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Studies reveal potential therapeutic targets for resistant AML
Image by NIGMS
A pair of studies suggest the DNA replication checkpoint pathway could be targeted to treat resistant acute myeloid leukemia (AML).
One study indicated that the kinase CHK1, which coordinates the DNA damage response and cell-cycle checkpoint response, might be targeted to overcome cytarabine resistance in AML.
The other study suggested that ATR, a kinase that activates CHK1, and ATM, a second upstream kinase in the DNA damage response, might be therapeutic targets in MLL-rearranged AML.
Both studies were published in Science Sigaling.
Laure David, of La Ligue Contre Le Cancer in Toulouse, France, and colleagues conducted this study.
The researchers integrated gene expression data with survival data from 198 AML patients who were previously treated with cytarabine-based chemotherapy.
The data showed that patients with high expression of CHEK1, the gene that encodes CHK1, had poor survival. And patient cells with high CHK1 abundance were resistant to cytarabine.
However, when the researchers exposed the cells with high CHK1 abundance to the CHK1 inhibitor SCH900776, they observed “reduced clonogenic ability and progression of DNA replication in the presence of cytarabine.”
The team therefore concluded that treatment with a CHK1 inhibitor might overcome resistance to cytarabine-based treatments in AML. They also said that monitoring CHEK1 expression in AML patients could potentially predict outcomes and reveal patients who might benefit from treatment with a CHK1 inhibitor.
The second study was conducted by Isabel Morgado-Palacin, of the Spanish National Cancer Research Center in Madrid, and colleagues.
The researchers investigated ATR, which is the primary sensor of DNA replication stress, and ATM, a kinase that senses DNA double-strand breaks, as possible therapeutic targets in MLL-rearranged AML.
The team found that inhibiting ATR induced chromosomal breakage and death in murine AML-MLL cells in vitro. And inhibiting ATR in vivo reduced the tumor burden and prevented tumors from growing.
The researchers also found that inhibiting ATM prolonged survival in the mouse model of AML-MLL, which suggests that both ATR and ATM might be therapeutic targets in MLL-rearranged AML. 
Image by NIGMS
A pair of studies suggest the DNA replication checkpoint pathway could be targeted to treat resistant acute myeloid leukemia (AML).
One study indicated that the kinase CHK1, which coordinates the DNA damage response and cell-cycle checkpoint response, might be targeted to overcome cytarabine resistance in AML.
The other study suggested that ATR, a kinase that activates CHK1, and ATM, a second upstream kinase in the DNA damage response, might be therapeutic targets in MLL-rearranged AML.
Both studies were published in Science Sigaling.
Laure David, of La Ligue Contre Le Cancer in Toulouse, France, and colleagues conducted this study.
The researchers integrated gene expression data with survival data from 198 AML patients who were previously treated with cytarabine-based chemotherapy.
The data showed that patients with high expression of CHEK1, the gene that encodes CHK1, had poor survival. And patient cells with high CHK1 abundance were resistant to cytarabine.
However, when the researchers exposed the cells with high CHK1 abundance to the CHK1 inhibitor SCH900776, they observed “reduced clonogenic ability and progression of DNA replication in the presence of cytarabine.”
The team therefore concluded that treatment with a CHK1 inhibitor might overcome resistance to cytarabine-based treatments in AML. They also said that monitoring CHEK1 expression in AML patients could potentially predict outcomes and reveal patients who might benefit from treatment with a CHK1 inhibitor.
The second study was conducted by Isabel Morgado-Palacin, of the Spanish National Cancer Research Center in Madrid, and colleagues.
The researchers investigated ATR, which is the primary sensor of DNA replication stress, and ATM, a kinase that senses DNA double-strand breaks, as possible therapeutic targets in MLL-rearranged AML.
The team found that inhibiting ATR induced chromosomal breakage and death in murine AML-MLL cells in vitro. And inhibiting ATR in vivo reduced the tumor burden and prevented tumors from growing.
The researchers also found that inhibiting ATM prolonged survival in the mouse model of AML-MLL, which suggests that both ATR and ATM might be therapeutic targets in MLL-rearranged AML.
Image by NIGMS
A pair of studies suggest the DNA replication checkpoint pathway could be targeted to treat resistant acute myeloid leukemia (AML).
One study indicated that the kinase CHK1, which coordinates the DNA damage response and cell-cycle checkpoint response, might be targeted to overcome cytarabine resistance in AML.
The other study suggested that ATR, a kinase that activates CHK1, and ATM, a second upstream kinase in the DNA damage response, might be therapeutic targets in MLL-rearranged AML.
Both studies were published in Science Sigaling.
Laure David, of La Ligue Contre Le Cancer in Toulouse, France, and colleagues conducted this study.
The researchers integrated gene expression data with survival data from 198 AML patients who were previously treated with cytarabine-based chemotherapy.
The data showed that patients with high expression of CHEK1, the gene that encodes CHK1, had poor survival. And patient cells with high CHK1 abundance were resistant to cytarabine.
However, when the researchers exposed the cells with high CHK1 abundance to the CHK1 inhibitor SCH900776, they observed “reduced clonogenic ability and progression of DNA replication in the presence of cytarabine.”
The team therefore concluded that treatment with a CHK1 inhibitor might overcome resistance to cytarabine-based treatments in AML. They also said that monitoring CHEK1 expression in AML patients could potentially predict outcomes and reveal patients who might benefit from treatment with a CHK1 inhibitor.
The second study was conducted by Isabel Morgado-Palacin, of the Spanish National Cancer Research Center in Madrid, and colleagues.
The researchers investigated ATR, which is the primary sensor of DNA replication stress, and ATM, a kinase that senses DNA double-strand breaks, as possible therapeutic targets in MLL-rearranged AML.
The team found that inhibiting ATR induced chromosomal breakage and death in murine AML-MLL cells in vitro. And inhibiting ATR in vivo reduced the tumor burden and prevented tumors from growing.
The researchers also found that inhibiting ATM prolonged survival in the mouse model of AML-MLL, which suggests that both ATR and ATM might be therapeutic targets in MLL-rearranged AML.
Effects of caring for advanced cancer patients
SAN FRANCISCO—Family caregivers of patients with high-mortality cancers may often experience high levels of depression and anxiety, results of a survey suggest.
The survey showed that caregivers can spend more than 8 hours a day providing care.
And as caregiving time increases, self-care behaviors such as sleep and exercise decline, which may confer poorer mental health.
These findings were presented at the 2016 Palliative Care in Oncology Symposium (abstract 239).
“Caregivers and patients are faced with an enormous physical and emotional toll when dealing with advanced cancer,” said study investigator J. Nicholas Dionne-Odom, PhD, RN, of the University of Alabama at Birmingham.
“When they put their own health and well-being on the back burner, it can affect their care to the patient.”
Dr Dionne-Odom and his colleagues conducted a cross-sectional survey of 294 family caregivers of Medicare beneficiaries diagnosed with pancreatic, lung, brain, ovarian, head and neck, hematologic, or stage IV cancers.
The survey was fielded across 8 cancer centers in Alabama, Florida, and Tennessee. Survey questions explored measures of self-care behaviors and quality of life.
The caregivers had an average age of 66. They were mostly female (72.8%), white (91.2%), retired (54.4%), and the patient’s spouse/partner (60.2%). Nearly half of the caregivers lived in rural areas (46.9%), and more than half had annual incomes less than $50,000 (53.8%).
