief but structured format that lends itself to multiple settings and cultural groups, and can be easily learned by clinicians at PST "hubs" throughout the United States, she concluded.

Dr. Areán reported no conflicts of interest.

SAN ANTONIO – Teaching older adults how to solve some of the challenging problems in their lives can help ease or lift the burden of late-life depression, Patricia A. Areán, Ph.D., reported at the annual meeting of the American Association for Geriatric Psychiatry.

People with poor problem-solving skills might be susceptible to depression, and life problems such as death of a spouse, financial worries, or health concerns such as disability can help trigger depression, said Dr. Areán, a licensed clinical psychologist and professor of psychiatry at the University of California, San Francisco.

But with problem-solving therapy (PST), patients can feel that they are in control of at least some aspect of their lives and work with the therapist to find practical solutions to challenging problems.

Although it is similar to cognitive-behavioral therapy, in PST the therapist focuses on "teaching a set of skills to walk patients through problems they encounter in a systematic way," Dr. Areán said.

PST helps patients better manage their lives. With fewer problems, their self-reliance is enhanced, often leading to increased optimism and improved mood. When patients have learned how to more effectively solve problems, the skills can help to prevent further bouts of depression, she said.

The technique has been shown to be effective among community-dwelling older adults, primary care patients, homebound and disabled elderly, and older adults with treatment-resistant late-life depression. It can be performed in the setting that’s most comfortable or convenient for the patient, whether that’s "on the phone, office, home, Skype, whatever," she said.

Seven steps are essential to PST. The therapist:

• Orients the patient to the therapy and helps clarify and define the problem;

• Helps the patient set realistic goals and expectations;

• Works with the patient to "brainstorm" multiple potential solutions;

• Helps the patient evaluate and compare the proposed solutions;

• Works with the patient to select a feasible solution;

• Helps to implement the solution; and

• Evaluates the outcome.

The program consists of 12 hour-long sessions dedicated to solving a particular problem, reviewing problem-solving skills, and discussing additional problems to solve between sessions. The goal is to enable the patient to eventually solve problems on his or her own.

The first session focuses on socializing the patient to the therapy, discussing depression, giving a broad outline of PST, and providing a therapy frame. The patient and therapist then compile a brief problem list, using a worksheet that allows them to list a problem with 5 to 10 potential solutions, and to weigh the pros and cons of each.

"Start with the easiest problem first," Dr. Areán said. If the patient wants to tell his or her story, the therapist should patiently but firmly direct the discussion back toward the problem at hand.

In the remaining sessions, the patient is asked to consider whether each proposed solution meets immediate and/or long-term goals, might create other problems, and is feasible. The patient can then choose the solution that has the right combination of most pros and fewest cons, is the most workable, and requires the least amount of effort.

The process includes a solution evaluation follow-up to discuss whether the solution worked, and if it did, why. If the solution did not work, then the follow-up discusses what the patient learned, and whether he or she has considered if the problem needs to be redefined.

It also is important that patients take some time during their problem-solving to include pleasant activities and reward for their hard work. The therapist, in turn, should reinforce the patient’s efforts at change, Dr. Areán said.

PST is versatile, with a brief but structured format that lends itself to multiple settings and cultural groups, and can be easily learned by clinicians at PST "hubs" throughout the United States, she concluded.

Dr. Areán reported no conflicts of interest.

SAN ANTONIO – Teaching older adults how to solve some of the challenging problems in their lives can help ease or lift the burden of late-life depression, Patricia A. Areán, Ph.D., reported at the annual meeting of the American Association for Geriatric Psychiatry.

People with poor problem-solving skills might be susceptible to depression, and life problems such as death of a spouse, financial worries, or health concerns such as disability can help trigger depression, said Dr. Areán, a licensed clinical psychologist and professor of psychiatry at the University of California, San Francisco.

But with problem-solving therapy (PST), patients can feel that they are in control of at least some aspect of their lives and work with the therapist to find practical solutions to challenging problems.

Although it is similar to cognitive-behavioral therapy, in PST the therapist focuses on "teaching a set of skills to walk patients through problems they encounter in a systematic way," Dr. Areán said.

PST helps patients better manage their lives. With fewer problems, their self-reliance is enhanced, often leading to increased optimism and improved mood. When patients have learned how to more effectively solve problems, the skills can help to prevent further bouts of depression, she said.

The technique has been shown to be effective among community-dwelling older adults, primary care patients, homebound and disabled elderly, and older adults with treatment-resistant late-life depression. It can be performed in the setting that’s most comfortable or convenient for the patient, whether that’s "on the phone, office, home, Skype, whatever," she said.

Seven steps are essential to PST. The therapist:

• Orients the patient to the therapy and helps clarify and define the problem;

• Helps the patient set realistic goals and expectations;

• Works with the patient to "brainstorm" multiple potential solutions;

• Helps the patient evaluate and compare the proposed solutions;

• Works with the patient to select a feasible solution;

• Helps to implement the solution; and

• Evaluates the outcome.

The program consists of 12 hour-long sessions dedicated to solving a particular problem, reviewing problem-solving skills, and discussing additional problems to solve between sessions. The goal is to enable the patient to eventually solve problems on his or her own.

The first session focuses on socializing the patient to the therapy, discussing depression, giving a broad outline of PST, and providing a therapy frame. The patient and therapist then compile a brief problem list, using a worksheet that allows them to list a problem with 5 to 10 potential solutions, and to weigh the pros and cons of each.

"Start with the easiest problem first," Dr. Areán said. If the patient wants to tell his or her story, the therapist should patiently but firmly direct the discussion back toward the problem at hand.

In the remaining sessions, the patient is asked to consider whether each proposed solution meets immediate and/or long-term goals, might create other problems, and is feasible. The patient can then choose the solution that has the right combination of most pros and fewest cons, is the most workable, and requires the least amount of effort.

The process includes a solution evaluation follow-up to discuss whether the solution worked, and if it did, why. If the solution did not work, then the follow-up discusses what the patient learned, and whether he or she has considered if the problem needs to be redefined.

It also is important that patients take some time during their problem-solving to include pleasant activities and reward for their hard work. The therapist, in turn, should reinforce the patient’s efforts at change, Dr. Areán said.

PST is versatile, with a brief but structured format that lends itself to multiple settings and cultural groups, and can be easily learned by clinicians at PST "hubs" throughout the United States, she concluded.

Dr. Areán reported no conflicts of interest.

SAN ANTONIO – Teaching older adults how to solve some of the challenging problems in their lives can help ease or lift the burden of late-life depression, Patricia A. Areán, Ph.D., reported at the annual meeting of the American Association for Geriatric Psychiatry.

People with poor problem-solving skills might be susceptible to depression, and life problems such as death of a spouse, financial worries, or health concerns such as disability can help trigger depression, said Dr. Areán, a licensed clinical psychologist and professor of psychiatry at the University of California, San Francisco.

But with problem-solving therapy (PST), patients can feel that they are in control of at least some aspect of their lives and work with the therapist to find practical solutions to challenging problems.

Although it is similar to cognitive-behavioral therapy, in PST the therapist focuses on "teaching a set of skills to walk patients through problems they encounter in a systematic way," Dr. Areán said.

PST helps patients better manage their lives. With fewer problems, their self-reliance is enhanced, often leading to increased optimism and improved mood. When patients have learned how to more effectively solve problems, the skills can help to prevent further bouts of depression, she said.

The technique has been shown to be effective among community-dwelling older adults, primary care patients, homebound and disabled elderly, and older adults with treatment-resistant late-life depression. It can be performed in the setting that’s most comfortable or convenient for the patient, whether that’s "on the phone, office, home, Skype, whatever," she said.

Seven steps are essential to PST. The therapist:

• Orients the patient to the therapy and helps clarify and define the problem;

• Helps the patient set realistic goals and expectations;

• Works with the patient to "brainstorm" multiple potential solutions;

• Helps the patient evaluate and compare the proposed solutions;

• Works with the patient to select a feasible solution;

• Helps to implement the solution; and

• Evaluates the outcome.

The program consists of 12 hour-long sessions dedicated to solving a particular problem, reviewing problem-solving skills, and discussing additional problems to solve between sessions. The goal is to enable the patient to eventually solve problems on his or her own.

The first session focuses on socializing the patient to the therapy, discussing depression, giving a broad outline of PST, and providing a therapy frame. The patient and therapist then compile a brief problem list, using a worksheet that allows them to list a problem with 5 to 10 potential solutions, and to weigh the pros and cons of each.

"Start with the easiest problem first," Dr. Areán said. If the patient wants to tell his or her story, the therapist should patiently but firmly direct the discussion back toward the problem at hand.

In the remaining sessions, the patient is asked to consider whether each proposed solution meets immediate and/or long-term goals, might create other problems, and is feasible. The patient can then choose the solution that has the right combination of most pros and fewest cons, is the most workable, and requires the least amount of effort.

The process includes a solution evaluation follow-up to discuss whether the solution worked, and if it did, why. If the solution did not work, then the follow-up discusses what the patient learned, and whether he or she has considered if the problem needs to be redefined.

It also is important that patients take some time during their problem-solving to include pleasant activities and reward for their hard work. The therapist, in turn, should reinforce the patient’s efforts at change, Dr. Areán said.

PST is versatile, with a brief but structured format that lends itself to multiple settings and cultural groups, and can be easily learned by clinicians at PST "hubs" throughout the United States, she concluded.

Dr. Areán reported no conflicts of interest.

SAN ANTONIO – Teaching older adults how to solve some of the challenging problems in their lives can help ease or lift the burden of late-life depression, Patricia A. Areán, Ph.D., reported at the annual meeting of the American Association for Geriatric Psychiatry.

People with poor problem-solving skills might be susceptible to depression, and life problems such as death of a spouse, financial worries, or health concerns such as disability can help trigger depression, said Dr. Areán, a licensed clinical psychologist and professor of psychiatry at the University of California, San Francisco.

But with problem-solving therapy (PST), patients can feel that they are in control of at least some aspect of their lives and work with the therapist to find practical solutions to challenging problems.

Although it is similar to cognitive-behavioral therapy, in PST the therapist focuses on "teaching a set of skills to walk patients through problems they encounter in a systematic way," Dr. Areán said.

PST helps patients better manage their lives. With fewer problems, their self-reliance is enhanced, often leading to increased optimism and improved mood. When patients have learned how to more effectively solve problems, the skills can help to prevent further bouts of depression, she said.

The technique has been shown to be effective among community-dwelling older adults, primary care patients, homebound and disabled elderly, and older adults with treatment-resistant late-life depression. It can be performed in the setting that’s most comfortable or convenient for the patient, whether that’s "on the phone, office, home, Skype, whatever," she said.

Seven steps are essential to PST. The therapist:

• Orients the patient to the therapy and helps clarify and define the problem;

• Helps the patient set realistic goals and expectations;

• Works with the patient to "brainstorm" multiple potential solutions;

• Helps the patient evaluate and compare the proposed solutions;

• Works with the patient to select a feasible solution;

• Helps to implement the solution; and

• Evaluates the outcome.

The program consists of 12 hour-long sessions dedicated to solving a particular problem, reviewing problem-solving skills, and discussing additional problems to solve between sessions. The goal is to enable the patient to eventually solve problems on his or her own.

