Leukemia, Myelodysplasia, Transplantation

Lab rat

Photo by Janet Stevens

Human neural stem cell treatments are showing promise for reversing learning and memory deficits after chemotherapy, according to an article in Cancer Research.

Investigators found that transplanting stem cells in rats a week after they completed a series of chemotherapy sessions restored a range of cognitive functions, as

measured a month later via behavioral testing.

In contrast, animals that did not receive stem cells showed significant learning and memory impairment.

“Our findings provide the first solid evidence that transplantation of human neural stem cells can be used to reverse chemotherapeutic-induced damage of healthy tissue in the brain,” said study author Charles Limoli, PhD, of the University of California, Irvine.

For this study, Dr Limoli and his colleagues transplanted adult neural stem cells into the brains of rats that had received cyclophosphamide.

The cells migrated throughout the hippocampus, where they survived and differentiated into multiple neural cell types. Additionally, these cells triggered the secretion of neurotrophic growth factors that helped rebuild wounded neurons.

The investigators also found that engrafted cells protected the host neurons, thereby preventing the loss or promoting the repair of damaged neurons and their finer structural elements, referred to as dendritic spines.

“This research suggests that stem cell therapies may one day be implemented in the clinic to provide relief to patients suffering from cognitive impairments incurred as a result of their cancer treatments,” Dr Limoli said. “While much work remains, a clinical trial analyzing the safety of such approaches may be possible within a few years.”

Lab rat

Photo by Janet Stevens

Human neural stem cell treatments are showing promise for reversing learning and memory deficits after chemotherapy, according to an article in Cancer Research.

Investigators found that transplanting stem cells in rats a week after they completed a series of chemotherapy sessions restored a range of cognitive functions, as

measured a month later via behavioral testing.

In contrast, animals that did not receive stem cells showed significant learning and memory impairment.

“Our findings provide the first solid evidence that transplantation of human neural stem cells can be used to reverse chemotherapeutic-induced damage of healthy tissue in the brain,” said study author Charles Limoli, PhD, of the University of California, Irvine.

For this study, Dr Limoli and his colleagues transplanted adult neural stem cells into the brains of rats that had received cyclophosphamide.

The cells migrated throughout the hippocampus, where they survived and differentiated into multiple neural cell types. Additionally, these cells triggered the secretion of neurotrophic growth factors that helped rebuild wounded neurons.

The investigators also found that engrafted cells protected the host neurons, thereby preventing the loss or promoting the repair of damaged neurons and their finer structural elements, referred to as dendritic spines.

“This research suggests that stem cell therapies may one day be implemented in the clinic to provide relief to patients suffering from cognitive impairments incurred as a result of their cancer treatments,” Dr Limoli said. “While much work remains, a clinical trial analyzing the safety of such approaches may be possible within a few years.”

Lab rat

Photo by Janet Stevens

Human neural stem cell treatments are showing promise for reversing learning and memory deficits after chemotherapy, according to an article in Cancer Research.

Investigators found that transplanting stem cells in rats a week after they completed a series of chemotherapy sessions restored a range of cognitive functions, as

measured a month later via behavioral testing.

In contrast, animals that did not receive stem cells showed significant learning and memory impairment.

“Our findings provide the first solid evidence that transplantation of human neural stem cells can be used to reverse chemotherapeutic-induced damage of healthy tissue in the brain,” said study author Charles Limoli, PhD, of the University of California, Irvine.

For this study, Dr Limoli and his colleagues transplanted adult neural stem cells into the brains of rats that had received cyclophosphamide.

The cells migrated throughout the hippocampus, where they survived and differentiated into multiple neural cell types. Additionally, these cells triggered the secretion of neurotrophic growth factors that helped rebuild wounded neurons.

The investigators also found that engrafted cells protected the host neurons, thereby preventing the loss or promoting the repair of damaged neurons and their finer structural elements, referred to as dendritic spines.

“This research suggests that stem cell therapies may one day be implemented in the clinic to provide relief to patients suffering from cognitive impairments incurred as a result of their cancer treatments,” Dr Limoli said. “While much work remains, a clinical trial analyzing the safety of such approaches may be possible within a few years.”

Leukemia patient

Photo by Bill Branson

New research indicates that patients who undergo cranial radiotherapy (CRT) for pediatric cancer may have an increased risk of anterior pituitary deficits decades after they receive treatment.

The study also suggests these deficiencies often go undiagnosed, although they can impact health and quality of life.

These discoveries, reported in the Journal of Clinical Oncology, highlight the need for lifelong health screenings of pediatric cancer survivors, researchers say.

They studied 748 survivors of leukemia, brain, and other cancers, assessing the prevalence of and risk factors for growth hormone deficiency (GHD), luteinizing hormone/follicle-stimulating hormone deficiencies (LH/FSHD), thyroid-stimulating hormone deficiency (TSHD), and adrenocorticotropic hormone deficiency (ACTHD) after CRT.

The researchers observed survivors for a mean of 27.3 years (range, 10.8 to 47.7 years).

GHD was the most common deficiency, with an estimated point prevalence of 46.5%. The estimated point prevalence was 10.8% for LH/FSHD, 7.5% for TSHD, and 4% for ACTHD. The cumulative incidence of the deficiencies increased with follow-up.

Higher doses of CRT were associated with an increased risk of deficiencies. Doses of 22 to 29.9 Gy were significantly associated with GHD, doses of 22 Gy or higher were associated with LH/FSHD, and doses of 30 Gy or greater were associated with TSHD and ACTHD.

The researchers also found that male sex and obesity were significantly associated with LH/FSHD, and white race was significantly associated with LH/FSHD and TSHD.

GHD and LH/FSHD were the deficiencies that were most likely to be undiagnosed. GHD was not treated in 99.7% of affected survivors, and LH/FSHD was not treated in 78.5%.

There was an association between untreated GHD and reduced strength and muscle size, low energy, poor fitness, and abdominal obesity. Untreated LH/FSHD was associated with low bone mineral density, reduced fitness, high blood pressure, abdominal obesity, and elevated cholesterol and other blood lipids.

“This study provides much needed long-term follow-up data and shows that the risk of pituitary problems follows these survivors into adulthood,” said study author Wassim Chemaitilly, MD, of St Jude Children’s Research Center in Memphis, Tennessee.

“The findings also underscore the need for the nation’s growing population of childhood cancer survivors to get recommended health screenings, and the challenges they face in trying to navigate the healthcare system and follow that advice.”

Guidelines developed by the Children’s Oncology Group call for childhood cancer survivors treated with CRT to have their pituitary function checked annually. Dr Chemaitilly said the high percentage of survivors with previously undiagnosed hormone deficiencies in this study highlights the need for new strategies to ensure survivors receive recommended health checks.

He also said additional research is needed to help guide the management of adults with growth hormone deficiency. Treatment is expensive, and the long-term benefits in adults are uncertain.

Leukemia patient

Photo by Bill Branson

New research indicates that patients who undergo cranial radiotherapy (CRT) for pediatric cancer may have an increased risk of anterior pituitary deficits decades after they receive treatment.

The study also suggests these deficiencies often go undiagnosed, although they can impact health and quality of life.

These discoveries, reported in the Journal of Clinical Oncology, highlight the need for lifelong health screenings of pediatric cancer survivors, researchers say.

They studied 748 survivors of leukemia, brain, and other cancers, assessing the prevalence of and risk factors for growth hormone deficiency (GHD), luteinizing hormone/follicle-stimulating hormone deficiencies (LH/FSHD), thyroid-stimulating hormone deficiency (TSHD), and adrenocorticotropic hormone deficiency (ACTHD) after CRT.