Most of the caregivers said they provided care 6 to 7 days a week (71%) for more than 1 year (68%).
Twenty-three percent of caregivers reported a high level of depressive symptoms, and 34% reported borderline or high levels of anxiety symptoms, associated with significantly lower scores for self-care.
Lower self-care behavior scores were associated with a longer overall duration of caregiving, more hours in the day spent caregiving, more days of the week spent caregiving, and with fair or poor patient health.
“We hope our research rallies the oncology palliative care communities to develop assessment tools and services that support caregivers,” Dr Dionne-Odom said. “These efforts would help ensure that caregivers are supported and healthy when they take on the important role of caring for an individual with advanced cancer.”
SAN FRANCISCO—Family caregivers of patients with high-mortality cancers may often experience high levels of depression and anxiety, results of a survey suggest.
The survey showed that caregivers can spend more than 8 hours a day providing care.
And as caregiving time increases, self-care behaviors such as sleep and exercise decline, which may confer poorer mental health.
These findings were presented at the 2016 Palliative Care in Oncology Symposium (abstract 239).
“Caregivers and patients are faced with an enormous physical and emotional toll when dealing with advanced cancer,” said study investigator J. Nicholas Dionne-Odom, PhD, RN, of the University of Alabama at Birmingham.
“When they put their own health and well-being on the back burner, it can affect their care to the patient.”
Dr Dionne-Odom and his colleagues conducted a cross-sectional survey of 294 family caregivers of Medicare beneficiaries diagnosed with pancreatic, lung, brain, ovarian, head and neck, hematologic, or stage IV cancers.
The survey was fielded across 8 cancer centers in Alabama, Florida, and Tennessee. Survey questions explored measures of self-care behaviors and quality of life.
The caregivers had an average age of 66. They were mostly female (72.8%), white (91.2%), retired (54.4%), and the patient’s spouse/partner (60.2%). Nearly half of the caregivers lived in rural areas (46.9%), and more than half had annual incomes less than $50,000 (53.8%).
Most of the caregivers said they provided care 6 to 7 days a week (71%) for more than 1 year (68%).
Twenty-three percent of caregivers reported a high level of depressive symptoms, and 34% reported borderline or high levels of anxiety symptoms, associated with significantly lower scores for self-care.
Lower self-care behavior scores were associated with a longer overall duration of caregiving, more hours in the day spent caregiving, more days of the week spent caregiving, and with fair or poor patient health.
“We hope our research rallies the oncology palliative care communities to develop assessment tools and services that support caregivers,” Dr Dionne-Odom said. “These efforts would help ensure that caregivers are supported and healthy when they take on the important role of caring for an individual with advanced cancer.”
SAN FRANCISCO—Family caregivers of patients with high-mortality cancers may often experience high levels of depression and anxiety, results of a survey suggest.
The survey showed that caregivers can spend more than 8 hours a day providing care.
And as caregiving time increases, self-care behaviors such as sleep and exercise decline, which may confer poorer mental health.
These findings were presented at the 2016 Palliative Care in Oncology Symposium (abstract 239).
“Caregivers and patients are faced with an enormous physical and emotional toll when dealing with advanced cancer,” said study investigator J. Nicholas Dionne-Odom, PhD, RN, of the University of Alabama at Birmingham.
“When they put their own health and well-being on the back burner, it can affect their care to the patient.”
Dr Dionne-Odom and his colleagues conducted a cross-sectional survey of 294 family caregivers of Medicare beneficiaries diagnosed with pancreatic, lung, brain, ovarian, head and neck, hematologic, or stage IV cancers.
The survey was fielded across 8 cancer centers in Alabama, Florida, and Tennessee. Survey questions explored measures of self-care behaviors and quality of life.
The caregivers had an average age of 66. They were mostly female (72.8%), white (91.2%), retired (54.4%), and the patient’s spouse/partner (60.2%). Nearly half of the caregivers lived in rural areas (46.9%), and more than half had annual incomes less than $50,000 (53.8%).
Most of the caregivers said they provided care 6 to 7 days a week (71%) for more than 1 year (68%).
Twenty-three percent of caregivers reported a high level of depressive symptoms, and 34% reported borderline or high levels of anxiety symptoms, associated with significantly lower scores for self-care.
Lower self-care behavior scores were associated with a longer overall duration of caregiving, more hours in the day spent caregiving, more days of the week spent caregiving, and with fair or poor patient health.
“We hope our research rallies the oncology palliative care communities to develop assessment tools and services that support caregivers,” Dr Dionne-Odom said. “These efforts would help ensure that caregivers are supported and healthy when they take on the important role of caring for an individual with advanced cancer.”
Study reveals barriers to accessing palliative care services
©ASCO/Todd Buchanan 2016
SAN FRANCISCO—Patients may face challenges when trying to access palliative and supportive care services at cancer centers, a new study suggests.
Researchers took a “mystery shopper” approach and placed calls to cancer centers inquiring about palliative and supportive care services for a family member.
The callers sometimes had difficulty obtaining information about these services, even though all of the centers offer them.
“It’s sobering to hear that such services are not readily accessible at many centers,” said study investigator Kathryn Hutchins, a medical student at Duke University in Durham, North Carolina.
“However, it provides an opportunity for cancer centers to empower their front-line staff, as well as the oncology care team, through education and training so that the entire enterprise has a common understanding of palliative care and how to access it.”
Hutchins and her colleagues presented this research at the 2016 Palliative Care in Oncology Symposium (abstract 122).
The researchers placed 160 calls to 40 major cancer centers. The team chose to focus on National Cancer Institute-designated cancer centers because they all provide palliative care services along with other supportive care services.
The researchers used the same script for every call, asking about services for a 58-year-old female who was recently diagnosed with inoperable liver cancer. The team called each center 4 times on different days.
In 38.2% of the calls, the researchers were not able to receive complete information about supportive care services.
In 9.5% of calls, cancer center staff gave an answer other than “yes” regarding the availability of palliative care services, even though such services were available.
The answers varied and included responses such as:
- Palliative care was for end-of-life patients only (n=2)
- No physicians specialized in symptom management (n=3)
- A medical record review would be needed first (n=2).
In addition, 10 staff members said they were unsure about the availability of palliative care, and 2 were unfamiliar with the term.
Overall, 37.6% of the callers were told that all 7 supportive care services they inquired about were offered.
“As oncologists, we like to believe that, when we refer patients to our institution’s helpline, they will get connected to the services they need, but that doesn’t always happen,” said study investigator Arif Kamal, MD, of Duke Cancer Institute.
“It’s important for oncologists to be aware of these barriers and to work to eliminate them.”
©ASCO/Todd Buchanan 2016
SAN FRANCISCO—Patients may face challenges when trying to access palliative and supportive care services at cancer centers, a new study suggests.
Researchers took a “mystery shopper” approach and placed calls to cancer centers inquiring about palliative and supportive care services for a family member.
The callers sometimes had difficulty obtaining information about these services, even though all of the centers offer them.
“It’s sobering to hear that such services are not readily accessible at many centers,” said study investigator Kathryn Hutchins, a medical student at Duke University in Durham, North Carolina.
“However, it provides an opportunity for cancer centers to empower their front-line staff, as well as the oncology care team, through education and training so that the entire enterprise has a common understanding of palliative care and how to access it.”