The first session focuses on socializing the patient to the therapy, discussing depression, giving a broad outline of PST, and providing a therapy frame. The patient and therapist then compile a brief problem list, using a worksheet that allows them to list a problem with 5 to 10 potential solutions, and to weigh the pros and cons of each.

"Start with the easiest problem first," Dr. Areán said. If the patient wants to tell his or her story, the therapist should patiently but firmly direct the discussion back toward the problem at hand.

In the remaining sessions, the patient is asked to consider whether each proposed solution meets immediate and/or long-term goals, might create other problems, and is feasible. The patient can then choose the solution that has the right combination of most pros and fewest cons, is the most workable, and requires the least amount of effort.

The process includes a solution evaluation follow-up to discuss whether the solution worked, and if it did, why. If the solution did not work, then the follow-up discusses what the patient learned, and whether he or she has considered if the problem needs to be redefined.

It also is important that patients take some time during their problem-solving to include pleasant activities and reward for their hard work. The therapist, in turn, should reinforce the patient’s efforts at change, Dr. Areán said.

PST is versatile, with a brief but structured format that lends itself to multiple settings and cultural groups, and can be easily learned by clinicians at PST "hubs" throughout the United States, she concluded.

Dr. Areán reported no conflicts of interest.

SAN ANTONIO – Teaching older adults how to solve some of the challenging problems in their lives can help ease or lift the burden of late-life depression, Patricia A. Areán, Ph.D., reported at the annual meeting of the American Association for Geriatric Psychiatry.

People with poor problem-solving skills might be susceptible to depression, and life problems such as death of a spouse, financial worries, or health concerns such as disability can help trigger depression, said Dr. Areán, a licensed clinical psychologist and professor of psychiatry at the University of California, San Francisco.

But with problem-solving therapy (PST), patients can feel that they are in control of at least some aspect of their lives and work with the therapist to find practical solutions to challenging problems.

Although it is similar to cognitive-behavioral therapy, in PST the therapist focuses on "teaching a set of skills to walk patients through problems they encounter in a systematic way," Dr. Areán said.

PST helps patients better manage their lives. With fewer problems, their self-reliance is enhanced, often leading to increased optimism and improved mood. When patients have learned how to more effectively solve problems, the skills can help to prevent further bouts of depression, she said.

The technique has been shown to be effective among community-dwelling older adults, primary care patients, homebound and disabled elderly, and older adults with treatment-resistant late-life depression. It can be performed in the setting that’s most comfortable or convenient for the patient, whether that’s "on the phone, office, home, Skype, whatever," she said.

Seven steps are essential to PST. The therapist:

• Orients the patient to the therapy and helps clarify and define the problem;

• Helps the patient set realistic goals and expectations;

• Works with the patient to "brainstorm" multiple potential solutions;

• Helps the patient evaluate and compare the proposed solutions;

• Works with the patient to select a feasible solution;

• Helps to implement the solution; and

• Evaluates the outcome.

The program consists of 12 hour-long sessions dedicated to solving a particular problem, reviewing problem-solving skills, and discussing additional problems to solve between sessions. The goal is to enable the patient to eventually solve problems on his or her own.

The first session focuses on socializing the patient to the therapy, discussing depression, giving a broad outline of PST, and providing a therapy frame. The patient and therapist then compile a brief problem list, using a worksheet that allows them to list a problem with 5 to 10 potential solutions, and to weigh the pros and cons of each.

"Start with the easiest problem first," Dr. Areán said. If the patient wants to tell his or her story, the therapist should patiently but firmly direct the discussion back toward the problem at hand.

In the remaining sessions, the patient is asked to consider whether each proposed solution meets immediate and/or long-term goals, might create other problems, and is feasible. The patient can then choose the solution that has the right combination of most pros and fewest cons, is the most workable, and requires the least amount of effort.

The process includes a solution evaluation follow-up to discuss whether the solution worked, and if it did, why. If the solution did not work, then the follow-up discusses what the patient learned, and whether he or she has considered if the problem needs to be redefined.

It also is important that patients take some time during their problem-solving to include pleasant activities and reward for their hard work. The therapist, in turn, should reinforce the patient’s efforts at change, Dr. Areán said.

PST is versatile, with a brief but structured format that lends itself to multiple settings and cultural groups, and can be easily learned by clinicians at PST "hubs" throughout the United States, she concluded.

Dr. Areán reported no conflicts of interest.

SAN ANTONIO – Teaching older adults how to solve some of the challenging problems in their lives can help ease or lift the burden of late-life depression, Patricia A. Areán, Ph.D., reported at the annual meeting of the American Association for Geriatric Psychiatry.

People with poor problem-solving skills might be susceptible to depression, and life problems such as death of a spouse, financial worries, or health concerns such as disability can help trigger depression, said Dr. Areán, a licensed clinical psychologist and professor of psychiatry at the University of California, San Francisco.

But with problem-solving therapy (PST), patients can feel that they are in control of at least some aspect of their lives and work with the therapist to find practical solutions to challenging problems.

Although it is similar to cognitive-behavioral therapy, in PST the therapist focuses on "teaching a set of skills to walk patients through problems they encounter in a systematic way," Dr. Areán said.

PST helps patients better manage their lives. With fewer problems, their self-reliance is enhanced, often leading to increased optimism and improved mood. When patients have learned how to more effectively solve problems, the skills can help to prevent further bouts of depression, she said.

The technique has been shown to be effective among community-dwelling older adults, primary care patients, homebound and disabled elderly, and older adults with treatment-resistant late-life depression. It can be performed in the setting that’s most comfortable or convenient for the patient, whether that’s "on the phone, office, home, Skype, whatever," she said.

Seven steps are essential to PST. The therapist:

• Orients the patient to the therapy and helps clarify and define the problem;

• Helps the patient set realistic goals and expectations;

• Works with the patient to "brainstorm" multiple potential solutions;

• Helps the patient evaluate and compare the proposed solutions;

• Works with the patient to select a feasible solution;

• Helps to implement the solution; and

• Evaluates the outcome.

The program consists of 12 hour-long sessions dedicated to solving a particular problem, reviewing problem-solving skills, and discussing additional problems to solve between sessions. The goal is to enable the patient to eventually solve problems on his or her own.

The first session focuses on socializing the patient to the therapy, discussing depression, giving a broad outline of PST, and providing a therapy frame. The patient and therapist then compile a brief problem list, using a worksheet that allows them to list a problem with 5 to 10 potential solutions, and to weigh the pros and cons of each.

"Start with the easiest problem first," Dr. Areán said. If the patient wants to tell his or her story, the therapist should patiently but firmly direct the discussion back toward the problem at hand.

In the remaining sessions, the patient is asked to consider whether each proposed solution meets immediate and/or long-term goals, might create other problems, and is feasible. The patient can then choose the solution that has the right combination of most pros and fewest cons, is the most workable, and requires the least amount of effort.

The process includes a solution evaluation follow-up to discuss whether the solution worked, and if it did, why. If the solution did not work, then the follow-up discusses what the patient learned, and whether he or she has considered if the problem needs to be redefined.

It also is important that patients take some time during their problem-solving to include pleasant activities and reward for their hard work. The therapist, in turn, should reinforce the patient’s efforts at change, Dr. Areán said.

PST is versatile, with a brief but structured format that lends itself to multiple settings and cultural groups, and can be easily learned by clinicians at PST "hubs" throughout the United States, she concluded.

Dr. Areán reported no conflicts of interest.

BOSTON – Active surveillance testing for methicillin-resistant Staphylococcus aureus colonization of pregnant women who were admitted to labor and delivery units costs a lot of bucks for only a little bang.

Over a 20-month period, a universal methicillin-resistant S. aureus (MRSA) screening program, required by Illinois law, cost $90,950 but had no apparent impact either on MRSA disease in the postpartum period or on nosocomial MRSA infections in a postpartum ward and newborn nursery, said Naseem Helo, a fourth-year medical student at Loyola University Medical Center in Maywood, Ill.

Among 2,254 pregnant women who were admitted to the labor and delivery unit, 1,819 (81%) received a nasal MRSA test at a cost of $50 each and 39 women (2%) screened positive, for a cost of more than $2,300 per positive screen, Mr. Helo said at the meeting, which was sponsored by the American Society for Microbiology.

Of the 39 MRSA-colonized women, 13 went on to have a cesarean section, 21 had vaginal delivery, 2 had miscarriages, and 3 were lost to follow-up because they did not deliver at the center.

When investigators looked at the effect of the positive results on practice, they found that although 9 of 13 (69%) women who had cesareans had positive test results available before the surgery, only 3 of the 9 (33%) received vancomycin prophylaxis.

“During the newborn stay, no newborns had complications of MRSA disease, and there were no nosocomial infections in our labor and delivery service, postpartum ward, and newborn nursery during the 20-month study period or 2 years prior to the study,” Mr. Helo said.

The investigators suggested that the decision to implement universal MRSA surveillance should be driven by MRSA colonization rates in specific geographic populations.

BOSTON – Active surveillance testing for methicillin-resistant Staphylococcus aureus colonization of pregnant women who were admitted to labor and delivery units costs a lot of bucks for only a little bang.

Over a 20-month period, a universal methicillin-resistant S. aureus (MRSA) screening program, required by Illinois law, cost $90,950 but had no apparent impact either on MRSA disease in the postpartum period or on nosocomial MRSA infections in a postpartum ward and newborn nursery, said Naseem Helo, a fourth-year medical student at Loyola University Medical Center in Maywood, Ill.

Among 2,254 pregnant women who were admitted to the labor and delivery unit, 1,819 (81%) received a nasal MRSA test at a cost of $50 each and 39 women (2%) screened positive, for a cost of more than $2,300 per positive screen, Mr. Helo said at the meeting, which was sponsored by the American Society for Microbiology.

Of the 39 MRSA-colonized women, 13 went on to have a cesarean section, 21 had vaginal delivery, 2 had miscarriages, and 3 were lost to follow-up because they did not deliver at the center.

When investigators looked at the effect of the positive results on practice, they found that although 9 of 13 (69%) women who had cesareans had positive test results available before the surgery, only 3 of the 9 (33%) received vancomycin prophylaxis.

“During the newborn stay, no newborns had complications of MRSA disease, and there were no nosocomial infections in our labor and delivery service, postpartum ward, and newborn nursery during the 20-month study period or 2 years prior to the study,” Mr. Helo said.

The investigators suggested that the decision to implement universal MRSA surveillance should be driven by MRSA colonization rates in specific geographic populations.

BOSTON – Active surveillance testing for methicillin-resistant Staphylococcus aureus colonization of pregnant women who were admitted to labor and delivery units costs a lot of bucks for only a little bang.

Over a 20-month period, a universal methicillin-resistant S. aureus (MRSA) screening program, required by Illinois law, cost $90,950 but had no apparent impact either on MRSA disease in the postpartum period or on nosocomial MRSA infections in a postpartum ward and newborn nursery, said Naseem Helo, a fourth-year medical student at Loyola University Medical Center in Maywood, Ill.

Among 2,254 pregnant women who were admitted to the labor and delivery unit, 1,819 (81%) received a nasal MRSA test at a cost of $50 each and 39 women (2%) screened positive, for a cost of more than $2,300 per positive screen, Mr. Helo said at the meeting, which was sponsored by the American Society for Microbiology.