The researchers observed survivors for a mean of 27.3 years (range, 10.8 to 47.7 years).

GHD was the most common deficiency, with an estimated point prevalence of 46.5%. The estimated point prevalence was 10.8% for LH/FSHD, 7.5% for TSHD, and 4% for ACTHD. The cumulative incidence of the deficiencies increased with follow-up.

Higher doses of CRT were associated with an increased risk of deficiencies. Doses of 22 to 29.9 Gy were significantly associated with GHD, doses of 22 Gy or higher were associated with LH/FSHD, and doses of 30 Gy or greater were associated with TSHD and ACTHD.

The researchers also found that male sex and obesity were significantly associated with LH/FSHD, and white race was significantly associated with LH/FSHD and TSHD.

GHD and LH/FSHD were the deficiencies that were most likely to be undiagnosed. GHD was not treated in 99.7% of affected survivors, and LH/FSHD was not treated in 78.5%.

There was an association between untreated GHD and reduced strength and muscle size, low energy, poor fitness, and abdominal obesity. Untreated LH/FSHD was associated with low bone mineral density, reduced fitness, high blood pressure, abdominal obesity, and elevated cholesterol and other blood lipids.

“This study provides much needed long-term follow-up data and shows that the risk of pituitary problems follows these survivors into adulthood,” said study author Wassim Chemaitilly, MD, of St Jude Children’s Research Center in Memphis, Tennessee.

“The findings also underscore the need for the nation’s growing population of childhood cancer survivors to get recommended health screenings, and the challenges they face in trying to navigate the healthcare system and follow that advice.”

Guidelines developed by the Children’s Oncology Group call for childhood cancer survivors treated with CRT to have their pituitary function checked annually. Dr Chemaitilly said the high percentage of survivors with previously undiagnosed hormone deficiencies in this study highlights the need for new strategies to ensure survivors receive recommended health checks.

He also said additional research is needed to help guide the management of adults with growth hormone deficiency. Treatment is expensive, and the long-term benefits in adults are uncertain.

Leukemia patient

Photo by Bill Branson

New research indicates that patients who undergo cranial radiotherapy (CRT) for pediatric cancer may have an increased risk of anterior pituitary deficits decades after they receive treatment.

The study also suggests these deficiencies often go undiagnosed, although they can impact health and quality of life.

These discoveries, reported in the Journal of Clinical Oncology, highlight the need for lifelong health screenings of pediatric cancer survivors, researchers say.

They studied 748 survivors of leukemia, brain, and other cancers, assessing the prevalence of and risk factors for growth hormone deficiency (GHD), luteinizing hormone/follicle-stimulating hormone deficiencies (LH/FSHD), thyroid-stimulating hormone deficiency (TSHD), and adrenocorticotropic hormone deficiency (ACTHD) after CRT.

The researchers observed survivors for a mean of 27.3 years (range, 10.8 to 47.7 years).

GHD was the most common deficiency, with an estimated point prevalence of 46.5%. The estimated point prevalence was 10.8% for LH/FSHD, 7.5% for TSHD, and 4% for ACTHD. The cumulative incidence of the deficiencies increased with follow-up.

Higher doses of CRT were associated with an increased risk of deficiencies. Doses of 22 to 29.9 Gy were significantly associated with GHD, doses of 22 Gy or higher were associated with LH/FSHD, and doses of 30 Gy or greater were associated with TSHD and ACTHD.

The researchers also found that male sex and obesity were significantly associated with LH/FSHD, and white race was significantly associated with LH/FSHD and TSHD.

GHD and LH/FSHD were the deficiencies that were most likely to be undiagnosed. GHD was not treated in 99.7% of affected survivors, and LH/FSHD was not treated in 78.5%.

There was an association between untreated GHD and reduced strength and muscle size, low energy, poor fitness, and abdominal obesity. Untreated LH/FSHD was associated with low bone mineral density, reduced fitness, high blood pressure, abdominal obesity, and elevated cholesterol and other blood lipids.

“This study provides much needed long-term follow-up data and shows that the risk of pituitary problems follows these survivors into adulthood,” said study author Wassim Chemaitilly, MD, of St Jude Children’s Research Center in Memphis, Tennessee.

“The findings also underscore the need for the nation’s growing population of childhood cancer survivors to get recommended health screenings, and the challenges they face in trying to navigate the healthcare system and follow that advice.”

Guidelines developed by the Children’s Oncology Group call for childhood cancer survivors treated with CRT to have their pituitary function checked annually. Dr Chemaitilly said the high percentage of survivors with previously undiagnosed hormone deficiencies in this study highlights the need for new strategies to ensure survivors receive recommended health checks.

He also said additional research is needed to help guide the management of adults with growth hormone deficiency. Treatment is expensive, and the long-term benefits in adults are uncertain.

Doctor consults with a cancer

patient and her father

Photo by Rhoda Baer

Results of 2 new studies indicate that young adults (ages 18 to 39) who have survived leukemia or lymphoma are more likely to report high distress than older survivors (age 65 and older).

Specifically, 45% of younger survivors reported moderate-to-high distress, whereas only 18% of older survivors reported similarly elevated levels.

In both groups, this distress was not affected by the amount of time since a patient received treatment. Distress was just as likely to be high in survivors who had completed treatment 4 years prior as in survivors who were 3 months out of treatment.

Whitney Jones, PhD, of the University of Colorado Denver, and her colleagues reported these findings in the Journal of Psychosocial Oncology.

In the first study, Dr Jones and her colleagues surveyed 477 cancer survivors, using a widely used measure of distress after trauma and several items from a measure of quality of life in cancer survivors.

These measures allowed the researchers to ask which factors of a cancer survivor’s life after treatment are the best predictors of persistent distress after treatment completion.

And results showed that survivors younger than 40 had the highest prevalence of distress.

Dr Jones explained the effect of age on distress using a framework called the Lifespan Perspective. Because there is an expected social, cultural, and developmental course of a person’s life, an event that is highly disruptive in one lifespan stage may be less disruptive in another.

“For younger survivors, cancer is out of context,” Dr Jones said. “When you’re under 40, you’re finishing your education, entering the workforce, starting a family, and cancer may be interpreted as disruptive and unexpected in that phase.”

“On the other hand, some of our older survivors said things like, ‘Cancer isn’t the most difficult thing I’ve experienced in life.’ And they knew friends and family members who had dealt with similar cancer experiences.”

The study also showed that people who feared recurrence were most likely to report high overall distress levels. And high financial burden due to cancer treatment predicted distress.

In the second study, the researchers used interviews with 51 leukemia and lymphoma survivors to explore the human side of these numbers and better understand the sources of distress as articulated by survivors themselves.

“For example, this was before the Affordable Care Act, and we had one survivor who talked about having only the basic college student insurance when he was diagnosed,” Dr Jones said. “After treatment, he discovered he had substantial medical debt and was uninsurable.”

“It helped to hear survivors talk about their experiences in their own words. To hear them articulate it helped us understand the real struggles behind our data.”

The interviews also helped to explain why distress lingers even years after treatment ends.

“A patient told us that, after lymphoma treatment, her doctor said that it would take 2 years to recover physically and mentally, and that almost all the gains would be in these 2 years,” Dr Jones said.

“She said something like, ‘I was really patient for 2 years, then after those 2 years passed, I didn’t feel any better and realized this is what I was going to be living with.’”

Distress detection and treatment is increasingly being seen as part of the standard of care for cancer patients and post-treatment survivors, the researchers noted.