Hutchins and her colleagues presented this research at the 2016 Palliative Care in Oncology Symposium (abstract 122).
The researchers placed 160 calls to 40 major cancer centers. The team chose to focus on National Cancer Institute-designated cancer centers because they all provide palliative care services along with other supportive care services.
The researchers used the same script for every call, asking about services for a 58-year-old female who was recently diagnosed with inoperable liver cancer. The team called each center 4 times on different days.
In 38.2% of the calls, the researchers were not able to receive complete information about supportive care services.
In 9.5% of calls, cancer center staff gave an answer other than “yes” regarding the availability of palliative care services, even though such services were available.
The answers varied and included responses such as:
- Palliative care was for end-of-life patients only (n=2)
- No physicians specialized in symptom management (n=3)
- A medical record review would be needed first (n=2).
In addition, 10 staff members said they were unsure about the availability of palliative care, and 2 were unfamiliar with the term.
Overall, 37.6% of the callers were told that all 7 supportive care services they inquired about were offered.
“As oncologists, we like to believe that, when we refer patients to our institution’s helpline, they will get connected to the services they need, but that doesn’t always happen,” said study investigator Arif Kamal, MD, of Duke Cancer Institute.
“It’s important for oncologists to be aware of these barriers and to work to eliminate them.”
©ASCO/Todd Buchanan 2016
SAN FRANCISCO—Patients may face challenges when trying to access palliative and supportive care services at cancer centers, a new study suggests.
Researchers took a “mystery shopper” approach and placed calls to cancer centers inquiring about palliative and supportive care services for a family member.
The callers sometimes had difficulty obtaining information about these services, even though all of the centers offer them.
“It’s sobering to hear that such services are not readily accessible at many centers,” said study investigator Kathryn Hutchins, a medical student at Duke University in Durham, North Carolina.
“However, it provides an opportunity for cancer centers to empower their front-line staff, as well as the oncology care team, through education and training so that the entire enterprise has a common understanding of palliative care and how to access it.”
Hutchins and her colleagues presented this research at the 2016 Palliative Care in Oncology Symposium (abstract 122).
The researchers placed 160 calls to 40 major cancer centers. The team chose to focus on National Cancer Institute-designated cancer centers because they all provide palliative care services along with other supportive care services.
The researchers used the same script for every call, asking about services for a 58-year-old female who was recently diagnosed with inoperable liver cancer. The team called each center 4 times on different days.
In 38.2% of the calls, the researchers were not able to receive complete information about supportive care services.
In 9.5% of calls, cancer center staff gave an answer other than “yes” regarding the availability of palliative care services, even though such services were available.
The answers varied and included responses such as:
- Palliative care was for end-of-life patients only (n=2)
- No physicians specialized in symptom management (n=3)
- A medical record review would be needed first (n=2).
In addition, 10 staff members said they were unsure about the availability of palliative care, and 2 were unfamiliar with the term.
Overall, 37.6% of the callers were told that all 7 supportive care services they inquired about were offered.
“As oncologists, we like to believe that, when we refer patients to our institution’s helpline, they will get connected to the services they need, but that doesn’t always happen,” said study investigator Arif Kamal, MD, of Duke Cancer Institute.
“It’s important for oncologists to be aware of these barriers and to work to eliminate them.”
Pregnancy screening lacking in girls with AML, ALL
patient and her father
Photo by Rhoda Baer
Many adolescent females are not being screened for pregnancy before beginning chemotherapy or undergoing computed tomography (CT) scans, according to research published in Cancer.
In this study, pregnancy screening was underused in adolescents with acute lymphoblastic leukemia (ALL), those with acute myeloid leukemia (AML), and those who received CT scans of the abdomen or pelvis during visits to the emergency room (ER).
“We found that adolescent girls are not adequately screened for pregnancy prior to receiving chemotherapy or CT scans that could harm a developing fetus,” said study author Pooja Rao, MD, of Penn State Health’s Milton S. Hershey Medical Center in Hershey, Pennsylvania.
“Adolescents with ALL, the most common childhood cancer, had the lowest rates of pregnancy screening of the patients we studied.”
Dr Rao and her colleagues examined pregnancy screening patterns among adolescent females newly diagnosed with ALL or AML, as well as adolescent females who visited the ER and received CT scans of the abdomen or pelvis. (In emergency medicine, pregnancy screening protocols exist for adolescents prior to receiving radiation due to the known teratogenic risks of radiation.)
The analysis included patients ages 10 to 18 who were admitted to hospitals across the US from 1999 to 2011. There were a total of 35,650 patient visits—127 for AML patients, 889 for ALL patients, and 34,634 ER admissions with CT scans of the abdomen/pelvis.
The proportion of visits with an appropriately timed pregnancy test was 35% for the ALL patients, 64% for the AML patients, and 58% in the ER group.
The researchers noted that ALL patients tended to be younger than the AML patients and the ER patients, and there was substantial variation in pregnancy screening patterns among the different hospitals.
However, in a generalized estimating equation (GEE) model adjusted for hospital clustering and patient age, patients with ALL were significantly less likely to have an appropriately timed pregnancy test when compared to patients in the ER cohort. The adjusted prevalence ratio was 0.71 (95% CI, 0.65-0.78).
And in a GEE model adjusted for hospital clustering, patients with AML were more likely to have an appropriately timed pregnancy test than patients in the ER cohort, but this difference was not statistically significant. The adjusted prevalence ratio was 1.12 (95% CI, 0.99-1.27).
The researchers also found that pregnancy screening continued to increase over time in the ALL cohort but remained “relatively stable” from 2008 onward in the AML and ER cohorts.
“Since nearly all chemotherapy agents used for childhood/adolescent acute leukemia can cause potential harm to a developing fetus, our findings indicate a need for standardized pregnancy screening practices for adolescent patients being treated for cancer,” Dr Rao said.
She also noted that the low rates of pregnancy screening observed in this study may indicate a reluctance on the part of pediatric oncologists to discuss sexual health practices with adolescent patients.
“While sexual health discussions and education may traditionally be thought to be the responsibility of the patient’s primary care provider, adolescents with cancer will often see their oncologist frequently over the course of their cancer treatment and afterwards,” Dr Rao said. “Oncologists therefore are well-positioned to initiate discussions about sexual health with their patients.”
patient and her father
Photo by Rhoda Baer
Many adolescent females are not being screened for pregnancy before beginning chemotherapy or undergoing computed tomography (CT) scans, according to research published in Cancer.
In this study, pregnancy screening was underused in adolescents with acute lymphoblastic leukemia (ALL), those with acute myeloid leukemia (AML), and those who received CT scans of the abdomen or pelvis during visits to the emergency room (ER).
“We found that adolescent girls are not adequately screened for pregnancy prior to receiving chemotherapy or CT scans that could harm a developing fetus,” said study author Pooja Rao, MD, of Penn State Health’s Milton S. Hershey Medical Center in Hershey, Pennsylvania.
“Adolescents with ALL, the most common childhood cancer, had the lowest rates of pregnancy screening of the patients we studied.”
Dr Rao and her colleagues examined pregnancy screening patterns among adolescent females newly diagnosed with ALL or AML, as well as adolescent females who visited the ER and received CT scans of the abdomen or pelvis. (In emergency medicine, pregnancy screening protocols exist for adolescents prior to receiving radiation due to the known teratogenic risks of radiation.)