Of the 39 MRSA-colonized women, 13 went on to have a cesarean section, 21 had vaginal delivery, 2 had miscarriages, and 3 were lost to follow-up because they did not deliver at the center.

When investigators looked at the effect of the positive results on practice, they found that although 9 of 13 (69%) women who had cesareans had positive test results available before the surgery, only 3 of the 9 (33%) received vancomycin prophylaxis.

“During the newborn stay, no newborns had complications of MRSA disease, and there were no nosocomial infections in our labor and delivery service, postpartum ward, and newborn nursery during the 20-month study period or 2 years prior to the study,” Mr. Helo said.

The investigators suggested that the decision to implement universal MRSA surveillance should be driven by MRSA colonization rates in specific geographic populations.

Cancer therapeutic vaccines can seem like the smartest but laziest kid in the class: always showing promise, but largely failing to live up to their potential.

Despite several flameouts in recent years – notably, a failed trial for a nonspecific therapeutic vaccine for prostate cancer using the GVAX platform, and the tanking of two different approaches to vaccinating patients against malignant melanoma – the pace of vaccine research seems to have quickened.

A search for "cancer therapeutic vaccine" on ClinicalTrials.gov shows more than 100 studies that are either recruiting or in active planning. BioSante Pharmaceuticals alone has 15 phase I and phase II clinical studies involving vaccines based on the GVAX platform against acute and chronic myeloid leukemias, breast cancer, pancreatic cancer, and other tumors.

Is this, as Samuel Johnson said of second marriages, the triumph of hope over experience? Not so, say leading vaccine researchers. Indeed, vaccine development is flourishing, in large measure because of the lessons learned from earlier defeats, and it got a shot in the arm with the approval last year of sipuleucel-T (Provenge) as the first cancer therapeutic vaccine.

"Basic immunology – such as the relationship between a growing cancer and the host immune response – is becoming better understood. We also understand better how to vaccinate. There were some vaccines that went forward because they were doable, and not necessarily because they were ideal or optimized," said Dr. Thomas F. Gajewski, president of the International Society for Biological Therapy of Cancer.

Helping the Immune System Help Itself

The concept of therapeutic vaccines is tantalizing: Give the patient the right antigen, delivered with a suitable adjuvant, and you can train the immune system to recognize malignant cells as foreign.

In contrast, other types of immunotherapeutic agents – such as rituximab (Rituxan), trastuzumab (Herceptin), and ipilimumab (Yervoy) – are monoclonal antibodies that are directed against specific cellular targets: the CD20 receptor on B cells in the case of rituximab, the HER2 protein in cancer cells for trastuzumab, and the CTLA-4 surface antigen on T cells for ipilimumab.

Ipilimumab, which is delivered with a peptide vaccine to enhance immune response, was the first agent to demonstrate a survival advantage in phase III, randomized trials for patients with malignant melanoma (with peptide vaccine alone as the comparator), and it could receive Food and Drug Administration approval this month.

But not all cancers share the same targets, and marshalling the body’s defenses against melanoma in particular is a good bit trickier than getting it to raise antibodies against polio or smallpox, investigators say. A history of setbacks proves it.

For example, at the 2007 annual meeting of the American Society of Clinical Oncology, investigators in the MMAIT (Malignant Melanoma Active Immunotherapy Trial) reported that patients with resected metastatic, stage III or stage IV melanoma gained no overall benefit from a combination of BCG (bacille Calmette-Guérin) and allogeneic melanoma vaccine (Canvaxin).

Similarly, at ASCO 2008, investigators in the phase III EORTC (European Organisation for Research and Treatment of Cancer) 18961 trial reported that an adjuvant vaccine that was targeted against a ganglioside that was overexpressed on most melanoma cells did not improve distant metastasis-free survival, and that an early interim analysis suggested a detriment to overall survival. (Subsequent analyses have suggested that earlier fears of harm from the vaccine may have been unwarranted, however.)

Antibodies Not Up to the Task

The goal of current therapeutic vaccines is to generate a cytotoxic T-cell response, primarily with CD8-positive effector T cells, something that has not been achieved with conventional vaccines that are primarily designed to induce antibodies.

"In most solid tumors, those antibodies are not going to be enough; they probably won’t hurt, but they’re not sufficient, and you need the T-cell response to get real tumor-cell killing," said Dr. Gajewski, a professor of pathology and medicine in the section of hematology/oncology at the University of Chicago.

GVAX in its earlier incarnation fell short of the mark because – unlike sipuleucel-T, which is an autologous vaccine comprising transduced prostatic acid phosphotase cells unique to each patient – GVAX was not specific to the tumor characteristics of individual patients, Dr. Gajewski noted.

"GVAX was an allogeneic vaccine transduced to express granulocyte-macrophage colony stimulating factor [GM-CSF], and that way you only have to express the molecule in one cell line, and then you try to administer it to all the patients hoping that there’s enough in common that they induce the immune response that recognizes the tumor in that patient. That’s true in some cases; in other cases, it’s not," he added.

"The main lesson learned in the prostate cancer trials is that the stage of cancer is critical to the success of a cancer vaccine," said BioSante president and chief executive officer Stephen Simes in an e-mail interview. "Those men who had a predicted survival (Halabi score) of 18 months or more received a benefit from the cancer vaccine, but those with a predicted survival [of less than] 18 months did not. Overall, the mean predicted survival of the men in the prostate studies was 13-16 months, hence the less-than-positive outcome. ... The men in the Provenge trials had a predicted survival of 21 months before therapy, and hence the better outcomes."

The company is finalizing a regulatory submission to remove a clinical hold on the prostate cancer vaccine, and it plans to start an open-label, phase II trial of a neoadjuvant vaccine combined with an immune checkpoint regulatory molecule. The trial will enroll patients who have a lower disease burden than do those in the previous prostate cancer vaccine trials, according to Mr. Simes.

The failed European antimelanoma vaccine trial tested the hypothesis that raising antibodies to a cell-surface component (ganglioside) could result in an antitumor effect, but "we have no good data in melanoma that antibodies against surface markers are good for very much. That’s not the mechanism the host response uses to kill tumors when it is successful," Dr. Gajewski said.

Therapeutic vaccine developers are also challenged by the considerable defenses thrown up by tumors themselves, noted Dr. Mario Sznol, vice-chief of medical oncology and codirector of the melanoma program at Yale Cancer Center in New Haven, Conn.

"None of us would expect that vaccines in general would have a very strong effect, because we already know that there are a lot of regulatory checkpoints in T-cell activation that occur beyond the initial immunization, and we know that there are a lot of things that go on in the tumor microenvironment that prevent those T cells from working well there. So while a vaccine might have some activity and be a necessary or adjunctive component to another kind of immune therapy, vaccines by themselves probably would have limited effect," he said.

Dr. Sznol, who investigates methods for overcoming tumor resistance to immune mechanisms, said that vaccines are instead likely to play an adjunctive role in combination with other, more potent immunotherapies, such as ipilimumab or cytokines such as interleukin-2.

"Vaccines might direct the immune system better or contribute to the effect, but looking at it the other way – as the vaccine being the principal component of that immunotherapy – is, I think, the wrong way to look at it," he concluded.

New Platforms, Targets, Challenges

Dr. Gajewski said that the vaccines most likely to succeed are those developed through a stepwise scientific approach, which involves methodical selection of antigens in combination with the adjuvants that produce the optimal cytotoxic T-cell response.

Therapeutic vaccines currently in development use antigens that are derived from proteins, carbohydrates, glycoproteins, glycopeptides, or gangliosides, as well as attenuated tumor-associated antigens that are employed in autologous or allogeneic formulations.

Other strategies include DNA or RNA sequences that code for cancer-associated antigens either delivered singly (naked nucleic acid vaccines) or transfected into viral vectors. Some research teams are focusing on the development of vaccines that are targeted against antigens in specific tumor types, whereas others aim for targets that are common to several different cancer histologies. The latter antigens include MAGE-3 (melanoma-encoding antigen); NY-ESO-1, found in both melanoma and synovial cell sarcoma; and WT-1, the Wilms tumor antigen that is widely expressed in leukemia.

But getting the best cytotoxic T-cell response and incorporating it into off-the-shelf vaccines are only half the battle, Dr. Gajewski said.

"The other half of the equation is whether the tumor and the tumor microenvironment are susceptible to killing by immune cells. Tumor resistance – to the activated immune cells, to cytotoxic T cells, to the effector phase of antitumor immune response – is dominant in many cases" he noted.

Many vaccine researchers are working to develop end runs around the tumor inhibitory pathways that either inactivate T cells when they infiltrate or keep them out of the tumor altogether.

"We have been able to catalog patterns of gene-expression profiling in tumors that correlate positively or negatively with outcomes, and that has identified a set of [biological] processes that seem to represent the barriers [to immunity] at the level of tumor site. And now [that we understand] those, it’s enabling ways to intervene and change the susceptibility of the tumor site to the immune response that’s induced," Dr. Gajewski said.

Dr. Gajewski has received research support for clinical trial participation from Bristol-Myers Squibb, GlaxoSmithKline-Bio, Incyte, Novartis, Eisai, and Genentech/Roche. He has served on advisory boards or served as a paid adviser to Bristol-Myers Squibb, GlaxoSmithKline-Bio, Incyte, Eisai, and Genentech/Roche. Dr. Sznol has received honoraria or served as a consultant to Bristol-Myers Squibb, Genzyme, and Pfizer.

Cancer therapeutic vaccines can seem like the smartest but laziest kid in the class: always showing promise, but largely failing to live up to their potential.

Despite several flameouts in recent years – notably, a failed trial for a nonspecific therapeutic vaccine for prostate cancer using the GVAX platform, and the tanking of two different approaches to vaccinating patients against malignant melanoma – the pace of vaccine research seems to have quickened.

A search for "cancer therapeutic vaccine" on ClinicalTrials.gov shows more than 100 studies that are either recruiting or in active planning. BioSante Pharmaceuticals alone has 15 phase I and phase II clinical studies involving vaccines based on the GVAX platform against acute and chronic myeloid leukemias, breast cancer, pancreatic cancer, and other tumors.

Is this, as Samuel Johnson said of second marriages, the triumph of hope over experience? Not so, say leading vaccine researchers. Indeed, vaccine development is flourishing, in large measure because of the lessons learned from earlier defeats, and it got a shot in the arm with the approval last year of sipuleucel-T (Provenge) as the first cancer therapeutic vaccine.

"Basic immunology – such as the relationship between a growing cancer and the host immune response – is becoming better understood. We also understand better how to vaccinate. There were some vaccines that went forward because they were doable, and not necessarily because they were ideal or optimized," said Dr. Thomas F. Gajewski, president of the International Society for Biological Therapy of Cancer.

Helping the Immune System Help Itself

The concept of therapeutic vaccines is tantalizing: Give the patient the right antigen, delivered with a suitable adjuvant, and you can train the immune system to recognize malignant cells as foreign.

In contrast, other types of immunotherapeutic agents – such as rituximab (Rituxan), trastuzumab (Herceptin), and ipilimumab (Yervoy) – are monoclonal antibodies that are directed against specific cellular targets: the CD20 receptor on B cells in the case of rituximab, the HER2 protein in cancer cells for trastuzumab, and the CTLA-4 surface antigen on T cells for ipilimumab.