For example, organizations like the National Comprehensive Cancer Network and the American College of Surgeons Commission on Cancer mandate distress screening and treatment in order to earn accreditation from these institutions.

“Understanding which individuals are most likely to experience elevated distress can be useful in targeting interventions to potential participants,” Dr Jones said.

Doctor consults with a cancer

patient and her father

Photo by Rhoda Baer

Results of 2 new studies indicate that young adults (ages 18 to 39) who have survived leukemia or lymphoma are more likely to report high distress than older survivors (age 65 and older).

Specifically, 45% of younger survivors reported moderate-to-high distress, whereas only 18% of older survivors reported similarly elevated levels.

In both groups, this distress was not affected by the amount of time since a patient received treatment. Distress was just as likely to be high in survivors who had completed treatment 4 years prior as in survivors who were 3 months out of treatment.

Whitney Jones, PhD, of the University of Colorado Denver, and her colleagues reported these findings in the Journal of Psychosocial Oncology.

In the first study, Dr Jones and her colleagues surveyed 477 cancer survivors, using a widely used measure of distress after trauma and several items from a measure of quality of life in cancer survivors.

These measures allowed the researchers to ask which factors of a cancer survivor’s life after treatment are the best predictors of persistent distress after treatment completion.

And results showed that survivors younger than 40 had the highest prevalence of distress.

Dr Jones explained the effect of age on distress using a framework called the Lifespan Perspective. Because there is an expected social, cultural, and developmental course of a person’s life, an event that is highly disruptive in one lifespan stage may be less disruptive in another.

“For younger survivors, cancer is out of context,” Dr Jones said. “When you’re under 40, you’re finishing your education, entering the workforce, starting a family, and cancer may be interpreted as disruptive and unexpected in that phase.”

“On the other hand, some of our older survivors said things like, ‘Cancer isn’t the most difficult thing I’ve experienced in life.’ And they knew friends and family members who had dealt with similar cancer experiences.”

The study also showed that people who feared recurrence were most likely to report high overall distress levels. And high financial burden due to cancer treatment predicted distress.

In the second study, the researchers used interviews with 51 leukemia and lymphoma survivors to explore the human side of these numbers and better understand the sources of distress as articulated by survivors themselves.

“For example, this was before the Affordable Care Act, and we had one survivor who talked about having only the basic college student insurance when he was diagnosed,” Dr Jones said. “After treatment, he discovered he had substantial medical debt and was uninsurable.”

“It helped to hear survivors talk about their experiences in their own words. To hear them articulate it helped us understand the real struggles behind our data.”

The interviews also helped to explain why distress lingers even years after treatment ends.

“A patient told us that, after lymphoma treatment, her doctor said that it would take 2 years to recover physically and mentally, and that almost all the gains would be in these 2 years,” Dr Jones said.

“She said something like, ‘I was really patient for 2 years, then after those 2 years passed, I didn’t feel any better and realized this is what I was going to be living with.’”

Distress detection and treatment is increasingly being seen as part of the standard of care for cancer patients and post-treatment survivors, the researchers noted.

For example, organizations like the National Comprehensive Cancer Network and the American College of Surgeons Commission on Cancer mandate distress screening and treatment in order to earn accreditation from these institutions.

“Understanding which individuals are most likely to experience elevated distress can be useful in targeting interventions to potential participants,” Dr Jones said.

Doctor consults with a cancer

patient and her father

Photo by Rhoda Baer

Results of 2 new studies indicate that young adults (ages 18 to 39) who have survived leukemia or lymphoma are more likely to report high distress than older survivors (age 65 and older).

Specifically, 45% of younger survivors reported moderate-to-high distress, whereas only 18% of older survivors reported similarly elevated levels.

In both groups, this distress was not affected by the amount of time since a patient received treatment. Distress was just as likely to be high in survivors who had completed treatment 4 years prior as in survivors who were 3 months out of treatment.

Whitney Jones, PhD, of the University of Colorado Denver, and her colleagues reported these findings in the Journal of Psychosocial Oncology.

In the first study, Dr Jones and her colleagues surveyed 477 cancer survivors, using a widely used measure of distress after trauma and several items from a measure of quality of life in cancer survivors.

These measures allowed the researchers to ask which factors of a cancer survivor’s life after treatment are the best predictors of persistent distress after treatment completion.

And results showed that survivors younger than 40 had the highest prevalence of distress.

Dr Jones explained the effect of age on distress using a framework called the Lifespan Perspective. Because there is an expected social, cultural, and developmental course of a person’s life, an event that is highly disruptive in one lifespan stage may be less disruptive in another.

“For younger survivors, cancer is out of context,” Dr Jones said. “When you’re under 40, you’re finishing your education, entering the workforce, starting a family, and cancer may be interpreted as disruptive and unexpected in that phase.”

“On the other hand, some of our older survivors said things like, ‘Cancer isn’t the most difficult thing I’ve experienced in life.’ And they knew friends and family members who had dealt with similar cancer experiences.”

The study also showed that people who feared recurrence were most likely to report high overall distress levels. And high financial burden due to cancer treatment predicted distress.

In the second study, the researchers used interviews with 51 leukemia and lymphoma survivors to explore the human side of these numbers and better understand the sources of distress as articulated by survivors themselves.

“For example, this was before the Affordable Care Act, and we had one survivor who talked about having only the basic college student insurance when he was diagnosed,” Dr Jones said. “After treatment, he discovered he had substantial medical debt and was uninsurable.”

“It helped to hear survivors talk about their experiences in their own words. To hear them articulate it helped us understand the real struggles behind our data.”

The interviews also helped to explain why distress lingers even years after treatment ends.

“A patient told us that, after lymphoma treatment, her doctor said that it would take 2 years to recover physically and mentally, and that almost all the gains would be in these 2 years,” Dr Jones said.

“She said something like, ‘I was really patient for 2 years, then after those 2 years passed, I didn’t feel any better and realized this is what I was going to be living with.’”

Distress detection and treatment is increasingly being seen as part of the standard of care for cancer patients and post-treatment survivors, the researchers noted.

For example, organizations like the National Comprehensive Cancer Network and the American College of Surgeons Commission on Cancer mandate distress screening and treatment in order to earn accreditation from these institutions.

“Understanding which individuals are most likely to experience elevated distress can be useful in targeting interventions to potential participants,” Dr Jones said.

Doctor consults with a patient

Photo courtesy of NIH

Although it makes sense that patient requests might drive physicians to practice defensive medicine, new research suggests that may not be the case with cancer patients.

The study, conducted at outpatient oncology centers, showed that patients rarely made clinically inappropriate requests.

Only 1% of more than 5000 patient-clinician encounters resulted in a clinically inappropriate request. And physicians rarely complied with these requests.

Keerthi Gogineni, MD, of the Hospital of the University of Pennsylvania in Philadelphia, and colleagues  reported these findings in JAMA Oncology.

The researchers analyzed interviews with clinicians immediately after they visited with patients to assess whether a patient had made a request, the type of request made, and the clinical appropriateness of it.

The interviews were conducted at outpatient oncology facilities at 3 Philadelphia-area hospitals between October 2013 and June 2014.

The authors evaluated 5050 patient-clinician encounters involving 3624 patients and 60 clinicians. Most of the patients were women, and the most common cancer was hematologic.

Overall, 440 (8.7%) of the encounters included a patient demand or request, such as for imaging studies, treatments, or tests. And physicians complied with 365 (83%) of them.