The analysis included patients ages 10 to 18 who were admitted to hospitals across the US from 1999 to 2011. There were a total of 35,650 patient visits—127 for AML patients, 889 for ALL patients, and 34,634 ER admissions with CT scans of the abdomen/pelvis.
The proportion of visits with an appropriately timed pregnancy test was 35% for the ALL patients, 64% for the AML patients, and 58% in the ER group.
The researchers noted that ALL patients tended to be younger than the AML patients and the ER patients, and there was substantial variation in pregnancy screening patterns among the different hospitals.
However, in a generalized estimating equation (GEE) model adjusted for hospital clustering and patient age, patients with ALL were significantly less likely to have an appropriately timed pregnancy test when compared to patients in the ER cohort. The adjusted prevalence ratio was 0.71 (95% CI, 0.65-0.78).
And in a GEE model adjusted for hospital clustering, patients with AML were more likely to have an appropriately timed pregnancy test than patients in the ER cohort, but this difference was not statistically significant. The adjusted prevalence ratio was 1.12 (95% CI, 0.99-1.27).
The researchers also found that pregnancy screening continued to increase over time in the ALL cohort but remained “relatively stable” from 2008 onward in the AML and ER cohorts.
“Since nearly all chemotherapy agents used for childhood/adolescent acute leukemia can cause potential harm to a developing fetus, our findings indicate a need for standardized pregnancy screening practices for adolescent patients being treated for cancer,” Dr Rao said.
She also noted that the low rates of pregnancy screening observed in this study may indicate a reluctance on the part of pediatric oncologists to discuss sexual health practices with adolescent patients.
“While sexual health discussions and education may traditionally be thought to be the responsibility of the patient’s primary care provider, adolescents with cancer will often see their oncologist frequently over the course of their cancer treatment and afterwards,” Dr Rao said. “Oncologists therefore are well-positioned to initiate discussions about sexual health with their patients.”
patient and her father
Photo by Rhoda Baer
Many adolescent females are not being screened for pregnancy before beginning chemotherapy or undergoing computed tomography (CT) scans, according to research published in Cancer.
In this study, pregnancy screening was underused in adolescents with acute lymphoblastic leukemia (ALL), those with acute myeloid leukemia (AML), and those who received CT scans of the abdomen or pelvis during visits to the emergency room (ER).
“We found that adolescent girls are not adequately screened for pregnancy prior to receiving chemotherapy or CT scans that could harm a developing fetus,” said study author Pooja Rao, MD, of Penn State Health’s Milton S. Hershey Medical Center in Hershey, Pennsylvania.
“Adolescents with ALL, the most common childhood cancer, had the lowest rates of pregnancy screening of the patients we studied.”
Dr Rao and her colleagues examined pregnancy screening patterns among adolescent females newly diagnosed with ALL or AML, as well as adolescent females who visited the ER and received CT scans of the abdomen or pelvis. (In emergency medicine, pregnancy screening protocols exist for adolescents prior to receiving radiation due to the known teratogenic risks of radiation.)
The analysis included patients ages 10 to 18 who were admitted to hospitals across the US from 1999 to 2011. There were a total of 35,650 patient visits—127 for AML patients, 889 for ALL patients, and 34,634 ER admissions with CT scans of the abdomen/pelvis.
The proportion of visits with an appropriately timed pregnancy test was 35% for the ALL patients, 64% for the AML patients, and 58% in the ER group.
The researchers noted that ALL patients tended to be younger than the AML patients and the ER patients, and there was substantial variation in pregnancy screening patterns among the different hospitals.
However, in a generalized estimating equation (GEE) model adjusted for hospital clustering and patient age, patients with ALL were significantly less likely to have an appropriately timed pregnancy test when compared to patients in the ER cohort. The adjusted prevalence ratio was 0.71 (95% CI, 0.65-0.78).
And in a GEE model adjusted for hospital clustering, patients with AML were more likely to have an appropriately timed pregnancy test than patients in the ER cohort, but this difference was not statistically significant. The adjusted prevalence ratio was 1.12 (95% CI, 0.99-1.27).
The researchers also found that pregnancy screening continued to increase over time in the ALL cohort but remained “relatively stable” from 2008 onward in the AML and ER cohorts.
“Since nearly all chemotherapy agents used for childhood/adolescent acute leukemia can cause potential harm to a developing fetus, our findings indicate a need for standardized pregnancy screening practices for adolescent patients being treated for cancer,” Dr Rao said.
She also noted that the low rates of pregnancy screening observed in this study may indicate a reluctance on the part of pediatric oncologists to discuss sexual health practices with adolescent patients.
“While sexual health discussions and education may traditionally be thought to be the responsibility of the patient’s primary care provider, adolescents with cancer will often see their oncologist frequently over the course of their cancer treatment and afterwards,” Dr Rao said. “Oncologists therefore are well-positioned to initiate discussions about sexual health with their patients.”
Cancer patients’ caregivers may carry greater burden
©ASCO/Todd Buchanan 2016
SAN FRANCISCO—New research suggests caring for a loved one with cancer may be more burdensome than caring for a loved one with a different condition.
Researchers analyzed data from “Caregiving in the U.S. 2015,” an online panel study of unpaid adult caregivers.
The team compared cancer and non-cancer caregivers to determine similarities and differences in characteristics and experiences.
The findings were presented at the 2016 Palliative Care in Oncology Symposium (abstract 4).
The study included 1248 caregivers, age 18 and older at the time they were surveyed, who provided care to an adult patient. Seven percent of these caregivers were looking after patients with cancer.
Cancer caregivers reported spending more hours per week providing care than non-cancer caregivers—32.9 and 23.9 hours, respectively.
In addition, cancer caregivers were more likely than other caregivers to communicate with healthcare professionals (82% and 62%, respectively), monitor and adjust patients’ care (76% and 66%, respectively), and advocate on behalf of patients (62% and 49%, respectively).
Despite high levels of engagement with providers, cancer caregivers were nearly twice as likely as non-cancer caregivers to report needing more help and information with making end-of-life decisions—40% and 21%, respectively.
“Our research demonstrates the ripple effect that cancer has on families and patient support systems,” said study investigator Erin Kent, PhD, of the National Cancer Institute in Rockville, Maryland.
“Caregiving can be extremely stressful and demanding—physically, emotionally, and financially. The data show we need to do a better job of supporting these individuals, as their wellbeing is essential to the patient’s quality of life and outcomes.”
Dr Kent emphasized the cyclical nature of cancer care, often requiring short, highly intense periods of time where patients undergo active treatment as a possible reason for the increased intensity in caregiving. She noted that such intensity is also associated with increased caregiver stress and depression.
“Based on our findings, it’s clear we need additional research on caregiving to better understand at what point providers and clinicians should intervene to assess the wellbeing of caregivers,” Dr Kent said.
“Technology, combined with use of a clinical distress rating system, could be promising in the future as a means to ensure caregivers are being supported in a meaningful way.”
©ASCO/Todd Buchanan 2016
SAN FRANCISCO—New research suggests caring for a loved one with cancer may be more burdensome than caring for a loved one with a different condition.
Researchers analyzed data from “Caregiving in the U.S. 2015,” an online panel study of unpaid adult caregivers.