Ipilimumab, which is delivered with a peptide vaccine to enhance immune response, was the first agent to demonstrate a survival advantage in phase III, randomized trials for patients with malignant melanoma (with peptide vaccine alone as the comparator), and it could receive Food and Drug Administration approval this month.

But not all cancers share the same targets, and marshalling the body’s defenses against melanoma in particular is a good bit trickier than getting it to raise antibodies against polio or smallpox, investigators say. A history of setbacks proves it.

For example, at the 2007 annual meeting of the American Society of Clinical Oncology, investigators in the MMAIT (Malignant Melanoma Active Immunotherapy Trial) reported that patients with resected metastatic, stage III or stage IV melanoma gained no overall benefit from a combination of BCG (bacille Calmette-Guérin) and allogeneic melanoma vaccine (Canvaxin).

Similarly, at ASCO 2008, investigators in the phase III EORTC (European Organisation for Research and Treatment of Cancer) 18961 trial reported that an adjuvant vaccine that was targeted against a ganglioside that was overexpressed on most melanoma cells did not improve distant metastasis-free survival, and that an early interim analysis suggested a detriment to overall survival. (Subsequent analyses have suggested that earlier fears of harm from the vaccine may have been unwarranted, however.)

Antibodies Not Up to the Task

The goal of current therapeutic vaccines is to generate a cytotoxic T-cell response, primarily with CD8-positive effector T cells, something that has not been achieved with conventional vaccines that are primarily designed to induce antibodies.

"In most solid tumors, those antibodies are not going to be enough; they probably won’t hurt, but they’re not sufficient, and you need the T-cell response to get real tumor-cell killing," said Dr. Gajewski, a professor of pathology and medicine in the section of hematology/oncology at the University of Chicago.

GVAX in its earlier incarnation fell short of the mark because – unlike sipuleucel-T, which is an autologous vaccine comprising transduced prostatic acid phosphotase cells unique to each patient – GVAX was not specific to the tumor characteristics of individual patients, Dr. Gajewski noted.

"GVAX was an allogeneic vaccine transduced to express granulocyte-macrophage colony stimulating factor [GM-CSF], and that way you only have to express the molecule in one cell line, and then you try to administer it to all the patients hoping that there’s enough in common that they induce the immune response that recognizes the tumor in that patient. That’s true in some cases; in other cases, it’s not," he added.

"The main lesson learned in the prostate cancer trials is that the stage of cancer is critical to the success of a cancer vaccine," said BioSante president and chief executive officer Stephen Simes in an e-mail interview. "Those men who had a predicted survival (Halabi score) of 18 months or more received a benefit from the cancer vaccine, but those with a predicted survival [of less than] 18 months did not. Overall, the mean predicted survival of the men in the prostate studies was 13-16 months, hence the less-than-positive outcome. ... The men in the Provenge trials had a predicted survival of 21 months before therapy, and hence the better outcomes."

The company is finalizing a regulatory submission to remove a clinical hold on the prostate cancer vaccine, and it plans to start an open-label, phase II trial of a neoadjuvant vaccine combined with an immune checkpoint regulatory molecule. The trial will enroll patients who have a lower disease burden than do those in the previous prostate cancer vaccine trials, according to Mr. Simes.

The failed European antimelanoma vaccine trial tested the hypothesis that raising antibodies to a cell-surface component (ganglioside) could result in an antitumor effect, but "we have no good data in melanoma that antibodies against surface markers are good for very much. That’s not the mechanism the host response uses to kill tumors when it is successful," Dr. Gajewski said.

Therapeutic vaccine developers are also challenged by the considerable defenses thrown up by tumors themselves, noted Dr. Mario Sznol, vice-chief of medical oncology and codirector of the melanoma program at Yale Cancer Center in New Haven, Conn.

"None of us would expect that vaccines in general would have a very strong effect, because we already know that there are a lot of regulatory checkpoints in T-cell activation that occur beyond the initial immunization, and we know that there are a lot of things that go on in the tumor microenvironment that prevent those T cells from working well there. So while a vaccine might have some activity and be a necessary or adjunctive component to another kind of immune therapy, vaccines by themselves probably would have limited effect," he said.

Dr. Sznol, who investigates methods for overcoming tumor resistance to immune mechanisms, said that vaccines are instead likely to play an adjunctive role in combination with other, more potent immunotherapies, such as ipilimumab or cytokines such as interleukin-2.

"Vaccines might direct the immune system better or contribute to the effect, but looking at it the other way – as the vaccine being the principal component of that immunotherapy – is, I think, the wrong way to look at it," he concluded.

New Platforms, Targets, Challenges

Dr. Gajewski said that the vaccines most likely to succeed are those developed through a stepwise scientific approach, which involves methodical selection of antigens in combination with the adjuvants that produce the optimal cytotoxic T-cell response.

Therapeutic vaccines currently in development use antigens that are derived from proteins, carbohydrates, glycoproteins, glycopeptides, or gangliosides, as well as attenuated tumor-associated antigens that are employed in autologous or allogeneic formulations.

Other strategies include DNA or RNA sequences that code for cancer-associated antigens either delivered singly (naked nucleic acid vaccines) or transfected into viral vectors. Some research teams are focusing on the development of vaccines that are targeted against antigens in specific tumor types, whereas others aim for targets that are common to several different cancer histologies. The latter antigens include MAGE-3 (melanoma-encoding antigen); NY-ESO-1, found in both melanoma and synovial cell sarcoma; and WT-1, the Wilms tumor antigen that is widely expressed in leukemia.

But getting the best cytotoxic T-cell response and incorporating it into off-the-shelf vaccines are only half the battle, Dr. Gajewski said.

"The other half of the equation is whether the tumor and the tumor microenvironment are susceptible to killing by immune cells. Tumor resistance – to the activated immune cells, to cytotoxic T cells, to the effector phase of antitumor immune response – is dominant in many cases" he noted.

Many vaccine researchers are working to develop end runs around the tumor inhibitory pathways that either inactivate T cells when they infiltrate or keep them out of the tumor altogether.

"We have been able to catalog patterns of gene-expression profiling in tumors that correlate positively or negatively with outcomes, and that has identified a set of [biological] processes that seem to represent the barriers [to immunity] at the level of tumor site. And now [that we understand] those, it’s enabling ways to intervene and change the susceptibility of the tumor site to the immune response that’s induced," Dr. Gajewski said.

Dr. Gajewski has received research support for clinical trial participation from Bristol-Myers Squibb, GlaxoSmithKline-Bio, Incyte, Novartis, Eisai, and Genentech/Roche. He has served on advisory boards or served as a paid adviser to Bristol-Myers Squibb, GlaxoSmithKline-Bio, Incyte, Eisai, and Genentech/Roche. Dr. Sznol has received honoraria or served as a consultant to Bristol-Myers Squibb, Genzyme, and Pfizer.

Cancer therapeutic vaccines can seem like the smartest but laziest kid in the class: always showing promise, but largely failing to live up to their potential.

Despite several flameouts in recent years – notably, a failed trial for a nonspecific therapeutic vaccine for prostate cancer using the GVAX platform, and the tanking of two different approaches to vaccinating patients against malignant melanoma – the pace of vaccine research seems to have quickened.

A search for "cancer therapeutic vaccine" on ClinicalTrials.gov shows more than 100 studies that are either recruiting or in active planning. BioSante Pharmaceuticals alone has 15 phase I and phase II clinical studies involving vaccines based on the GVAX platform against acute and chronic myeloid leukemias, breast cancer, pancreatic cancer, and other tumors.

Is this, as Samuel Johnson said of second marriages, the triumph of hope over experience? Not so, say leading vaccine researchers. Indeed, vaccine development is flourishing, in large measure because of the lessons learned from earlier defeats, and it got a shot in the arm with the approval last year of sipuleucel-T (Provenge) as the first cancer therapeutic vaccine.

"Basic immunology – such as the relationship between a growing cancer and the host immune response – is becoming better understood. We also understand better how to vaccinate. There were some vaccines that went forward because they were doable, and not necessarily because they were ideal or optimized," said Dr. Thomas F. Gajewski, president of the International Society for Biological Therapy of Cancer.

Helping the Immune System Help Itself

The concept of therapeutic vaccines is tantalizing: Give the patient the right antigen, delivered with a suitable adjuvant, and you can train the immune system to recognize malignant cells as foreign.

In contrast, other types of immunotherapeutic agents – such as rituximab (Rituxan), trastuzumab (Herceptin), and ipilimumab (Yervoy) – are monoclonal antibodies that are directed against specific cellular targets: the CD20 receptor on B cells in the case of rituximab, the HER2 protein in cancer cells for trastuzumab, and the CTLA-4 surface antigen on T cells for ipilimumab.

Ipilimumab, which is delivered with a peptide vaccine to enhance immune response, was the first agent to demonstrate a survival advantage in phase III, randomized trials for patients with malignant melanoma (with peptide vaccine alone as the comparator), and it could receive Food and Drug Administration approval this month.

But not all cancers share the same targets, and marshalling the body’s defenses against melanoma in particular is a good bit trickier than getting it to raise antibodies against polio or smallpox, investigators say. A history of setbacks proves it.

For example, at the 2007 annual meeting of the American Society of Clinical Oncology, investigators in the MMAIT (Malignant Melanoma Active Immunotherapy Trial) reported that patients with resected metastatic, stage III or stage IV melanoma gained no overall benefit from a combination of BCG (bacille Calmette-Guérin) and allogeneic melanoma vaccine (Canvaxin).

Similarly, at ASCO 2008, investigators in the phase III EORTC (European Organisation for Research and Treatment of Cancer) 18961 trial reported that an adjuvant vaccine that was targeted against a ganglioside that was overexpressed on most melanoma cells did not improve distant metastasis-free survival, and that an early interim analysis suggested a detriment to overall survival. (Subsequent analyses have suggested that earlier fears of harm from the vaccine may have been unwarranted, however.)

Antibodies Not Up to the Task

The goal of current therapeutic vaccines is to generate a cytotoxic T-cell response, primarily with CD8-positive effector T cells, something that has not been achieved with conventional vaccines that are primarily designed to induce antibodies.

"In most solid tumors, those antibodies are not going to be enough; they probably won’t hurt, but they’re not sufficient, and you need the T-cell response to get real tumor-cell killing," said Dr. Gajewski, a professor of pathology and medicine in the section of hematology/oncology at the University of Chicago.

GVAX in its earlier incarnation fell short of the mark because – unlike sipuleucel-T, which is an autologous vaccine comprising transduced prostatic acid phosphotase cells unique to each patient – GVAX was not specific to the tumor characteristics of individual patients, Dr. Gajewski noted.

"GVAX was an allogeneic vaccine transduced to express granulocyte-macrophage colony stimulating factor [GM-CSF], and that way you only have to express the molecule in one cell line, and then you try to administer it to all the patients hoping that there’s enough in common that they induce the immune response that recognizes the tumor in that patient. That’s true in some cases; in other cases, it’s not," he added.