Of all the patient-clinician encounters, 50 (1%) included a clinically inappropriate request. Clinicians complied with 7 of them. So, in 0.14% of encounters, clinicians ordered a test or treatment based on a clinically inappropriate request.

“At least in oncology, ‘demanding patients’ seem infrequent and may not account for a significant proportion of costs,” the researchers concluded.

In a related editorial, Anthony L. Back, MD, of the Seattle Cancer Care Alliance in Washington, wrote that inappropriate patient demands appear to be “more mythical than real.”

“[W]e have to stop blaming patients for being demanding,” he wrote. “In reality, it is hardly happening. The myth of the demanding patient is more about our own responses and how lackluster communication skills can contribute to difficult situations that stick in our throats and in our memories. And when we have calmed down enough to look up, we see that what is really happening between patients and physicians these days is something quite different.”

“It is possible that what the study by Gogineni et al documents is a point in the evolution of the patient-physician relationship when both sides recognize the complexity of cancer care belies a simple fix. Perhaps this ‘negative’ study is pointing to an important truth: that we need to redirect our attention from the myths that are distracting us.”

Doctor consults with a patient

Photo courtesy of NIH

Although it makes sense that patient requests might drive physicians to practice defensive medicine, new research suggests that may not be the case with cancer patients.

The study, conducted at outpatient oncology centers, showed that patients rarely made clinically inappropriate requests.

Only 1% of more than 5000 patient-clinician encounters resulted in a clinically inappropriate request. And physicians rarely complied with these requests.

Keerthi Gogineni, MD, of the Hospital of the University of Pennsylvania in Philadelphia, and colleagues  reported these findings in JAMA Oncology.

The researchers analyzed interviews with clinicians immediately after they visited with patients to assess whether a patient had made a request, the type of request made, and the clinical appropriateness of it.

The interviews were conducted at outpatient oncology facilities at 3 Philadelphia-area hospitals between October 2013 and June 2014.

The authors evaluated 5050 patient-clinician encounters involving 3624 patients and 60 clinicians. Most of the patients were women, and the most common cancer was hematologic.

Overall, 440 (8.7%) of the encounters included a patient demand or request, such as for imaging studies, treatments, or tests. And physicians complied with 365 (83%) of them.

Of all the patient-clinician encounters, 50 (1%) included a clinically inappropriate request. Clinicians complied with 7 of them. So, in 0.14% of encounters, clinicians ordered a test or treatment based on a clinically inappropriate request.

“At least in oncology, ‘demanding patients’ seem infrequent and may not account for a significant proportion of costs,” the researchers concluded.

In a related editorial, Anthony L. Back, MD, of the Seattle Cancer Care Alliance in Washington, wrote that inappropriate patient demands appear to be “more mythical than real.”

“[W]e have to stop blaming patients for being demanding,” he wrote. “In reality, it is hardly happening. The myth of the demanding patient is more about our own responses and how lackluster communication skills can contribute to difficult situations that stick in our throats and in our memories. And when we have calmed down enough to look up, we see that what is really happening between patients and physicians these days is something quite different.”

“It is possible that what the study by Gogineni et al documents is a point in the evolution of the patient-physician relationship when both sides recognize the complexity of cancer care belies a simple fix. Perhaps this ‘negative’ study is pointing to an important truth: that we need to redirect our attention from the myths that are distracting us.”

Doctor consults with a patient

Photo courtesy of NIH

Although it makes sense that patient requests might drive physicians to practice defensive medicine, new research suggests that may not be the case with cancer patients.

The study, conducted at outpatient oncology centers, showed that patients rarely made clinically inappropriate requests.

Only 1% of more than 5000 patient-clinician encounters resulted in a clinically inappropriate request. And physicians rarely complied with these requests.

Keerthi Gogineni, MD, of the Hospital of the University of Pennsylvania in Philadelphia, and colleagues  reported these findings in JAMA Oncology.

The researchers analyzed interviews with clinicians immediately after they visited with patients to assess whether a patient had made a request, the type of request made, and the clinical appropriateness of it.

The interviews were conducted at outpatient oncology facilities at 3 Philadelphia-area hospitals between October 2013 and June 2014.

The authors evaluated 5050 patient-clinician encounters involving 3624 patients and 60 clinicians. Most of the patients were women, and the most common cancer was hematologic.

Overall, 440 (8.7%) of the encounters included a patient demand or request, such as for imaging studies, treatments, or tests. And physicians complied with 365 (83%) of them.

Of all the patient-clinician encounters, 50 (1%) included a clinically inappropriate request. Clinicians complied with 7 of them. So, in 0.14% of encounters, clinicians ordered a test or treatment based on a clinically inappropriate request.

“At least in oncology, ‘demanding patients’ seem infrequent and may not account for a significant proportion of costs,” the researchers concluded.

In a related editorial, Anthony L. Back, MD, of the Seattle Cancer Care Alliance in Washington, wrote that inappropriate patient demands appear to be “more mythical than real.”

“[W]e have to stop blaming patients for being demanding,” he wrote. “In reality, it is hardly happening. The myth of the demanding patient is more about our own responses and how lackluster communication skills can contribute to difficult situations that stick in our throats and in our memories. And when we have calmed down enough to look up, we see that what is really happening between patients and physicians these days is something quite different.”

“It is possible that what the study by Gogineni et al documents is a point in the evolution of the patient-physician relationship when both sides recognize the complexity of cancer care belies a simple fix. Perhaps this ‘negative’ study is pointing to an important truth: that we need to redirect our attention from the myths that are distracting us.”

Doctor holding a clipboard

Researchers have identified 8 highly specific physical and cognitive signs that seem to be associated with imminent death in cancer patients.

The findings, published in Cancer, could offer clinicians the ability to better communicate with patients and their families.

The research might also help guide the medical team and caregivers when it comes to complex decision making, such as discontinuing tests and therapy, plans for hospital discharge, and hospice referral.

Previous studies in end-of-life care have focused on physicians prognosticating better. However, research on how to tell if a patient has entered the final days of life has been minimal, according to David Hui, MD, of the University of Texas MD Anderson Cancer Center in Houston.

“In the past, studies trying to understand the signs associated with impending death were conducted in people who were recognized as dying, so there’s a potential bias built into this model,” Dr Hui said.

“With our study, we observed a list of signs in patients from the time they were admitted to the palliative care unit. They were observed systematically, twice a day, without knowing if the patient would die or be discharged.”

Dr Hui and his colleagues observed 357 cancer patients, 57% of whom ultimately died. The researchers observed 52 physical and cognitive signs—identified by Dr Hui and his colleagues in previous research—twice a day from the patient’s admission to discharge or death.

Of those 52 signs, the 8 most highly associated with impending death within 3 days were:

• Nonreactive pupils
• Decreased response to verbal stimuli
• Decreased response to visual stimuli
• Inability to close eyelids
• Drooping of the nasolabial fold
• Neck hyperextension
• Grunting of vocal cords
• Upper gastrointestinal bleeding.

“When cancer patients reach the last days of life, this is an extremely emotional time for families; their stress levels cannot be understated,” Dr Hui said.

“Knowing when death is imminent would provide more information so caregivers can plan appropriately. For clinicians, having this information could help reassure families that we are providing the best care possible.”

Dr Hui stressed that this research is not yet practice-changing, but is an important step in understanding these 8 signs and their relation to impending death. In addition, the findings are only representative of imminent cancer death and should not be generalized to other causes of death.

Follow-up studies in different settings are planned. Dr Hui and his colleagues plan to look at the reliability of the identified signs, as well as evaluate this research in other countries and in the hospice setting.