The team compared cancer and non-cancer caregivers to determine similarities and differences in characteristics and experiences.
The findings were presented at the 2016 Palliative Care in Oncology Symposium (abstract 4).
The study included 1248 caregivers, age 18 and older at the time they were surveyed, who provided care to an adult patient. Seven percent of these caregivers were looking after patients with cancer.
Cancer caregivers reported spending more hours per week providing care than non-cancer caregivers—32.9 and 23.9 hours, respectively.
In addition, cancer caregivers were more likely than other caregivers to communicate with healthcare professionals (82% and 62%, respectively), monitor and adjust patients’ care (76% and 66%, respectively), and advocate on behalf of patients (62% and 49%, respectively).
Despite high levels of engagement with providers, cancer caregivers were nearly twice as likely as non-cancer caregivers to report needing more help and information with making end-of-life decisions—40% and 21%, respectively.
“Our research demonstrates the ripple effect that cancer has on families and patient support systems,” said study investigator Erin Kent, PhD, of the National Cancer Institute in Rockville, Maryland.
“Caregiving can be extremely stressful and demanding—physically, emotionally, and financially. The data show we need to do a better job of supporting these individuals, as their wellbeing is essential to the patient’s quality of life and outcomes.”
Dr Kent emphasized the cyclical nature of cancer care, often requiring short, highly intense periods of time where patients undergo active treatment as a possible reason for the increased intensity in caregiving. She noted that such intensity is also associated with increased caregiver stress and depression.
“Based on our findings, it’s clear we need additional research on caregiving to better understand at what point providers and clinicians should intervene to assess the wellbeing of caregivers,” Dr Kent said.
“Technology, combined with use of a clinical distress rating system, could be promising in the future as a means to ensure caregivers are being supported in a meaningful way.”
©ASCO/Todd Buchanan 2016
SAN FRANCISCO—New research suggests caring for a loved one with cancer may be more burdensome than caring for a loved one with a different condition.
Researchers analyzed data from “Caregiving in the U.S. 2015,” an online panel study of unpaid adult caregivers.
The team compared cancer and non-cancer caregivers to determine similarities and differences in characteristics and experiences.
The findings were presented at the 2016 Palliative Care in Oncology Symposium (abstract 4).
The study included 1248 caregivers, age 18 and older at the time they were surveyed, who provided care to an adult patient. Seven percent of these caregivers were looking after patients with cancer.
Cancer caregivers reported spending more hours per week providing care than non-cancer caregivers—32.9 and 23.9 hours, respectively.
In addition, cancer caregivers were more likely than other caregivers to communicate with healthcare professionals (82% and 62%, respectively), monitor and adjust patients’ care (76% and 66%, respectively), and advocate on behalf of patients (62% and 49%, respectively).
Despite high levels of engagement with providers, cancer caregivers were nearly twice as likely as non-cancer caregivers to report needing more help and information with making end-of-life decisions—40% and 21%, respectively.
“Our research demonstrates the ripple effect that cancer has on families and patient support systems,” said study investigator Erin Kent, PhD, of the National Cancer Institute in Rockville, Maryland.
“Caregiving can be extremely stressful and demanding—physically, emotionally, and financially. The data show we need to do a better job of supporting these individuals, as their wellbeing is essential to the patient’s quality of life and outcomes.”
Dr Kent emphasized the cyclical nature of cancer care, often requiring short, highly intense periods of time where patients undergo active treatment as a possible reason for the increased intensity in caregiving. She noted that such intensity is also associated with increased caregiver stress and depression.
“Based on our findings, it’s clear we need additional research on caregiving to better understand at what point providers and clinicians should intervene to assess the wellbeing of caregivers,” Dr Kent said.
“Technology, combined with use of a clinical distress rating system, could be promising in the future as a means to ensure caregivers are being supported in a meaningful way.”
Improving communication between cancer pts and docs
©ASCO/Todd Buchanan 2016
SAN FRANCISCO—Results of the VOICE study showed that training advanced cancer patients and their oncologists on how to communicate resulted in more clinically meaningful discussions between the parties.
However, these discussions did not significantly improve patients’ understanding of their prognosis, have a significant impact on their quality of life or end-of-life care, or significantly improve the
patient-physician relationship.
Ronald Epstein, MD, of the University of Rochester in New York, and his colleagues reported results from this study in JAMA Oncology and at the 2016 Palliative Care in Oncology Symposium (abstract 2).
The VOICE study included 265 patients with stage 3 or 4 cancer, 130 of whom received communication training. As part of the training, patients received a booklet Dr Epstein’s team wrote called “My Cancer Care: What Now? What Next? What I Prefer.”
The patients and their caregivers also met with social workers or nurses to discuss commonly asked questions and how to express their fears, for example, or how to be assertive and state their preferences.
Of the 38 oncologists studied, 19 received communication training. This included mock office sessions with actors (known as standardized patients), video training, and individualized feedback.
Later, the researchers audio-recorded real sessions between the oncologists and patients, then asked both groups to fill out questionnaires. The team coded the interactions and matched the scores to the goals of the training.
Results
The study’s primary endpoint was a composite of 4 communication measures—engaging patients in consultations, responding to emotions, informing patients about prognosis and treatment choices, and balanced framing of information.
The researchers found that communication training resulted in a significant improvement in this endpoint (P=0.02).
“We have shown, in the first large study of its kind, that it is possible to change the conversation in advanced cancer,” Dr Epstein said. “This is a huge first step.”
However, when Dr Epstein and his colleagues looked at the individual components of the endpoint, only the engaging measure was significantly different between the intervention and control groups.
Communication training had no significant effect on the patient-physician relationship, patients’ quality of life, or healthcare utilization at the end of life.
Likewise, communication training had no significant effect on patients’ understanding of their prognosis, which was assessed by the discordance in 2-year survival estimates and curability estimates between patients and physicians.
“We need to try harder to communicate well so that it’s harder to miscommunicate,” Dr Epstein said. “Simply having the conversation is not enough. The quality of the conversation will influence a mutual understanding between patients and their oncologists.”
The researchers said a limitation of this study may have been the timing of the training, which was only provided once and not timed to key decision points during patients’ trajectories. The effects of the training may have waned over the months, especially as the cancer progressed.
“We need to embed communication interventions into the fabric of everyday clinical care,” Dr Epstein said. “This does not take a lot of time, but, in our audio-recordings, there was precious little dialogue that reaffirmed the human experience and the needs of patients. The next step is to make good communication the rule, not the exception, so that cancer patients’ voices can be heard.”
©ASCO/Todd Buchanan 2016
SAN FRANCISCO—Results of the VOICE study showed that training advanced cancer patients and their oncologists on how to communicate resulted in more clinically meaningful discussions between the parties.
However, these discussions did not significantly improve patients’ understanding of their prognosis, have a significant impact on their quality of life or end-of-life care, or significantly improve the
patient-physician relationship.
Ronald Epstein, MD, of the University of Rochester in New York, and his colleagues reported results from this study in JAMA Oncology and at the 2016 Palliative Care in Oncology Symposium (abstract 2).
The VOICE study included 265 patients with stage 3 or 4 cancer, 130 of whom received communication training. As part of the training, patients received a booklet Dr Epstein’s team wrote called “My Cancer Care: What Now? What Next? What I Prefer.”