"The main lesson learned in the prostate cancer trials is that the stage of cancer is critical to the success of a cancer vaccine," said BioSante president and chief executive officer Stephen Simes in an e-mail interview. "Those men who had a predicted survival (Halabi score) of 18 months or more received a benefit from the cancer vaccine, but those with a predicted survival [of less than] 18 months did not. Overall, the mean predicted survival of the men in the prostate studies was 13-16 months, hence the less-than-positive outcome. ... The men in the Provenge trials had a predicted survival of 21 months before therapy, and hence the better outcomes."

The company is finalizing a regulatory submission to remove a clinical hold on the prostate cancer vaccine, and it plans to start an open-label, phase II trial of a neoadjuvant vaccine combined with an immune checkpoint regulatory molecule. The trial will enroll patients who have a lower disease burden than do those in the previous prostate cancer vaccine trials, according to Mr. Simes.

The failed European antimelanoma vaccine trial tested the hypothesis that raising antibodies to a cell-surface component (ganglioside) could result in an antitumor effect, but "we have no good data in melanoma that antibodies against surface markers are good for very much. That’s not the mechanism the host response uses to kill tumors when it is successful," Dr. Gajewski said.

Therapeutic vaccine developers are also challenged by the considerable defenses thrown up by tumors themselves, noted Dr. Mario Sznol, vice-chief of medical oncology and codirector of the melanoma program at Yale Cancer Center in New Haven, Conn.

"None of us would expect that vaccines in general would have a very strong effect, because we already know that there are a lot of regulatory checkpoints in T-cell activation that occur beyond the initial immunization, and we know that there are a lot of things that go on in the tumor microenvironment that prevent those T cells from working well there. So while a vaccine might have some activity and be a necessary or adjunctive component to another kind of immune therapy, vaccines by themselves probably would have limited effect," he said.

Dr. Sznol, who investigates methods for overcoming tumor resistance to immune mechanisms, said that vaccines are instead likely to play an adjunctive role in combination with other, more potent immunotherapies, such as ipilimumab or cytokines such as interleukin-2.

"Vaccines might direct the immune system better or contribute to the effect, but looking at it the other way – as the vaccine being the principal component of that immunotherapy – is, I think, the wrong way to look at it," he concluded.

New Platforms, Targets, Challenges

Dr. Gajewski said that the vaccines most likely to succeed are those developed through a stepwise scientific approach, which involves methodical selection of antigens in combination with the adjuvants that produce the optimal cytotoxic T-cell response.

Therapeutic vaccines currently in development use antigens that are derived from proteins, carbohydrates, glycoproteins, glycopeptides, or gangliosides, as well as attenuated tumor-associated antigens that are employed in autologous or allogeneic formulations.

Other strategies include DNA or RNA sequences that code for cancer-associated antigens either delivered singly (naked nucleic acid vaccines) or transfected into viral vectors. Some research teams are focusing on the development of vaccines that are targeted against antigens in specific tumor types, whereas others aim for targets that are common to several different cancer histologies. The latter antigens include MAGE-3 (melanoma-encoding antigen); NY-ESO-1, found in both melanoma and synovial cell sarcoma; and WT-1, the Wilms tumor antigen that is widely expressed in leukemia.

But getting the best cytotoxic T-cell response and incorporating it into off-the-shelf vaccines are only half the battle, Dr. Gajewski said.

"The other half of the equation is whether the tumor and the tumor microenvironment are susceptible to killing by immune cells. Tumor resistance – to the activated immune cells, to cytotoxic T cells, to the effector phase of antitumor immune response – is dominant in many cases" he noted.

Many vaccine researchers are working to develop end runs around the tumor inhibitory pathways that either inactivate T cells when they infiltrate or keep them out of the tumor altogether.

"We have been able to catalog patterns of gene-expression profiling in tumors that correlate positively or negatively with outcomes, and that has identified a set of [biological] processes that seem to represent the barriers [to immunity] at the level of tumor site. And now [that we understand] those, it’s enabling ways to intervene and change the susceptibility of the tumor site to the immune response that’s induced," Dr. Gajewski said.

Dr. Gajewski has received research support for clinical trial participation from Bristol-Myers Squibb, GlaxoSmithKline-Bio, Incyte, Novartis, Eisai, and Genentech/Roche. He has served on advisory boards or served as a paid adviser to Bristol-Myers Squibb, GlaxoSmithKline-Bio, Incyte, Eisai, and Genentech/Roche. Dr. Sznol has received honoraria or served as a consultant to Bristol-Myers Squibb, Genzyme, and Pfizer.

ORLANDO – Patients with CD20-positive B-lineage acute lymphoblastic leukemia who received rituximab plus intensive chemotherapy had more durable remissions and better overall survival than did similar patients who received only chemotherapy, investigators reported at the annual meeting of the American Society of Hematology.

[Check out our comprehensive coverage of the American Society of Hematology's annual meeting.]

In standard-risk patients, the addition of rituximab improved the continuous 5-year remission rate to 76%, compared with 42% for no rituximab. In addition, 90% of those who received rituximab had a molecular complete remission (MCR) after induction, vs. 59% of those who did not receive it, said Dr. Dieter Hoelzer of Johann Wolfgang Goethe University Hospitals in Frankfurt, Germany.

Among high-risk patients younger than 55 years, rituximab improved the survival rate after stem cell transplant from 41% to 69%, said Dr. Hoelzer, chair of the German Multicenter Trial for Treatment of Newly Diagnosed Acute Lymphoblastic Leukemia in Adults (GMALL 07/2003).

The addition of rituximab was generally safe, and there were fewer treatment-related deaths in the larger cohort of patients who received rituximab. "In the rituximab arm, there is no increase of infections, but you need rigorous supportive therapy in those patients if you give rituximab and intensive chemo," Dr. Hoelzer commented.

The GMALL 07/2003 trial studied a highly complex intensive chemotherapy regimen involving cyclophosphamide, dexamethasone, vincristine, daunorubicin, doxorubicin, asparaginase, methotrexate, cytarabine, mercaptopurine, vindesine, etoposide, prednisolone, thioguanine, and teniposide, plus CNS and mediastinal irradiation. High-risk patients – those with white blood cell counts greater than 30,000/mcL and/or complete remission occurring later than 4 weeks – were offered stem cell transplantation with idarubicin, fludarabine, and cladribine with granulocyte colony–stimulating factor support.

Based on positive results with combined intensive chemotherapy and rituximab in the treatment of B-cell non-Hodgkin’s lymphoma, the protocol was amended in early 2004 to include rituximab for patients with CD20+ B-lineage acute lymphoblastic leukemia (ALL) (49% of the original GMALL 07/2003 cohort). The current study compared 82 CD20+ patients treated before the protocol was amended, and 181 treated afterward. Rituximab 375 mg/m2 was given on the day before the start of each induction, reinduction, and consolidation cycle, for a total of eight cycles.

In each cohort, more than 90% of patients had complete remissions after induction: 91% in the no-rituximab group and 94% in the rituximab arm. Among standard-risk patients younger than 55 years, 74% of those who received rituximab were still alive at longest follow-up of 6.5 years, compared with 58% of controls (no rituximab).

Rituximab was associated with a more rapid time to complete remission, with 57% of standard-risk patients who received it having an MCR by day 24, compared with 27% of controls. By week 16, 90% of patients on rituximab had an MCR, vs. 59% of controls.

Among 67 high-risk patients (43 in the rituximab arm and 24 in the no-rituximab arm), 81% of those on the CD20 inhibitor had a complete remission, compared with 88% of controls. Three patients on rituximab (7%) died during induction, compared with 1 (4%) of the controls. Stem cell transplant was possible in 25 patients on rituximab (71%) and in 19 controls (90%).

Among all high-risk patients, with or without transplant, rituximab was associated with a 55% 5-year survival rate, vs. 36% for controls, and among those who underwent transplant 5-year survival rates were 69% and 41%, respectively.

Grade 3 or 4 toxicities were generally similar in the two groups, with neutropenia occurring in 89% of patients in the rituximab arm after two induction courses, and 80% in the control arm. Fever occurred in 6% and 7%, and infection in 28% and 25%, respectively. There were three treatment-related deaths after stem cell transplant among patients on rituximab vs. four among controls.

The investigators plan to study rituximab maintenance in standard-risk patients, and whether additional rituximab given before and/or after stem cell transplant might provide additional benefits. In addition, they may examine whether rituximab has value in very-high-risk patients with B-lineage CD20+ ALL positive for the BCR-ABL fusion protein, Dr. Hoelzer said.

Dr. Hoelzer and his colleagues did not disclose the statistical significance of their findings, either in the published abstract or during the oral data presentation.

The study is sponsored by Johann Wolfgang Goethe University Hospitals in collaboration with Deutsche Krebshilfe e.V. and the German Federal Ministry of Education and Research, with partial funding from Hoffmann-La Roche. The authors had no conflict of interest disclosures. The study describes off-label use of rituximab.

ORLANDO – Patients with CD20-positive B-lineage acute lymphoblastic leukemia who received rituximab plus intensive chemotherapy had more durable remissions and better overall survival than did similar patients who received only chemotherapy, investigators reported at the annual meeting of the American Society of Hematology.

[Check out our comprehensive coverage of the American Society of Hematology's annual meeting.]

In standard-risk patients, the addition of rituximab improved the continuous 5-year remission rate to 76%, compared with 42% for no rituximab. In addition, 90% of those who received rituximab had a molecular complete remission (MCR) after induction, vs. 59% of those who did not receive it, said Dr. Dieter Hoelzer of Johann Wolfgang Goethe University Hospitals in Frankfurt, Germany.

Among high-risk patients younger than 55 years, rituximab improved the survival rate after stem cell transplant from 41% to 69%, said Dr. Hoelzer, chair of the German Multicenter Trial for Treatment of Newly Diagnosed Acute Lymphoblastic Leukemia in Adults (GMALL 07/2003).

The addition of rituximab was generally safe, and there were fewer treatment-related deaths in the larger cohort of patients who received rituximab. "In the rituximab arm, there is no increase of infections, but you need rigorous supportive therapy in those patients if you give rituximab and intensive chemo," Dr. Hoelzer commented.

The GMALL 07/2003 trial studied a highly complex intensive chemotherapy regimen involving cyclophosphamide, dexamethasone, vincristine, daunorubicin, doxorubicin, asparaginase, methotrexate, cytarabine, mercaptopurine, vindesine, etoposide, prednisolone, thioguanine, and teniposide, plus CNS and mediastinal irradiation. High-risk patients – those with white blood cell counts greater than 30,000/mcL and/or complete remission occurring later than 4 weeks – were offered stem cell transplantation with idarubicin, fludarabine, and cladribine with granulocyte colony–stimulating factor support.

Based on positive results with combined intensive chemotherapy and rituximab in the treatment of B-cell non-Hodgkin’s lymphoma, the protocol was amended in early 2004 to include rituximab for patients with CD20+ B-lineage acute lymphoblastic leukemia (ALL) (49% of the original GMALL 07/2003 cohort). The current study compared 82 CD20+ patients treated before the protocol was amended, and 181 treated afterward. Rituximab 375 mg/m2 was given on the day before the start of each induction, reinduction, and consolidation cycle, for a total of eight cycles.

In each cohort, more than 90% of patients had complete remissions after induction: 91% in the no-rituximab group and 94% in the rituximab arm. Among standard-risk patients younger than 55 years, 74% of those who received rituximab were still alive at longest follow-up of 6.5 years, compared with 58% of controls (no rituximab).