Doctor holding a clipboard

Researchers have identified 8 highly specific physical and cognitive signs that seem to be associated with imminent death in cancer patients.

The findings, published in Cancer, could offer clinicians the ability to better communicate with patients and their families.

The research might also help guide the medical team and caregivers when it comes to complex decision making, such as discontinuing tests and therapy, plans for hospital discharge, and hospice referral.

Previous studies in end-of-life care have focused on physicians prognosticating better. However, research on how to tell if a patient has entered the final days of life has been minimal, according to David Hui, MD, of the University of Texas MD Anderson Cancer Center in Houston.

“In the past, studies trying to understand the signs associated with impending death were conducted in people who were recognized as dying, so there’s a potential bias built into this model,” Dr Hui said.

“With our study, we observed a list of signs in patients from the time they were admitted to the palliative care unit. They were observed systematically, twice a day, without knowing if the patient would die or be discharged.”

Dr Hui and his colleagues observed 357 cancer patients, 57% of whom ultimately died. The researchers observed 52 physical and cognitive signs—identified by Dr Hui and his colleagues in previous research—twice a day from the patient’s admission to discharge or death.

Of those 52 signs, the 8 most highly associated with impending death within 3 days were:

• Nonreactive pupils
• Decreased response to verbal stimuli
• Decreased response to visual stimuli
• Inability to close eyelids
• Drooping of the nasolabial fold
• Neck hyperextension
• Grunting of vocal cords
• Upper gastrointestinal bleeding.

“When cancer patients reach the last days of life, this is an extremely emotional time for families; their stress levels cannot be understated,” Dr Hui said.

“Knowing when death is imminent would provide more information so caregivers can plan appropriately. For clinicians, having this information could help reassure families that we are providing the best care possible.”

Dr Hui stressed that this research is not yet practice-changing, but is an important step in understanding these 8 signs and their relation to impending death. In addition, the findings are only representative of imminent cancer death and should not be generalized to other causes of death.

Follow-up studies in different settings are planned. Dr Hui and his colleagues plan to look at the reliability of the identified signs, as well as evaluate this research in other countries and in the hospice setting.

Doctor holding a clipboard

Researchers have identified 8 highly specific physical and cognitive signs that seem to be associated with imminent death in cancer patients.

The findings, published in Cancer, could offer clinicians the ability to better communicate with patients and their families.

The research might also help guide the medical team and caregivers when it comes to complex decision making, such as discontinuing tests and therapy, plans for hospital discharge, and hospice referral.

Previous studies in end-of-life care have focused on physicians prognosticating better. However, research on how to tell if a patient has entered the final days of life has been minimal, according to David Hui, MD, of the University of Texas MD Anderson Cancer Center in Houston.

“In the past, studies trying to understand the signs associated with impending death were conducted in people who were recognized as dying, so there’s a potential bias built into this model,” Dr Hui said.

“With our study, we observed a list of signs in patients from the time they were admitted to the palliative care unit. They were observed systematically, twice a day, without knowing if the patient would die or be discharged.”

Dr Hui and his colleagues observed 357 cancer patients, 57% of whom ultimately died. The researchers observed 52 physical and cognitive signs—identified by Dr Hui and his colleagues in previous research—twice a day from the patient’s admission to discharge or death.

Of those 52 signs, the 8 most highly associated with impending death within 3 days were:

• Nonreactive pupils
• Decreased response to verbal stimuli
• Decreased response to visual stimuli
• Inability to close eyelids
• Drooping of the nasolabial fold
• Neck hyperextension
• Grunting of vocal cords
• Upper gastrointestinal bleeding.

“When cancer patients reach the last days of life, this is an extremely emotional time for families; their stress levels cannot be understated,” Dr Hui said.

“Knowing when death is imminent would provide more information so caregivers can plan appropriately. For clinicians, having this information could help reassure families that we are providing the best care possible.”

Dr Hui stressed that this research is not yet practice-changing, but is an important step in understanding these 8 signs and their relation to impending death. In addition, the findings are only representative of imminent cancer death and should not be generalized to other causes of death.

Follow-up studies in different settings are planned. Dr Hui and his colleagues plan to look at the reliability of the identified signs, as well as evaluate this research in other countries and in the hospice setting.

Prescription medications

Photo courtesy of CDC

New research indicates that a tyrosine kinase inhibitor (TKI) approved to treat advanced renal cell carcinoma could prove useful in treating patients with drug-resistant chronic myeloid leukemia (CML) or acute lymphoblastic leukemia (ALL).

The study showed that the TKI, axitinib, can inhibit BCR-ABL1 (T315I), a mutation known to confer drug resistance in CML and ALL.

“Since axitinib is already used to treat cancer, its safety is known,” said Kimmo Porkka, MD, PhD, of the University of Helsinki in Finland.

“[A] formal exploration of its clinical utility in drug-resistant leukemia can now be done in a fast-track mode. Thus, the normally very long path from lab bench to bedside is now significantly shortened.”

Dr Porkka and his colleagues described the newfound activity of axitinib in Nature.

The researchers used a drug sensitivity and resistance testing method developed at the University of Helsinki’s Institute for Molecular Medicine Finland (FIMM) to examine how patient-derived leukemia cells responded to a large panel of drugs.

In this way, the group identified axitinib as a promising drug candidate for CML and ALL. Axitinib effectively eliminated drug-resistant leukemia cells.

The TKI inhibited BCR-ABL1 (T315I) at biochemical and cellular levels by binding to the active form of ABL1 (T315I) in a mutation-selective binding mode.

The researchers said this suggests the T315I mutation shifts the conformational equilibrium of the kinase in favor of an active (DFG-in) A-loop conformation, which has more optimal binding interactions with axitinib.

“If you think of the targeted protein as a lock into which the cancer drug fits in as a key, the resistant protein changes in such a way that we need a different key,” said study author Brion Murray, PhD, of Pfizer Worldwide Research & Development in San Diego, California.

“In the case of axitinib, it acts as two distinct keys—one for renal cell carcinoma and one for leukemia.”

The researchers also treated a CML patient with axitinib and observed a “rapid reduction” of T315I-positive cells in the patient’s bone marrow.

“Further research will determine whether these findings have the potential to significantly improve the standard of care for this select group of CML patients and patients with other related leukemias,” Dr Murray concluded.

Prescription medications

Photo courtesy of CDC

New research indicates that a tyrosine kinase inhibitor (TKI) approved to treat advanced renal cell carcinoma could prove useful in treating patients with drug-resistant chronic myeloid leukemia (CML) or acute lymphoblastic leukemia (ALL).

The study showed that the TKI, axitinib, can inhibit BCR-ABL1 (T315I), a mutation known to confer drug resistance in CML and ALL.

“Since axitinib is already used to treat cancer, its safety is known,” said Kimmo Porkka, MD, PhD, of the University of Helsinki in Finland.

“[A] formal exploration of its clinical utility in drug-resistant leukemia can now be done in a fast-track mode. Thus, the normally very long path from lab bench to bedside is now significantly shortened.”

Dr Porkka and his colleagues described the newfound activity of axitinib in Nature.

The researchers used a drug sensitivity and resistance testing method developed at the University of Helsinki’s Institute for Molecular Medicine Finland (FIMM) to examine how patient-derived leukemia cells responded to a large panel of drugs.

In this way, the group identified axitinib as a promising drug candidate for CML and ALL. Axitinib effectively eliminated drug-resistant leukemia cells.

The TKI inhibited BCR-ABL1 (T315I) at biochemical and cellular levels by binding to the active form of ABL1 (T315I) in a mutation-selective binding mode.