The patients and their caregivers also met with social workers or nurses to discuss commonly asked questions and how to express their fears, for example, or how to be assertive and state their preferences.
Of the 38 oncologists studied, 19 received communication training. This included mock office sessions with actors (known as standardized patients), video training, and individualized feedback.
Later, the researchers audio-recorded real sessions between the oncologists and patients, then asked both groups to fill out questionnaires. The team coded the interactions and matched the scores to the goals of the training.
Results
The study’s primary endpoint was a composite of 4 communication measures—engaging patients in consultations, responding to emotions, informing patients about prognosis and treatment choices, and balanced framing of information.
The researchers found that communication training resulted in a significant improvement in this endpoint (P=0.02).
“We have shown, in the first large study of its kind, that it is possible to change the conversation in advanced cancer,” Dr Epstein said. “This is a huge first step.”
However, when Dr Epstein and his colleagues looked at the individual components of the endpoint, only the engaging measure was significantly different between the intervention and control groups.
Communication training had no significant effect on the patient-physician relationship, patients’ quality of life, or healthcare utilization at the end of life.
Likewise, communication training had no significant effect on patients’ understanding of their prognosis, which was assessed by the discordance in 2-year survival estimates and curability estimates between patients and physicians.
“We need to try harder to communicate well so that it’s harder to miscommunicate,” Dr Epstein said. “Simply having the conversation is not enough. The quality of the conversation will influence a mutual understanding between patients and their oncologists.”
The researchers said a limitation of this study may have been the timing of the training, which was only provided once and not timed to key decision points during patients’ trajectories. The effects of the training may have waned over the months, especially as the cancer progressed.
“We need to embed communication interventions into the fabric of everyday clinical care,” Dr Epstein said. “This does not take a lot of time, but, in our audio-recordings, there was precious little dialogue that reaffirmed the human experience and the needs of patients. The next step is to make good communication the rule, not the exception, so that cancer patients’ voices can be heard.”
©ASCO/Todd Buchanan 2016
SAN FRANCISCO—Results of the VOICE study showed that training advanced cancer patients and their oncologists on how to communicate resulted in more clinically meaningful discussions between the parties.
However, these discussions did not significantly improve patients’ understanding of their prognosis, have a significant impact on their quality of life or end-of-life care, or significantly improve the
patient-physician relationship.
Ronald Epstein, MD, of the University of Rochester in New York, and his colleagues reported results from this study in JAMA Oncology and at the 2016 Palliative Care in Oncology Symposium (abstract 2).
The VOICE study included 265 patients with stage 3 or 4 cancer, 130 of whom received communication training. As part of the training, patients received a booklet Dr Epstein’s team wrote called “My Cancer Care: What Now? What Next? What I Prefer.”
The patients and their caregivers also met with social workers or nurses to discuss commonly asked questions and how to express their fears, for example, or how to be assertive and state their preferences.
Of the 38 oncologists studied, 19 received communication training. This included mock office sessions with actors (known as standardized patients), video training, and individualized feedback.
Later, the researchers audio-recorded real sessions between the oncologists and patients, then asked both groups to fill out questionnaires. The team coded the interactions and matched the scores to the goals of the training.
Results
The study’s primary endpoint was a composite of 4 communication measures—engaging patients in consultations, responding to emotions, informing patients about prognosis and treatment choices, and balanced framing of information.
The researchers found that communication training resulted in a significant improvement in this endpoint (P=0.02).
“We have shown, in the first large study of its kind, that it is possible to change the conversation in advanced cancer,” Dr Epstein said. “This is a huge first step.”
However, when Dr Epstein and his colleagues looked at the individual components of the endpoint, only the engaging measure was significantly different between the intervention and control groups.
Communication training had no significant effect on the patient-physician relationship, patients’ quality of life, or healthcare utilization at the end of life.
Likewise, communication training had no significant effect on patients’ understanding of their prognosis, which was assessed by the discordance in 2-year survival estimates and curability estimates between patients and physicians.
“We need to try harder to communicate well so that it’s harder to miscommunicate,” Dr Epstein said. “Simply having the conversation is not enough. The quality of the conversation will influence a mutual understanding between patients and their oncologists.”
The researchers said a limitation of this study may have been the timing of the training, which was only provided once and not timed to key decision points during patients’ trajectories. The effects of the training may have waned over the months, especially as the cancer progressed.
“We need to embed communication interventions into the fabric of everyday clinical care,” Dr Epstein said. “This does not take a lot of time, but, in our audio-recordings, there was precious little dialogue that reaffirmed the human experience and the needs of patients. The next step is to make good communication the rule, not the exception, so that cancer patients’ voices can be heard.”
Combo could provide cure for CML, team says
Preclinical research suggests that combining a BCL2 inhibitor with a BCR-ABL tyrosine kinase inhibitor (TKI) can eradicate leukemia stem cells (LSCs) in chronic myeloid leukemia (CML).
In mouse models of CML, combining the TKI nilotinib with the BCL2 inhibitor venetoclax enhanced antileukemic activity and decreased numbers of long-term LSCs.
The 2-drug combination exhibited similar activity in samples from patients with blast crisis CML.
“Our results demonstrate that . . . employing combined blockade of BCL-2 and BCR-ABL has the potential for curing CML and significantly improving outcomes for patients with blast crisis, and, as such, warrants clinical testing,” said Michael Andreeff, MD, of the University of Texas MD Anderson Cancer Center in Houston.
Dr Andreeff and his colleagues reported these results in Science Translational Medicine. The study was funded by National Institutes of Health, the Paul and Mary Haas Chair in Genetics, and Abbvie Inc., the company developing venetoclax.
The researchers noted that, although BCR-ABL TKIs have proven effective against CML, they rarely eliminate CML stem cells.
“It is believed that TKIs do not eliminate residual stem cells because they are not dependent on BCR-ABL signaling,” said study author Bing Carter, PhD, also of MD Anderson Cancer Center. “Hence, cures of CML with TKIs are rare.”
Dr Carter has worked for several years on eliminating residual CML stem cells, which could mean CML patients would no longer require long-term treatment with TKIs. Based on the current study, she and her colleagues believe that combining a TKI with a BCL-2 inhibitor may be a solution.
The researchers found that targeting both BCL-2 and BCR-ABL with venetoclax and nilotinib, respectively, exerted “potent antileukemic activity” and prolonged survival in BCR-ABL transgenic mice.
After stopping treatment, the median survival was 34.5 days for control mice, 70 days for mice treated with nilotinib alone (P=0.2146), 115 days for mice treated with venetoclax alone (P=0.0079), and 168 days for mice treated with nilotinib and venetoclax in combination (P=0.0002).
Subsequent experiments in mice showed that nilotinib alone did not significantly affect the frequency of long-term LSCs, although venetoclax alone did. Treatment with both drugs reduced the frequency of long-term LSCs even more than venetoclax alone.
Finally, the researchers tested venetoclax, nilotinib, and the combination in cells from 6 patients with blast crisis CML, all of whom had failed treatment with at least 1 TKI.
The team found that venetoclax and nilotinib had a synergistic apoptotic effect on bulk and stem/progenitor CML cells.
The researchers said these results suggest that combined inhibition of BCL-2 and BCR-ABL tyrosine kinase has the potential to significantly improve the depth of response and cure rates of chronic phase and blast crisis CML.