Rituximab was associated with a more rapid time to complete remission, with 57% of standard-risk patients who received it having an MCR by day 24, compared with 27% of controls. By week 16, 90% of patients on rituximab had an MCR, vs. 59% of controls.

Among 67 high-risk patients (43 in the rituximab arm and 24 in the no-rituximab arm), 81% of those on the CD20 inhibitor had a complete remission, compared with 88% of controls. Three patients on rituximab (7%) died during induction, compared with 1 (4%) of the controls. Stem cell transplant was possible in 25 patients on rituximab (71%) and in 19 controls (90%).

Among all high-risk patients, with or without transplant, rituximab was associated with a 55% 5-year survival rate, vs. 36% for controls, and among those who underwent transplant 5-year survival rates were 69% and 41%, respectively.

Grade 3 or 4 toxicities were generally similar in the two groups, with neutropenia occurring in 89% of patients in the rituximab arm after two induction courses, and 80% in the control arm. Fever occurred in 6% and 7%, and infection in 28% and 25%, respectively. There were three treatment-related deaths after stem cell transplant among patients on rituximab vs. four among controls.

The investigators plan to study rituximab maintenance in standard-risk patients, and whether additional rituximab given before and/or after stem cell transplant might provide additional benefits. In addition, they may examine whether rituximab has value in very-high-risk patients with B-lineage CD20+ ALL positive for the BCR-ABL fusion protein, Dr. Hoelzer said.

Dr. Hoelzer and his colleagues did not disclose the statistical significance of their findings, either in the published abstract or during the oral data presentation.

The study is sponsored by Johann Wolfgang Goethe University Hospitals in collaboration with Deutsche Krebshilfe e.V. and the German Federal Ministry of Education and Research, with partial funding from Hoffmann-La Roche. The authors had no conflict of interest disclosures. The study describes off-label use of rituximab.

ORLANDO – Patients with CD20-positive B-lineage acute lymphoblastic leukemia who received rituximab plus intensive chemotherapy had more durable remissions and better overall survival than did similar patients who received only chemotherapy, investigators reported at the annual meeting of the American Society of Hematology.

[Check out our comprehensive coverage of the American Society of Hematology's annual meeting.]

In standard-risk patients, the addition of rituximab improved the continuous 5-year remission rate to 76%, compared with 42% for no rituximab. In addition, 90% of those who received rituximab had a molecular complete remission (MCR) after induction, vs. 59% of those who did not receive it, said Dr. Dieter Hoelzer of Johann Wolfgang Goethe University Hospitals in Frankfurt, Germany.

Among high-risk patients younger than 55 years, rituximab improved the survival rate after stem cell transplant from 41% to 69%, said Dr. Hoelzer, chair of the German Multicenter Trial for Treatment of Newly Diagnosed Acute Lymphoblastic Leukemia in Adults (GMALL 07/2003).

The addition of rituximab was generally safe, and there were fewer treatment-related deaths in the larger cohort of patients who received rituximab. "In the rituximab arm, there is no increase of infections, but you need rigorous supportive therapy in those patients if you give rituximab and intensive chemo," Dr. Hoelzer commented.

The GMALL 07/2003 trial studied a highly complex intensive chemotherapy regimen involving cyclophosphamide, dexamethasone, vincristine, daunorubicin, doxorubicin, asparaginase, methotrexate, cytarabine, mercaptopurine, vindesine, etoposide, prednisolone, thioguanine, and teniposide, plus CNS and mediastinal irradiation. High-risk patients – those with white blood cell counts greater than 30,000/mcL and/or complete remission occurring later than 4 weeks – were offered stem cell transplantation with idarubicin, fludarabine, and cladribine with granulocyte colony–stimulating factor support.

Based on positive results with combined intensive chemotherapy and rituximab in the treatment of B-cell non-Hodgkin’s lymphoma, the protocol was amended in early 2004 to include rituximab for patients with CD20+ B-lineage acute lymphoblastic leukemia (ALL) (49% of the original GMALL 07/2003 cohort). The current study compared 82 CD20+ patients treated before the protocol was amended, and 181 treated afterward. Rituximab 375 mg/m2 was given on the day before the start of each induction, reinduction, and consolidation cycle, for a total of eight cycles.

In each cohort, more than 90% of patients had complete remissions after induction: 91% in the no-rituximab group and 94% in the rituximab arm. Among standard-risk patients younger than 55 years, 74% of those who received rituximab were still alive at longest follow-up of 6.5 years, compared with 58% of controls (no rituximab).

Rituximab was associated with a more rapid time to complete remission, with 57% of standard-risk patients who received it having an MCR by day 24, compared with 27% of controls. By week 16, 90% of patients on rituximab had an MCR, vs. 59% of controls.

Among 67 high-risk patients (43 in the rituximab arm and 24 in the no-rituximab arm), 81% of those on the CD20 inhibitor had a complete remission, compared with 88% of controls. Three patients on rituximab (7%) died during induction, compared with 1 (4%) of the controls. Stem cell transplant was possible in 25 patients on rituximab (71%) and in 19 controls (90%).

Among all high-risk patients, with or without transplant, rituximab was associated with a 55% 5-year survival rate, vs. 36% for controls, and among those who underwent transplant 5-year survival rates were 69% and 41%, respectively.

Grade 3 or 4 toxicities were generally similar in the two groups, with neutropenia occurring in 89% of patients in the rituximab arm after two induction courses, and 80% in the control arm. Fever occurred in 6% and 7%, and infection in 28% and 25%, respectively. There were three treatment-related deaths after stem cell transplant among patients on rituximab vs. four among controls.

The investigators plan to study rituximab maintenance in standard-risk patients, and whether additional rituximab given before and/or after stem cell transplant might provide additional benefits. In addition, they may examine whether rituximab has value in very-high-risk patients with B-lineage CD20+ ALL positive for the BCR-ABL fusion protein, Dr. Hoelzer said.

Dr. Hoelzer and his colleagues did not disclose the statistical significance of their findings, either in the published abstract or during the oral data presentation.

The study is sponsored by Johann Wolfgang Goethe University Hospitals in collaboration with Deutsche Krebshilfe e.V. and the German Federal Ministry of Education and Research, with partial funding from Hoffmann-La Roche. The authors had no conflict of interest disclosures. The study describes off-label use of rituximab.

ORLANDO – Donors of bone marrow or peripheral blood stem cells can rest assured that their generous acts are unlikely to have any lingering negative consequences to their own health, investigators reported at the annual meeting of the American Society of Hematology.

A survey collecting 55,228 observation-years of health data on 12,559 donors of bone-marrow and/or peripheral blood stem cells (PBSC) to unrelated recipients suggests that despite receiving granulocyte–colony-stimulating factor (G-CSF), donors are not at increased risk for hematologic malignancies or other significant health problems down the road, said Dr. Alexander H. Schmidt of the DKMS German Bone Marrow Donor Center in T?bingen, Germany.

Looking at standard incidence ratios (SIR) for leukemias, lymphomas, plasmocytoma, and lung cancer, the authors found no evidence of increased risk associated with donation.

Although bone marrow donors (but not PBSC donors) had a threefold higher incidence of malignant melanoma compared with the general German population, this finding was likely a statistical artifact, "because there is no mechanism available that would explain how bone marrow donation could increase the risk of development of malignant melanoma," Dr. Schmidt said at a media briefing where DKMS was described as the largest bone marrow donation center in the world.

In addition, the incidence of lung cancer was lower than expected among donors, who may be more focused on health concerns than nondonors and thus less likely to smoke.

"We found no evidence that bone marrow or PBSC donation might be unsafe procedures, so there’s no need to change policies from our point of view," he said.

[Treatment-Related Death Toll Casts Doubt on "Auto-Allo" Transplants in Myeloma]

A handful of studies has suggested that hematopoietic agents such as G-CSF may increase risk for hematologic malignancies among healthy donors who receive them, Dr. Schmidt said.

For example, Dr. Charles L. Bennett and colleagues at the Northwestern University Feinberg School of Medicine in Chicago reviewed findings on donors who developed hematologic malignancies 1-5 years after receiving hematopoietic agents. The authors found that "while a causal relationship with hematological malignancies cannot be demonstrated, long-term follow-up among healthy individuals who receive hematopoietic growth factors is needed." (Br. J. Haematol. 2006;135:642-50).

But to tease out potentially harmful effects with any degree of certainty requires a large sample of donors who are willing to participate in a survey, Dr. Schmidt said. To capture as many donors as possible, he and his colleagues devised a simple survey asking donors about their general health, hospitalizations or long-term medical therapy (and the underlying disease) since donation, prescription drugs they took regularly or for a minimum of 4 weeks since donating, and whether they were willing to donate again.

They received replies from 81.3% of the 15,456 donors to whom they mailed the questionnaires, for a total of 12,559 completed and returned responses. That translated into 30,777 observation-years for 8,730 PBSC donors, 23,037 observation-years for 3,556 bone marrow donors, and 1,414 observation-years for 273 donors of both marrow and PBSC. Median follow-up time since donation was 3.3 years.

Overall, 95.1% of PBSC donors rated their health as very good or good, as did 96.0% of marrow donors, and 92.2% of those who gave both PBSC and marrow (comparison of PBSC and marrow donors, chi-squared test, P = .03)

PBSC donors had significantly fewer hospitalizations or new prescriptions than did bone marrow donors in a univariate analysis (chi-square tests, P less than .001), but this difference did not hold up in multivariate analysis. Because there were significantly more men and younger PBSC donors than bone marrow donors, the differences detected in health-related problems between the donor groups in the univariate analysis may be attributable to differences in sample characteristics, the investigators said.

A total of 85 malignancies were reported: 50 among 48 stem-cell donors, 31 in marrow donors, and 4 in donors of both. Six of these malignancies were hematologic: two cases of Hodgkin’s disease, both occurring in PBSC donors; one plasmocytoma in a PBSC donor; one acute myeloid leukemia in a bone marrow donor; one non-Hodgkin’s lymphoma in a bone marrow donor; and one chronic myeloid leukemia in a dual donor. (In addition, the investigators said they learned of 21 more donor malignancies in reports from donor centers; 5 of these were hematologic.)

The SIR for all malignancies among all donors was 0.99. There were no significant differences in the incidences of leukemia, non-Hodgkin lymphoma, plasmocytoma, or Hodgkin’s disease from those of age- and gender-adjusted incidences in the German population.

Dr. Schmidt said that the data exclude the possibility of a threefold or greater risk for leukemia in PBSC donors.

The authors said they had no relevant conflicts of interest.

ORLANDO – Donors of bone marrow or peripheral blood stem cells can rest assured that their generous acts are unlikely to have any lingering negative consequences to their own health, investigators reported at the annual meeting of the American Society of Hematology.

A survey collecting 55,228 observation-years of health data on 12,559 donors of bone-marrow and/or peripheral blood stem cells (PBSC) to unrelated recipients suggests that despite receiving granulocyte–colony-stimulating factor (G-CSF), donors are not at increased risk for hematologic malignancies or other significant health problems down the road, said Dr. Alexander H. Schmidt of the DKMS German Bone Marrow Donor Center in T?bingen, Germany.