The researchers said this suggests the T315I mutation shifts the conformational equilibrium of the kinase in favor of an active (DFG-in) A-loop conformation, which has more optimal binding interactions with axitinib.

“If you think of the targeted protein as a lock into which the cancer drug fits in as a key, the resistant protein changes in such a way that we need a different key,” said study author Brion Murray, PhD, of Pfizer Worldwide Research & Development in San Diego, California.

“In the case of axitinib, it acts as two distinct keys—one for renal cell carcinoma and one for leukemia.”

The researchers also treated a CML patient with axitinib and observed a “rapid reduction” of T315I-positive cells in the patient’s bone marrow.

“Further research will determine whether these findings have the potential to significantly improve the standard of care for this select group of CML patients and patients with other related leukemias,” Dr Murray concluded.

Prescription medications

Photo courtesy of CDC

New research indicates that a tyrosine kinase inhibitor (TKI) approved to treat advanced renal cell carcinoma could prove useful in treating patients with drug-resistant chronic myeloid leukemia (CML) or acute lymphoblastic leukemia (ALL).

The study showed that the TKI, axitinib, can inhibit BCR-ABL1 (T315I), a mutation known to confer drug resistance in CML and ALL.

“Since axitinib is already used to treat cancer, its safety is known,” said Kimmo Porkka, MD, PhD, of the University of Helsinki in Finland.

“[A] formal exploration of its clinical utility in drug-resistant leukemia can now be done in a fast-track mode. Thus, the normally very long path from lab bench to bedside is now significantly shortened.”

Dr Porkka and his colleagues described the newfound activity of axitinib in Nature.

The researchers used a drug sensitivity and resistance testing method developed at the University of Helsinki’s Institute for Molecular Medicine Finland (FIMM) to examine how patient-derived leukemia cells responded to a large panel of drugs.

In this way, the group identified axitinib as a promising drug candidate for CML and ALL. Axitinib effectively eliminated drug-resistant leukemia cells.

The TKI inhibited BCR-ABL1 (T315I) at biochemical and cellular levels by binding to the active form of ABL1 (T315I) in a mutation-selective binding mode.

The researchers said this suggests the T315I mutation shifts the conformational equilibrium of the kinase in favor of an active (DFG-in) A-loop conformation, which has more optimal binding interactions with axitinib.

“If you think of the targeted protein as a lock into which the cancer drug fits in as a key, the resistant protein changes in such a way that we need a different key,” said study author Brion Murray, PhD, of Pfizer Worldwide Research & Development in San Diego, California.

“In the case of axitinib, it acts as two distinct keys—one for renal cell carcinoma and one for leukemia.”

The researchers also treated a CML patient with axitinib and observed a “rapid reduction” of T315I-positive cells in the patient’s bone marrow.

“Further research will determine whether these findings have the potential to significantly improve the standard of care for this select group of CML patients and patients with other related leukemias,” Dr Murray concluded.

Bertie Gottgens, PhD

Photo courtesy of

University of Cambridge

A new computer model that simulates blood cell development could aid the discovery of novel treatments for hematologic malignancies, according to researchers.

“With this new computer model, we can carry out simulated experiments in seconds that would take many weeks to perform in the laboratory, dramatically speeding up research into blood development and the genetic mutations that cause leukemia,” said Bertie Gottgens, PhD, of the University of Cambridge in the UK.

Dr Gottgens and his colleagues explained this research in Nature Biotechnology.

To start, the researchers measured the activity of 48 genes in 3934 hematopoietic progenitor cells. They used the resulting dataset to construct the computer model of blood cell development, using computational approaches originally developed at Microsoft Research for the synthesis of computer code.

Subsequent lab experiments validated the accuracy of the model.

The researchers noted that the model can be used to simulate the activity of key genes implicated in hematologic malignancies. For example, around 1 in 5 children who develop leukemia have a faulty version of the RUNX1 gene, as do a similar proportion of adults with acute myeloid leukemia.

The computer model shows how RUNX1 interacts with other genes to control blood cell development. The gene produces the RUNX1 protein, which, in healthy patients, activates a network of key genes. In leukemia patients, an altered form of the protein is thought to suppress the network.

If the researchers change the “rules” in the network model, they can simulate the formation of abnormal leukemia cells. By tweaking the leukemia model until the behavior of the network reverts back to normal, the team can identify pathways that, potentially, could be targeted with drugs.

“Because the computer simulations are very fast, we can quickly screen through lots of possibilities to pick the most promising ones as pathways for drug development,” Dr Gottgens said.

“The cost of developing a new drug is enormous, and much of this cost comes from new candidate drugs failing late in the drug development process. Our model could significantly reduce the risk of failure, with the potential to make drug discovery faster and cheaper.”

Bertie Gottgens, PhD

Photo courtesy of

University of Cambridge

A new computer model that simulates blood cell development could aid the discovery of novel treatments for hematologic malignancies, according to researchers.

“With this new computer model, we can carry out simulated experiments in seconds that would take many weeks to perform in the laboratory, dramatically speeding up research into blood development and the genetic mutations that cause leukemia,” said Bertie Gottgens, PhD, of the University of Cambridge in the UK.

Dr Gottgens and his colleagues explained this research in Nature Biotechnology.

To start, the researchers measured the activity of 48 genes in 3934 hematopoietic progenitor cells. They used the resulting dataset to construct the computer model of blood cell development, using computational approaches originally developed at Microsoft Research for the synthesis of computer code.

Subsequent lab experiments validated the accuracy of the model.

The researchers noted that the model can be used to simulate the activity of key genes implicated in hematologic malignancies. For example, around 1 in 5 children who develop leukemia have a faulty version of the RUNX1 gene, as do a similar proportion of adults with acute myeloid leukemia.

The computer model shows how RUNX1 interacts with other genes to control blood cell development. The gene produces the RUNX1 protein, which, in healthy patients, activates a network of key genes. In leukemia patients, an altered form of the protein is thought to suppress the network.

If the researchers change the “rules” in the network model, they can simulate the formation of abnormal leukemia cells. By tweaking the leukemia model until the behavior of the network reverts back to normal, the team can identify pathways that, potentially, could be targeted with drugs.

“Because the computer simulations are very fast, we can quickly screen through lots of possibilities to pick the most promising ones as pathways for drug development,” Dr Gottgens said.

“The cost of developing a new drug is enormous, and much of this cost comes from new candidate drugs failing late in the drug development process. Our model could significantly reduce the risk of failure, with the potential to make drug discovery faster and cheaper.”

Bertie Gottgens, PhD

Photo courtesy of

University of Cambridge

A new computer model that simulates blood cell development could aid the discovery of novel treatments for hematologic malignancies, according to researchers.

“With this new computer model, we can carry out simulated experiments in seconds that would take many weeks to perform in the laboratory, dramatically speeding up research into blood development and the genetic mutations that cause leukemia,” said Bertie Gottgens, PhD, of the University of Cambridge in the UK.

Dr Gottgens and his colleagues explained this research in Nature Biotechnology.

To start, the researchers measured the activity of 48 genes in 3934 hematopoietic progenitor cells. They used the resulting dataset to construct the computer model of blood cell development, using computational approaches originally developed at Microsoft Research for the synthesis of computer code.

Subsequent lab experiments validated the accuracy of the model.

The researchers noted that the model can be used to simulate the activity of key genes implicated in hematologic malignancies. For example, around 1 in 5 children who develop leukemia have a faulty version of the RUNX1 gene, as do a similar proportion of adults with acute myeloid leukemia.