“This combination strategy may also apply to other malignancies that depend on kinase signaling for progression and maintenance,” Dr Andreeff added.
Preclinical research suggests that combining a BCL2 inhibitor with a BCR-ABL tyrosine kinase inhibitor (TKI) can eradicate leukemia stem cells (LSCs) in chronic myeloid leukemia (CML).
In mouse models of CML, combining the TKI nilotinib with the BCL2 inhibitor venetoclax enhanced antileukemic activity and decreased numbers of long-term LSCs.
The 2-drug combination exhibited similar activity in samples from patients with blast crisis CML.
“Our results demonstrate that . . . employing combined blockade of BCL-2 and BCR-ABL has the potential for curing CML and significantly improving outcomes for patients with blast crisis, and, as such, warrants clinical testing,” said Michael Andreeff, MD, of the University of Texas MD Anderson Cancer Center in Houston.
Dr Andreeff and his colleagues reported these results in Science Translational Medicine. The study was funded by National Institutes of Health, the Paul and Mary Haas Chair in Genetics, and Abbvie Inc., the company developing venetoclax.
The researchers noted that, although BCR-ABL TKIs have proven effective against CML, they rarely eliminate CML stem cells.
“It is believed that TKIs do not eliminate residual stem cells because they are not dependent on BCR-ABL signaling,” said study author Bing Carter, PhD, also of MD Anderson Cancer Center. “Hence, cures of CML with TKIs are rare.”
Dr Carter has worked for several years on eliminating residual CML stem cells, which could mean CML patients would no longer require long-term treatment with TKIs. Based on the current study, she and her colleagues believe that combining a TKI with a BCL-2 inhibitor may be a solution.
The researchers found that targeting both BCL-2 and BCR-ABL with venetoclax and nilotinib, respectively, exerted “potent antileukemic activity” and prolonged survival in BCR-ABL transgenic mice.
After stopping treatment, the median survival was 34.5 days for control mice, 70 days for mice treated with nilotinib alone (P=0.2146), 115 days for mice treated with venetoclax alone (P=0.0079), and 168 days for mice treated with nilotinib and venetoclax in combination (P=0.0002).
Subsequent experiments in mice showed that nilotinib alone did not significantly affect the frequency of long-term LSCs, although venetoclax alone did. Treatment with both drugs reduced the frequency of long-term LSCs even more than venetoclax alone.
Finally, the researchers tested venetoclax, nilotinib, and the combination in cells from 6 patients with blast crisis CML, all of whom had failed treatment with at least 1 TKI.
The team found that venetoclax and nilotinib had a synergistic apoptotic effect on bulk and stem/progenitor CML cells.
The researchers said these results suggest that combined inhibition of BCL-2 and BCR-ABL tyrosine kinase has the potential to significantly improve the depth of response and cure rates of chronic phase and blast crisis CML.
“This combination strategy may also apply to other malignancies that depend on kinase signaling for progression and maintenance,” Dr Andreeff added.
Preclinical research suggests that combining a BCL2 inhibitor with a BCR-ABL tyrosine kinase inhibitor (TKI) can eradicate leukemia stem cells (LSCs) in chronic myeloid leukemia (CML).
In mouse models of CML, combining the TKI nilotinib with the BCL2 inhibitor venetoclax enhanced antileukemic activity and decreased numbers of long-term LSCs.
The 2-drug combination exhibited similar activity in samples from patients with blast crisis CML.
“Our results demonstrate that . . . employing combined blockade of BCL-2 and BCR-ABL has the potential for curing CML and significantly improving outcomes for patients with blast crisis, and, as such, warrants clinical testing,” said Michael Andreeff, MD, of the University of Texas MD Anderson Cancer Center in Houston.
Dr Andreeff and his colleagues reported these results in Science Translational Medicine. The study was funded by National Institutes of Health, the Paul and Mary Haas Chair in Genetics, and Abbvie Inc., the company developing venetoclax.
The researchers noted that, although BCR-ABL TKIs have proven effective against CML, they rarely eliminate CML stem cells.
“It is believed that TKIs do not eliminate residual stem cells because they are not dependent on BCR-ABL signaling,” said study author Bing Carter, PhD, also of MD Anderson Cancer Center. “Hence, cures of CML with TKIs are rare.”
Dr Carter has worked for several years on eliminating residual CML stem cells, which could mean CML patients would no longer require long-term treatment with TKIs. Based on the current study, she and her colleagues believe that combining a TKI with a BCL-2 inhibitor may be a solution.
The researchers found that targeting both BCL-2 and BCR-ABL with venetoclax and nilotinib, respectively, exerted “potent antileukemic activity” and prolonged survival in BCR-ABL transgenic mice.
After stopping treatment, the median survival was 34.5 days for control mice, 70 days for mice treated with nilotinib alone (P=0.2146), 115 days for mice treated with venetoclax alone (P=0.0079), and 168 days for mice treated with nilotinib and venetoclax in combination (P=0.0002).
Subsequent experiments in mice showed that nilotinib alone did not significantly affect the frequency of long-term LSCs, although venetoclax alone did. Treatment with both drugs reduced the frequency of long-term LSCs even more than venetoclax alone.
Finally, the researchers tested venetoclax, nilotinib, and the combination in cells from 6 patients with blast crisis CML, all of whom had failed treatment with at least 1 TKI.
The team found that venetoclax and nilotinib had a synergistic apoptotic effect on bulk and stem/progenitor CML cells.
The researchers said these results suggest that combined inhibition of BCL-2 and BCR-ABL tyrosine kinase has the potential to significantly improve the depth of response and cure rates of chronic phase and blast crisis CML.
“This combination strategy may also apply to other malignancies that depend on kinase signaling for progression and maintenance,” Dr Andreeff added.
How AML suppresses hematopoiesis
Exosomes shed by acute myeloid leukemia (AML) cells carry microRNAs that directly impair hematopoiesis, according to preclinical research published in Science Signaling.
Previous research suggested that AML exosomes can suppress residual hematopoietic stem and progenitor cell (HSPC) function indirectly through stromal reprogramming of niche retention factors.
The new study indicates that AML exosomes can block hematopoiesis by delivering microRNAs that directly suppress blood production when taken up by HSPCs.
Noah Hornick, of Oregon Health & Science University in Portland, and his colleagues conducted this study, isolating exosomes from cultures of human AML cells and from the plasma of mice with AML.
The researchers found these exosomes were enriched in 2 microRNAs—miR-150 and miR-155.
When cultured with HSPCs, the exosomes suppressed the expression of the transcription factor c-MYB, which is involved in HSPC proliferation and differentiation.
Blocking the function of miR-155 prevented AML cells or their exosomes from reducing c-MYB abundance and inhibiting the proliferation of cultured HSPCs.
Using a method called RISC-Trap, the researchers identified other targets of microRNAs in AML exosomes, from which they predicted protein networks that could be disrupted in cells taking up the exosomes.
The team said this study suggests that interfering with exosome-delivered microRNAs in the bone marrow or restoring the abundance of their targets may enhance AML patients’ ability to produce healthy blood cells.
Exosomes shed by acute myeloid leukemia (AML) cells carry microRNAs that directly impair hematopoiesis, according to preclinical research published in Science Signaling.
Previous research suggested that AML exosomes can suppress residual hematopoietic stem and progenitor cell (HSPC) function indirectly through stromal reprogramming of niche retention factors.