Looking at standard incidence ratios (SIR) for leukemias, lymphomas, plasmocytoma, and lung cancer, the authors found no evidence of increased risk associated with donation.

Although bone marrow donors (but not PBSC donors) had a threefold higher incidence of malignant melanoma compared with the general German population, this finding was likely a statistical artifact, "because there is no mechanism available that would explain how bone marrow donation could increase the risk of development of malignant melanoma," Dr. Schmidt said at a media briefing where DKMS was described as the largest bone marrow donation center in the world.

In addition, the incidence of lung cancer was lower than expected among donors, who may be more focused on health concerns than nondonors and thus less likely to smoke.

"We found no evidence that bone marrow or PBSC donation might be unsafe procedures, so there’s no need to change policies from our point of view," he said.

[Treatment-Related Death Toll Casts Doubt on "Auto-Allo" Transplants in Myeloma]

A handful of studies has suggested that hematopoietic agents such as G-CSF may increase risk for hematologic malignancies among healthy donors who receive them, Dr. Schmidt said.

For example, Dr. Charles L. Bennett and colleagues at the Northwestern University Feinberg School of Medicine in Chicago reviewed findings on donors who developed hematologic malignancies 1-5 years after receiving hematopoietic agents. The authors found that "while a causal relationship with hematological malignancies cannot be demonstrated, long-term follow-up among healthy individuals who receive hematopoietic growth factors is needed." (Br. J. Haematol. 2006;135:642-50).

But to tease out potentially harmful effects with any degree of certainty requires a large sample of donors who are willing to participate in a survey, Dr. Schmidt said. To capture as many donors as possible, he and his colleagues devised a simple survey asking donors about their general health, hospitalizations or long-term medical therapy (and the underlying disease) since donation, prescription drugs they took regularly or for a minimum of 4 weeks since donating, and whether they were willing to donate again.

They received replies from 81.3% of the 15,456 donors to whom they mailed the questionnaires, for a total of 12,559 completed and returned responses. That translated into 30,777 observation-years for 8,730 PBSC donors, 23,037 observation-years for 3,556 bone marrow donors, and 1,414 observation-years for 273 donors of both marrow and PBSC. Median follow-up time since donation was 3.3 years.

Overall, 95.1% of PBSC donors rated their health as very good or good, as did 96.0% of marrow donors, and 92.2% of those who gave both PBSC and marrow (comparison of PBSC and marrow donors, chi-squared test, P = .03)

PBSC donors had significantly fewer hospitalizations or new prescriptions than did bone marrow donors in a univariate analysis (chi-square tests, P less than .001), but this difference did not hold up in multivariate analysis. Because there were significantly more men and younger PBSC donors than bone marrow donors, the differences detected in health-related problems between the donor groups in the univariate analysis may be attributable to differences in sample characteristics, the investigators said.

A total of 85 malignancies were reported: 50 among 48 stem-cell donors, 31 in marrow donors, and 4 in donors of both. Six of these malignancies were hematologic: two cases of Hodgkin’s disease, both occurring in PBSC donors; one plasmocytoma in a PBSC donor; one acute myeloid leukemia in a bone marrow donor; one non-Hodgkin’s lymphoma in a bone marrow donor; and one chronic myeloid leukemia in a dual donor. (In addition, the investigators said they learned of 21 more donor malignancies in reports from donor centers; 5 of these were hematologic.)

The SIR for all malignancies among all donors was 0.99. There were no significant differences in the incidences of leukemia, non-Hodgkin lymphoma, plasmocytoma, or Hodgkin’s disease from those of age- and gender-adjusted incidences in the German population.

Dr. Schmidt said that the data exclude the possibility of a threefold or greater risk for leukemia in PBSC donors.

The authors said they had no relevant conflicts of interest.

ORLANDO – Donors of bone marrow or peripheral blood stem cells can rest assured that their generous acts are unlikely to have any lingering negative consequences to their own health, investigators reported at the annual meeting of the American Society of Hematology.

A survey collecting 55,228 observation-years of health data on 12,559 donors of bone-marrow and/or peripheral blood stem cells (PBSC) to unrelated recipients suggests that despite receiving granulocyte–colony-stimulating factor (G-CSF), donors are not at increased risk for hematologic malignancies or other significant health problems down the road, said Dr. Alexander H. Schmidt of the DKMS German Bone Marrow Donor Center in T?bingen, Germany.

Looking at standard incidence ratios (SIR) for leukemias, lymphomas, plasmocytoma, and lung cancer, the authors found no evidence of increased risk associated with donation.

Although bone marrow donors (but not PBSC donors) had a threefold higher incidence of malignant melanoma compared with the general German population, this finding was likely a statistical artifact, "because there is no mechanism available that would explain how bone marrow donation could increase the risk of development of malignant melanoma," Dr. Schmidt said at a media briefing where DKMS was described as the largest bone marrow donation center in the world.

In addition, the incidence of lung cancer was lower than expected among donors, who may be more focused on health concerns than nondonors and thus less likely to smoke.

"We found no evidence that bone marrow or PBSC donation might be unsafe procedures, so there’s no need to change policies from our point of view," he said.

[Treatment-Related Death Toll Casts Doubt on "Auto-Allo" Transplants in Myeloma]

A handful of studies has suggested that hematopoietic agents such as G-CSF may increase risk for hematologic malignancies among healthy donors who receive them, Dr. Schmidt said.

For example, Dr. Charles L. Bennett and colleagues at the Northwestern University Feinberg School of Medicine in Chicago reviewed findings on donors who developed hematologic malignancies 1-5 years after receiving hematopoietic agents. The authors found that "while a causal relationship with hematological malignancies cannot be demonstrated, long-term follow-up among healthy individuals who receive hematopoietic growth factors is needed." (Br. J. Haematol. 2006;135:642-50).

But to tease out potentially harmful effects with any degree of certainty requires a large sample of donors who are willing to participate in a survey, Dr. Schmidt said. To capture as many donors as possible, he and his colleagues devised a simple survey asking donors about their general health, hospitalizations or long-term medical therapy (and the underlying disease) since donation, prescription drugs they took regularly or for a minimum of 4 weeks since donating, and whether they were willing to donate again.

They received replies from 81.3% of the 15,456 donors to whom they mailed the questionnaires, for a total of 12,559 completed and returned responses. That translated into 30,777 observation-years for 8,730 PBSC donors, 23,037 observation-years for 3,556 bone marrow donors, and 1,414 observation-years for 273 donors of both marrow and PBSC. Median follow-up time since donation was 3.3 years.

Overall, 95.1% of PBSC donors rated their health as very good or good, as did 96.0% of marrow donors, and 92.2% of those who gave both PBSC and marrow (comparison of PBSC and marrow donors, chi-squared test, P = .03)

PBSC donors had significantly fewer hospitalizations or new prescriptions than did bone marrow donors in a univariate analysis (chi-square tests, P less than .001), but this difference did not hold up in multivariate analysis. Because there were significantly more men and younger PBSC donors than bone marrow donors, the differences detected in health-related problems between the donor groups in the univariate analysis may be attributable to differences in sample characteristics, the investigators said.

A total of 85 malignancies were reported: 50 among 48 stem-cell donors, 31 in marrow donors, and 4 in donors of both. Six of these malignancies were hematologic: two cases of Hodgkin’s disease, both occurring in PBSC donors; one plasmocytoma in a PBSC donor; one acute myeloid leukemia in a bone marrow donor; one non-Hodgkin’s lymphoma in a bone marrow donor; and one chronic myeloid leukemia in a dual donor. (In addition, the investigators said they learned of 21 more donor malignancies in reports from donor centers; 5 of these were hematologic.)

The SIR for all malignancies among all donors was 0.99. There were no significant differences in the incidences of leukemia, non-Hodgkin lymphoma, plasmocytoma, or Hodgkin’s disease from those of age- and gender-adjusted incidences in the German population.

Dr. Schmidt said that the data exclude the possibility of a threefold or greater risk for leukemia in PBSC donors.

The authors said they had no relevant conflicts of interest.

ORLANDO – A novel liposomal combination of cytarabine plus daunorubicin produced higher complete remission rates than did the standard "7+3" cytarabine-daunorubicin induction regimen in older patients with untreated acute myeloid leukemia, reported investigators at the annual meeting of the American Society of Hematology.

In a phase IIB randomized trial, 66.7% of patients with newly diagnosed AML who underwent induction with the liposomal formulation, dubbed CPX-351, had complete remissions (CR) or complete remissions with incomplete peripheral blood count recovery (CRi), compared with 51.2% of patients who received induction with the 7+3 regimen, a difference that fell a bit shy of statistical significance (P = .0712), reported Dr. Jeffrey E. Lancet from the H. Lee Moffitt Cancer Center in Tampa.

CPX-351 was associated with significantly better overall survival in the subgroup of patients with secondary AML (median, 12.1 months vs. 6.1 months; log rank P = .01). The liposomal compound also appeared to have an edge in high cytogenetic risk patients, with 17 of 23 patients (73.9%) who received it having a remission, compared with 5 of 13 (38.5%) who were given the standard therapy, but this difference too fell just outside the boundary of significance (P = .07), said Dr. Lancet.

"In terms of future directions, we feel that there is a strong signal of activity with the drug, and phase III trials are being planned for sometime next year," he said. "There are still some options on the table to consider, including isolating the patient population to a secondary AML subgroup, to look at a more generalized group of high-risk AML patients, or perhaps to look at a more unselected group of patients, but I think that additional follow-up data and analysis will be necessary before making this decision."

CPX-351 is a liposome that delivers cytarabine and daunorubicin in a 5:1 molar ratio for more than 24 hours after infusion. The agent accumulates and persists in the bone marrow, and has been shown to have preferential uptake and intracellular release within leukemic blasts, compared with nonleukemic progenitor cells.

In phase I trials, CPX-351 was associated with clinical responses in patients with advanced AML, including some for whom 7+3 therapy had failed. Dose-limiting toxicities were hypertensive crisis, cardiomyopathies, and one case of prolonged cytopenia.

In the phase IIB trial, patients aged 60-75 years with newly diagnosed AML were randomly assigned in a 2:1 ratio to receive CPX-351 in doses of 100 U/m2 on days 1, 3 and 5, or 7+3 therapy with cytarabine 100 mg/m2 in a 7-day continuous infusion plus daunorubicin 60 mg/m2 on days 1, 2, and 3 – each regimen for one or two induction cycles. Patients who experienced CR or CRi then went on to one or two consolidation cycles. The trial included an optional crossover arm for patients in the 7+3 arm who had persistent AML following induction. The primary end point was the combined CR-plus-CRi rate.

In all, 126 patients from 18 sites in the United States and Canada were enrolled, 85 in the CPX-351 arm, and 41 in 7+3 arm. One patient who was initially enrolled in the CPX-351 arm was found to have Philadelphia chromosome–positive AML and was removed from the study for treatment with imatinib (Gleevec), leaving 84 patients on CPX-351 for the efficacy and safety analysis.

Following induction, 41 patients on CPX-351 (48.8%) had a CR, and 15 (17.9%) had a CRi, compared with 20 (48.8%) and 1 (2.4%) patients on the 7+3 regimen. An analysis of efficacy by subgroups showed that CPX-351 induced higher remission rates in patients younger than 70 years and those aged 70 and older, and in patients with secondary AML, compared with de novo disease, although the sample sizes for these comparisons were not sufficiently large to determine significance.