The computer model shows how RUNX1 interacts with other genes to control blood cell development. The gene produces the RUNX1 protein, which, in healthy patients, activates a network of key genes. In leukemia patients, an altered form of the protein is thought to suppress the network.

If the researchers change the “rules” in the network model, they can simulate the formation of abnormal leukemia cells. By tweaking the leukemia model until the behavior of the network reverts back to normal, the team can identify pathways that, potentially, could be targeted with drugs.

“Because the computer simulations are very fast, we can quickly screen through lots of possibilities to pick the most promising ones as pathways for drug development,” Dr Gottgens said.

“The cost of developing a new drug is enormous, and much of this cost comes from new candidate drugs failing late in the drug development process. Our model could significantly reduce the risk of failure, with the potential to make drug discovery faster and cheaper.”

Drugs in vials

Photo by Bill Branson

A new analysis indicates that certain high-cost therapies for hematologic malignancies provide reasonable value for money spent.

Most cost-effectiveness ratios were lower than thresholds commonly used to establish cost-effectiveness in the US—$50,000 or $100,000 per quality-adjusted life year (QALY) gained.

The median cost-effectiveness ratio was highest for chronic myeloid leukemia (CML), at $55,000/QALY, and lowest for non-Hodgkin lymphoma (NHL), at $21,500/QALY.

Researchers presented these data in Blood.

“Given the increased discussion about the high cost of these treatments, we were somewhat surprised to discover that their cost-effectiveness ratios were lower than expected,” said study author Peter J. Neumann, ScD, of Tufts Medical Center in Boston.

“Our analysis had a small sample size and included both industry- and non-industry-funded studies. In addition, cost-effectiveness ratios may have changed over time as associated costs or benefits have changed. However, the study underscores that debates in healthcare should consider the value of breakthrough drugs and not just costs.”

With that issue in mind, Dr Neumann and his colleagues had conducted a systematic review of studies published between 1996 and 2012 that examined the cost utility of agents for hematologic malignancies. The cost utility of a drug was depicted as a ratio of a drug’s total cost per patient QALY gained.

The researchers identified 29 studies, 22 of which were industry-funded. Nine studies were conducted from a US perspective, 6 from the UK, 3 from Norway, 3 from Sweden, 2 from France, 1 from Canada, 1 from Finland, and 4 from “other” countries.

The team grouped studies according to malignancy—CML, chronic lymphocytic leukemia (CLL), NHL, and multiple myeloma (MM)—as well as by treatment—α interferon, alemtuzumab, bendamustine, bortezomib, dasatinib, imatinib, lenalidomide, rituximab alone or in combination, and thalidomide.

The studies reported 44 cost-effectiveness ratios, most concerning interventions for NHL (41%) or CML (30%). Most ratios pertained to rituximab (43%), α interferon (18%), or imatinib (16%), and the most common intervention-disease combination was rituximab (alone or in combination) for NHL (36%).

The median cost-effectiveness ratios fluctuated over time, rising from $35,000/QALY (1996-2002) to $52,000/QALY (2003-2006), then falling to $22,000/QALY (2007-2012).

The median cost-effectiveness ratio reported by industry-funded studies was lower ($26,000/QALY) than for non-industry-funded studies ($33,000/QALY).

Four cost-effectiveness ratios, 1 from an industry-funded study, exceeded $100,000/QALY. This included 2 studies of bortezomib in MM, 1 of α interferon in CML, and 1 of imatinib in CML.

The researchers said these results suggest that many new treatments for hematologic malignancies may confer reasonable value for money spent. The distribution of cost-effectiveness ratios is comparable to those for cancers overall and for other healthcare fields, they said.

This study was funded by internal resources at the Center for the Evaluation of Value and Risk in Health. The center receives funding from federal, private foundation, and pharmaceutical industry sources.

Drugs in vials

Photo by Bill Branson

A new analysis indicates that certain high-cost therapies for hematologic malignancies provide reasonable value for money spent.

Most cost-effectiveness ratios were lower than thresholds commonly used to establish cost-effectiveness in the US—$50,000 or $100,000 per quality-adjusted life year (QALY) gained.

The median cost-effectiveness ratio was highest for chronic myeloid leukemia (CML), at $55,000/QALY, and lowest for non-Hodgkin lymphoma (NHL), at $21,500/QALY.

Researchers presented these data in Blood.

“Given the increased discussion about the high cost of these treatments, we were somewhat surprised to discover that their cost-effectiveness ratios were lower than expected,” said study author Peter J. Neumann, ScD, of Tufts Medical Center in Boston.

“Our analysis had a small sample size and included both industry- and non-industry-funded studies. In addition, cost-effectiveness ratios may have changed over time as associated costs or benefits have changed. However, the study underscores that debates in healthcare should consider the value of breakthrough drugs and not just costs.”

With that issue in mind, Dr Neumann and his colleagues had conducted a systematic review of studies published between 1996 and 2012 that examined the cost utility of agents for hematologic malignancies. The cost utility of a drug was depicted as a ratio of a drug’s total cost per patient QALY gained.

The researchers identified 29 studies, 22 of which were industry-funded. Nine studies were conducted from a US perspective, 6 from the UK, 3 from Norway, 3 from Sweden, 2 from France, 1 from Canada, 1 from Finland, and 4 from “other” countries.

The team grouped studies according to malignancy—CML, chronic lymphocytic leukemia (CLL), NHL, and multiple myeloma (MM)—as well as by treatment—α interferon, alemtuzumab, bendamustine, bortezomib, dasatinib, imatinib, lenalidomide, rituximab alone or in combination, and thalidomide.

The studies reported 44 cost-effectiveness ratios, most concerning interventions for NHL (41%) or CML (30%). Most ratios pertained to rituximab (43%), α interferon (18%), or imatinib (16%), and the most common intervention-disease combination was rituximab (alone or in combination) for NHL (36%).

The median cost-effectiveness ratios fluctuated over time, rising from $35,000/QALY (1996-2002) to $52,000/QALY (2003-2006), then falling to $22,000/QALY (2007-2012).

The median cost-effectiveness ratio reported by industry-funded studies was lower ($26,000/QALY) than for non-industry-funded studies ($33,000/QALY).

Four cost-effectiveness ratios, 1 from an industry-funded study, exceeded $100,000/QALY. This included 2 studies of bortezomib in MM, 1 of α interferon in CML, and 1 of imatinib in CML.

The researchers said these results suggest that many new treatments for hematologic malignancies may confer reasonable value for money spent. The distribution of cost-effectiveness ratios is comparable to those for cancers overall and for other healthcare fields, they said.

This study was funded by internal resources at the Center for the Evaluation of Value and Risk in Health. The center receives funding from federal, private foundation, and pharmaceutical industry sources.

Drugs in vials

Photo by Bill Branson

A new analysis indicates that certain high-cost therapies for hematologic malignancies provide reasonable value for money spent.

Most cost-effectiveness ratios were lower than thresholds commonly used to establish cost-effectiveness in the US—$50,000 or $100,000 per quality-adjusted life year (QALY) gained.

The median cost-effectiveness ratio was highest for chronic myeloid leukemia (CML), at $55,000/QALY, and lowest for non-Hodgkin lymphoma (NHL), at $21,500/QALY.

Researchers presented these data in Blood.

“Given the increased discussion about the high cost of these treatments, we were somewhat surprised to discover that their cost-effectiveness ratios were lower than expected,” said study author Peter J. Neumann, ScD, of Tufts Medical Center in Boston.