Early deaths from all causes were similarly lower in the CPX group at 30 days (3.5% vs. 7.3% for the 7+3 group) and at 60 days (4.7% vs. 14.6%; P = .053). All early deaths occurred in high-risk patients.

In the overall efficacy analysis, there were no significant differences between CPX-351 and 7+3 in either event-free survival (remission duration, 8.9 and 8.6 months, respectively) or overall survival (median, 14.7 and 12.9 months).

The optional crossover arm included 10 patients, 1 of whom switched after two induction cycles and 9 after one cycle. Of these patients, four had responses, and all four were alive at the 1-year follow-up.

The safety analysis showed that CPX-351 was associated with a higher percentage of grade 3 or 4 febrile neutropenia (63.5% vs. 51.2%) and clinical infections (70.6% vs. 46.3%), as well as with longer myelosuppression, including about 7 days longer neutrophil recovery, and about 10 days longer platelet recovery than was the case for patients receiving the standard chemotherapy. The higher incidence of infections with the experimental agent did not appear to result in worse outcomes, however, as the overall rate of deaths attributable to infections was low in each arm, Dr. Lancet said.

CPX-351 has orphan drug status for the treatment of AML, according to the Celator Web site.

Celator Pharmaceuticals sponsored the trial. Dr. Lancet disclosed that his center received compensation from the company, and he has served on the board of directors or advisory committees. Two coauthors also disclosed serving on the board or as advisors, and one is employed by the company.

ORLANDO – A novel liposomal combination of cytarabine plus daunorubicin produced higher complete remission rates than did the standard "7+3" cytarabine-daunorubicin induction regimen in older patients with untreated acute myeloid leukemia, reported investigators at the annual meeting of the American Society of Hematology.

In a phase IIB randomized trial, 66.7% of patients with newly diagnosed AML who underwent induction with the liposomal formulation, dubbed CPX-351, had complete remissions (CR) or complete remissions with incomplete peripheral blood count recovery (CRi), compared with 51.2% of patients who received induction with the 7+3 regimen, a difference that fell a bit shy of statistical significance (P = .0712), reported Dr. Jeffrey E. Lancet from the H. Lee Moffitt Cancer Center in Tampa.

CPX-351 was associated with significantly better overall survival in the subgroup of patients with secondary AML (median, 12.1 months vs. 6.1 months; log rank P = .01). The liposomal compound also appeared to have an edge in high cytogenetic risk patients, with 17 of 23 patients (73.9%) who received it having a remission, compared with 5 of 13 (38.5%) who were given the standard therapy, but this difference too fell just outside the boundary of significance (P = .07), said Dr. Lancet.

"In terms of future directions, we feel that there is a strong signal of activity with the drug, and phase III trials are being planned for sometime next year," he said. "There are still some options on the table to consider, including isolating the patient population to a secondary AML subgroup, to look at a more generalized group of high-risk AML patients, or perhaps to look at a more unselected group of patients, but I think that additional follow-up data and analysis will be necessary before making this decision."

CPX-351 is a liposome that delivers cytarabine and daunorubicin in a 5:1 molar ratio for more than 24 hours after infusion. The agent accumulates and persists in the bone marrow, and has been shown to have preferential uptake and intracellular release within leukemic blasts, compared with nonleukemic progenitor cells.

In phase I trials, CPX-351 was associated with clinical responses in patients with advanced AML, including some for whom 7+3 therapy had failed. Dose-limiting toxicities were hypertensive crisis, cardiomyopathies, and one case of prolonged cytopenia.

In the phase IIB trial, patients aged 60-75 years with newly diagnosed AML were randomly assigned in a 2:1 ratio to receive CPX-351 in doses of 100 U/m2 on days 1, 3 and 5, or 7+3 therapy with cytarabine 100 mg/m2 in a 7-day continuous infusion plus daunorubicin 60 mg/m2 on days 1, 2, and 3 – each regimen for one or two induction cycles. Patients who experienced CR or CRi then went on to one or two consolidation cycles. The trial included an optional crossover arm for patients in the 7+3 arm who had persistent AML following induction. The primary end point was the combined CR-plus-CRi rate.

In all, 126 patients from 18 sites in the United States and Canada were enrolled, 85 in the CPX-351 arm, and 41 in 7+3 arm. One patient who was initially enrolled in the CPX-351 arm was found to have Philadelphia chromosome–positive AML and was removed from the study for treatment with imatinib (Gleevec), leaving 84 patients on CPX-351 for the efficacy and safety analysis.

Following induction, 41 patients on CPX-351 (48.8%) had a CR, and 15 (17.9%) had a CRi, compared with 20 (48.8%) and 1 (2.4%) patients on the 7+3 regimen. An analysis of efficacy by subgroups showed that CPX-351 induced higher remission rates in patients younger than 70 years and those aged 70 and older, and in patients with secondary AML, compared with de novo disease, although the sample sizes for these comparisons were not sufficiently large to determine significance.

Early deaths from all causes were similarly lower in the CPX group at 30 days (3.5% vs. 7.3% for the 7+3 group) and at 60 days (4.7% vs. 14.6%; P = .053). All early deaths occurred in high-risk patients.

In the overall efficacy analysis, there were no significant differences between CPX-351 and 7+3 in either event-free survival (remission duration, 8.9 and 8.6 months, respectively) or overall survival (median, 14.7 and 12.9 months).

The optional crossover arm included 10 patients, 1 of whom switched after two induction cycles and 9 after one cycle. Of these patients, four had responses, and all four were alive at the 1-year follow-up.

The safety analysis showed that CPX-351 was associated with a higher percentage of grade 3 or 4 febrile neutropenia (63.5% vs. 51.2%) and clinical infections (70.6% vs. 46.3%), as well as with longer myelosuppression, including about 7 days longer neutrophil recovery, and about 10 days longer platelet recovery than was the case for patients receiving the standard chemotherapy. The higher incidence of infections with the experimental agent did not appear to result in worse outcomes, however, as the overall rate of deaths attributable to infections was low in each arm, Dr. Lancet said.

CPX-351 has orphan drug status for the treatment of AML, according to the Celator Web site.

Celator Pharmaceuticals sponsored the trial. Dr. Lancet disclosed that his center received compensation from the company, and he has served on the board of directors or advisory committees. Two coauthors also disclosed serving on the board or as advisors, and one is employed by the company.

ORLANDO – A novel liposomal combination of cytarabine plus daunorubicin produced higher complete remission rates than did the standard "7+3" cytarabine-daunorubicin induction regimen in older patients with untreated acute myeloid leukemia, reported investigators at the annual meeting of the American Society of Hematology.

In a phase IIB randomized trial, 66.7% of patients with newly diagnosed AML who underwent induction with the liposomal formulation, dubbed CPX-351, had complete remissions (CR) or complete remissions with incomplete peripheral blood count recovery (CRi), compared with 51.2% of patients who received induction with the 7+3 regimen, a difference that fell a bit shy of statistical significance (P = .0712), reported Dr. Jeffrey E. Lancet from the H. Lee Moffitt Cancer Center in Tampa.

CPX-351 was associated with significantly better overall survival in the subgroup of patients with secondary AML (median, 12.1 months vs. 6.1 months; log rank P = .01). The liposomal compound also appeared to have an edge in high cytogenetic risk patients, with 17 of 23 patients (73.9%) who received it having a remission, compared with 5 of 13 (38.5%) who were given the standard therapy, but this difference too fell just outside the boundary of significance (P = .07), said Dr. Lancet.

"In terms of future directions, we feel that there is a strong signal of activity with the drug, and phase III trials are being planned for sometime next year," he said. "There are still some options on the table to consider, including isolating the patient population to a secondary AML subgroup, to look at a more generalized group of high-risk AML patients, or perhaps to look at a more unselected group of patients, but I think that additional follow-up data and analysis will be necessary before making this decision."

CPX-351 is a liposome that delivers cytarabine and daunorubicin in a 5:1 molar ratio for more than 24 hours after infusion. The agent accumulates and persists in the bone marrow, and has been shown to have preferential uptake and intracellular release within leukemic blasts, compared with nonleukemic progenitor cells.

In phase I trials, CPX-351 was associated with clinical responses in patients with advanced AML, including some for whom 7+3 therapy had failed. Dose-limiting toxicities were hypertensive crisis, cardiomyopathies, and one case of prolonged cytopenia.

In the phase IIB trial, patients aged 60-75 years with newly diagnosed AML were randomly assigned in a 2:1 ratio to receive CPX-351 in doses of 100 U/m2 on days 1, 3 and 5, or 7+3 therapy with cytarabine 100 mg/m2 in a 7-day continuous infusion plus daunorubicin 60 mg/m2 on days 1, 2, and 3 – each regimen for one or two induction cycles. Patients who experienced CR or CRi then went on to one or two consolidation cycles. The trial included an optional crossover arm for patients in the 7+3 arm who had persistent AML following induction. The primary end point was the combined CR-plus-CRi rate.

In all, 126 patients from 18 sites in the United States and Canada were enrolled, 85 in the CPX-351 arm, and 41 in 7+3 arm. One patient who was initially enrolled in the CPX-351 arm was found to have Philadelphia chromosome–positive AML and was removed from the study for treatment with imatinib (Gleevec), leaving 84 patients on CPX-351 for the efficacy and safety analysis.

Following induction, 41 patients on CPX-351 (48.8%) had a CR, and 15 (17.9%) had a CRi, compared with 20 (48.8%) and 1 (2.4%) patients on the 7+3 regimen. An analysis of efficacy by subgroups showed that CPX-351 induced higher remission rates in patients younger than 70 years and those aged 70 and older, and in patients with secondary AML, compared with de novo disease, although the sample sizes for these comparisons were not sufficiently large to determine significance.

Early deaths from all causes were similarly lower in the CPX group at 30 days (3.5% vs. 7.3% for the 7+3 group) and at 60 days (4.7% vs. 14.6%; P = .053). All early deaths occurred in high-risk patients.

In the overall efficacy analysis, there were no significant differences between CPX-351 and 7+3 in either event-free survival (remission duration, 8.9 and 8.6 months, respectively) or overall survival (median, 14.7 and 12.9 months).

The optional crossover arm included 10 patients, 1 of whom switched after two induction cycles and 9 after one cycle. Of these patients, four had responses, and all four were alive at the 1-year follow-up.

The safety analysis showed that CPX-351 was associated with a higher percentage of grade 3 or 4 febrile neutropenia (63.5% vs. 51.2%) and clinical infections (70.6% vs. 46.3%), as well as with longer myelosuppression, including about 7 days longer neutrophil recovery, and about 10 days longer platelet recovery than was the case for patients receiving the standard chemotherapy. The higher incidence of infections with the experimental agent did not appear to result in worse outcomes, however, as the overall rate of deaths attributable to infections was low in each arm, Dr. Lancet said.

CPX-351 has orphan drug status for the treatment of AML, according to the Celator Web site.

Celator Pharmaceuticals sponsored the trial. Dr. Lancet disclosed that his center received compensation from the company, and he has served on the board of directors or advisory committees. Two coauthors also disclosed serving on the board or as advisors, and one is employed by the company.