“Our analysis had a small sample size and included both industry- and non-industry-funded studies. In addition, cost-effectiveness ratios may have changed over time as associated costs or benefits have changed. However, the study underscores that debates in healthcare should consider the value of breakthrough drugs and not just costs.”

With that issue in mind, Dr Neumann and his colleagues had conducted a systematic review of studies published between 1996 and 2012 that examined the cost utility of agents for hematologic malignancies. The cost utility of a drug was depicted as a ratio of a drug’s total cost per patient QALY gained.

The researchers identified 29 studies, 22 of which were industry-funded. Nine studies were conducted from a US perspective, 6 from the UK, 3 from Norway, 3 from Sweden, 2 from France, 1 from Canada, 1 from Finland, and 4 from “other” countries.

The team grouped studies according to malignancy—CML, chronic lymphocytic leukemia (CLL), NHL, and multiple myeloma (MM)—as well as by treatment—α interferon, alemtuzumab, bendamustine, bortezomib, dasatinib, imatinib, lenalidomide, rituximab alone or in combination, and thalidomide.

The studies reported 44 cost-effectiveness ratios, most concerning interventions for NHL (41%) or CML (30%). Most ratios pertained to rituximab (43%), α interferon (18%), or imatinib (16%), and the most common intervention-disease combination was rituximab (alone or in combination) for NHL (36%).

The median cost-effectiveness ratios fluctuated over time, rising from $35,000/QALY (1996-2002) to $52,000/QALY (2003-2006), then falling to $22,000/QALY (2007-2012).

The median cost-effectiveness ratio reported by industry-funded studies was lower ($26,000/QALY) than for non-industry-funded studies ($33,000/QALY).

Four cost-effectiveness ratios, 1 from an industry-funded study, exceeded $100,000/QALY. This included 2 studies of bortezomib in MM, 1 of α interferon in CML, and 1 of imatinib in CML.

The researchers said these results suggest that many new treatments for hematologic malignancies may confer reasonable value for money spent. The distribution of cost-effectiveness ratios is comparable to those for cancers overall and for other healthcare fields, they said.

This study was funded by internal resources at the Center for the Evaluation of Value and Risk in Health. The center receives funding from federal, private foundation, and pharmaceutical industry sources.

CLL in the bone marrow

The genetic variability of chronic lymphocytic leukemia (CLL) appears to predict its aggressiveness, according to a study published in Genome Medicine.

Investigators found evidence suggesting that greater variability in gene expression is associated with more aggressive disease.

The team analyzed gene expression in two cohorts of CLL patients—those with IgVH mutations and a good prognosis and those with unmutated CLL who have more aggressive disease.

The researchers examined 70 mutated and 52 unmutated CLL samples, as well as 20 control samples taken from healthy individuals.

Unmutated, aggressive CLL showed increased gene expression variability across individuals, whereas gene expression variability was lower in less aggressive, mutated CLL.

The investigators validated these observations by comparing them against a second sample group consisting of 24 mutated and 36 unmutated CLL samples.

The results suggested that CLL aggressiveness is specifically determined by a set of 500 genes showing increased expression variability across individuals. The genes are involved in processes such as adaptation to the environment, cell death, tumor growth, and drug resistance.

“Our conclusion is that the coefficient of variation for gene expression in CLL efficiently predicts its aggressiveness,” said study author Alfonso Valencia, PhD, of Centro Nacional de Investigaciones Oncologicas (CNIO) in Madrid, Spain.

“More importantly, if further research confirms these findings, a classifier based on the measurement of gene expression variability could be created to predict the disease subtype of CLL patients.”

The researchers said their next step is to discover the mechanisms responsible for the high levels of expression variability for a given gene across individuals.

Understanding the mechanisms underlying this phenomenon is of crucial relevance for oncology research, the investigators said, as it is linked to tumor heterogeneity, a key feature of cancer progression and drug resistance.

The greater the genetic variability in a tumor, the better it will adapt to its environment, and the more probabilities for this tumor to spread, develop resistance to cancer therapies, and metastasize to distant organs.

CLL in the bone marrow

The genetic variability of chronic lymphocytic leukemia (CLL) appears to predict its aggressiveness, according to a study published in Genome Medicine.

Investigators found evidence suggesting that greater variability in gene expression is associated with more aggressive disease.

The team analyzed gene expression in two cohorts of CLL patients—those with IgVH mutations and a good prognosis and those with unmutated CLL who have more aggressive disease.

The researchers examined 70 mutated and 52 unmutated CLL samples, as well as 20 control samples taken from healthy individuals.

Unmutated, aggressive CLL showed increased gene expression variability across individuals, whereas gene expression variability was lower in less aggressive, mutated CLL.

The investigators validated these observations by comparing them against a second sample group consisting of 24 mutated and 36 unmutated CLL samples.

The results suggested that CLL aggressiveness is specifically determined by a set of 500 genes showing increased expression variability across individuals. The genes are involved in processes such as adaptation to the environment, cell death, tumor growth, and drug resistance.

“Our conclusion is that the coefficient of variation for gene expression in CLL efficiently predicts its aggressiveness,” said study author Alfonso Valencia, PhD, of Centro Nacional de Investigaciones Oncologicas (CNIO) in Madrid, Spain.

“More importantly, if further research confirms these findings, a classifier based on the measurement of gene expression variability could be created to predict the disease subtype of CLL patients.”

The researchers said their next step is to discover the mechanisms responsible for the high levels of expression variability for a given gene across individuals.

Understanding the mechanisms underlying this phenomenon is of crucial relevance for oncology research, the investigators said, as it is linked to tumor heterogeneity, a key feature of cancer progression and drug resistance.

The greater the genetic variability in a tumor, the better it will adapt to its environment, and the more probabilities for this tumor to spread, develop resistance to cancer therapies, and metastasize to distant organs.

CLL in the bone marrow

The genetic variability of chronic lymphocytic leukemia (CLL) appears to predict its aggressiveness, according to a study published in Genome Medicine.

Investigators found evidence suggesting that greater variability in gene expression is associated with more aggressive disease.

The team analyzed gene expression in two cohorts of CLL patients—those with IgVH mutations and a good prognosis and those with unmutated CLL who have more aggressive disease.

The researchers examined 70 mutated and 52 unmutated CLL samples, as well as 20 control samples taken from healthy individuals.

Unmutated, aggressive CLL showed increased gene expression variability across individuals, whereas gene expression variability was lower in less aggressive, mutated CLL.

The investigators validated these observations by comparing them against a second sample group consisting of 24 mutated and 36 unmutated CLL samples.

The results suggested that CLL aggressiveness is specifically determined by a set of 500 genes showing increased expression variability across individuals. The genes are involved in processes such as adaptation to the environment, cell death, tumor growth, and drug resistance.

“Our conclusion is that the coefficient of variation for gene expression in CLL efficiently predicts its aggressiveness,” said study author Alfonso Valencia, PhD, of Centro Nacional de Investigaciones Oncologicas (CNIO) in Madrid, Spain.

“More importantly, if further research confirms these findings, a classifier based on the measurement of gene expression variability could be created to predict the disease subtype of CLL patients.”

The researchers said their next step is to discover the mechanisms responsible for the high levels of expression variability for a given gene across individuals.

Understanding the mechanisms underlying this phenomenon is of crucial relevance for oncology research, the investigators said, as it is linked to tumor heterogeneity, a key feature of cancer progression and drug resistance.

The greater the genetic variability in a tumor, the better it will adapt to its environment, and the more probabilities for this tumor to spread, develop resistance to cancer therapies, and metastasize to distant organs.