The new study indicates that AML exosomes can block hematopoiesis by delivering microRNAs that directly suppress blood production when taken up by HSPCs.
Noah Hornick, of Oregon Health & Science University in Portland, and his colleagues conducted this study, isolating exosomes from cultures of human AML cells and from the plasma of mice with AML.
The researchers found these exosomes were enriched in 2 microRNAs—miR-150 and miR-155.
When cultured with HSPCs, the exosomes suppressed the expression of the transcription factor c-MYB, which is involved in HSPC proliferation and differentiation.
Blocking the function of miR-155 prevented AML cells or their exosomes from reducing c-MYB abundance and inhibiting the proliferation of cultured HSPCs.
Using a method called RISC-Trap, the researchers identified other targets of microRNAs in AML exosomes, from which they predicted protein networks that could be disrupted in cells taking up the exosomes.
The team said this study suggests that interfering with exosome-delivered microRNAs in the bone marrow or restoring the abundance of their targets may enhance AML patients’ ability to produce healthy blood cells.
Exosomes shed by acute myeloid leukemia (AML) cells carry microRNAs that directly impair hematopoiesis, according to preclinical research published in Science Signaling.
Previous research suggested that AML exosomes can suppress residual hematopoietic stem and progenitor cell (HSPC) function indirectly through stromal reprogramming of niche retention factors.
The new study indicates that AML exosomes can block hematopoiesis by delivering microRNAs that directly suppress blood production when taken up by HSPCs.
Noah Hornick, of Oregon Health & Science University in Portland, and his colleagues conducted this study, isolating exosomes from cultures of human AML cells and from the plasma of mice with AML.
The researchers found these exosomes were enriched in 2 microRNAs—miR-150 and miR-155.
When cultured with HSPCs, the exosomes suppressed the expression of the transcription factor c-MYB, which is involved in HSPC proliferation and differentiation.
Blocking the function of miR-155 prevented AML cells or their exosomes from reducing c-MYB abundance and inhibiting the proliferation of cultured HSPCs.
Using a method called RISC-Trap, the researchers identified other targets of microRNAs in AML exosomes, from which they predicted protein networks that could be disrupted in cells taking up the exosomes.
The team said this study suggests that interfering with exosome-delivered microRNAs in the bone marrow or restoring the abundance of their targets may enhance AML patients’ ability to produce healthy blood cells.
CBT may be best option for pts with MRD, doc says
Photo courtesy of NHS
A cord blood transplant (CBT) may be the best option for patients with acute leukemia or myelodysplastic syndrome who have minimal residual disease (MRD) and no related donor, according to the senior author of a study published in NEJM.
This retrospective study showed that patients with MRD at the time of transplant were less likely to relapse if they received CBT rather than a graft from an unrelated adult donor, whether HLA-matched or mismatched.
In addition, the risk of death was significantly higher for patients with a mismatched donor than for CBT recipients, although there was no significant difference between those with a matched donor and CBT recipients.
Among patients without MRD, there were no significant differences between the transplant types for the risk of relapse or death.
“This paper shows that if you’ve got high-risk disease and are at high risk for relapse post-transplant, transplant with a cord blood donor may be the best option,” said Colleen Delaney, MD, of Fred Hutchinson Cancer Research Center in Seattle, Washington.
Dr Delaney and her colleagues analyzed data on 582 patients—300 with acute myeloid leukemia, 185 with acute lymphoblastic leukemia, and 97 with myelodysplastic syndromes.
Most patients received a transplant from an HLA-matched unrelated donor (n=344), 140 received a CBT from an unrelated donor, and 98 received a transplant from an HLA-mismatched unrelated donor.
The researchers calculated the relative risks of death and relapse for each transplant group, and they found that a patient’s MRD status prior to transplant played a role.
Presence of MRD
Among patients with MRD, the risk of death was significantly higher for recipients of mismatched grafts than for CBT recipients, with a hazard ratio (HR) of 2.92 (P=0.001).
However, the risk of death was not significantly different for recipients of matched grafts compared to CBT recipients. The HR was 1.69 (P=0.08).
The risk of relapse was about 3 times higher for recipients of mismatched grafts (HR=3.01, P=0.02) or matched grafts (HR=2.92, P=0.007) than for CBT recipients.
No MRD
Among patients without MRD, there was no significant difference in the risk of death for recipients of CBT, mismatched grafts (HR=1.36, P=0.30), or matched grafts (HR=0.78, P=0.33).
And there was no significant difference in the risk of relapse for recipients of CBT, mismatched grafts (HR=1.28, P=0.60), or matched grafts (HR=1.30, P=0.46).
“This brings home the point that cord blood shouldn’t be called an alternative donor,” Dr Delaney said. “The outcomes are the same as a conventional donor.”
Photo courtesy of NHS
A cord blood transplant (CBT) may be the best option for patients with acute leukemia or myelodysplastic syndrome who have minimal residual disease (MRD) and no related donor, according to the senior author of a study published in NEJM.
This retrospective study showed that patients with MRD at the time of transplant were less likely to relapse if they received CBT rather than a graft from an unrelated adult donor, whether HLA-matched or mismatched.
In addition, the risk of death was significantly higher for patients with a mismatched donor than for CBT recipients, although there was no significant difference between those with a matched donor and CBT recipients.
Among patients without MRD, there were no significant differences between the transplant types for the risk of relapse or death.
“This paper shows that if you’ve got high-risk disease and are at high risk for relapse post-transplant, transplant with a cord blood donor may be the best option,” said Colleen Delaney, MD, of Fred Hutchinson Cancer Research Center in Seattle, Washington.
Dr Delaney and her colleagues analyzed data on 582 patients—300 with acute myeloid leukemia, 185 with acute lymphoblastic leukemia, and 97 with myelodysplastic syndromes.
Most patients received a transplant from an HLA-matched unrelated donor (n=344), 140 received a CBT from an unrelated donor, and 98 received a transplant from an HLA-mismatched unrelated donor.
The researchers calculated the relative risks of death and relapse for each transplant group, and they found that a patient’s MRD status prior to transplant played a role.
Presence of MRD
Among patients with MRD, the risk of death was significantly higher for recipients of mismatched grafts than for CBT recipients, with a hazard ratio (HR) of 2.92 (P=0.001).
However, the risk of death was not significantly different for recipients of matched grafts compared to CBT recipients. The HR was 1.69 (P=0.08).
The risk of relapse was about 3 times higher for recipients of mismatched grafts (HR=3.01, P=0.02) or matched grafts (HR=2.92, P=0.007) than for CBT recipients.
No MRD
Among patients without MRD, there was no significant difference in the risk of death for recipients of CBT, mismatched grafts (HR=1.36, P=0.30), or matched grafts (HR=0.78, P=0.33).
And there was no significant difference in the risk of relapse for recipients of CBT, mismatched grafts (HR=1.28, P=0.60), or matched grafts (HR=1.30, P=0.46).
“This brings home the point that cord blood shouldn’t be called an alternative donor,” Dr Delaney said. “The outcomes are the same as a conventional donor.”
Photo courtesy of NHS
A cord blood transplant (CBT) may be the best option for patients with acute leukemia or myelodysplastic syndrome who have minimal residual disease (MRD) and no related donor, according to the senior author of a study published in NEJM.
This retrospective study showed that patients with MRD at the time of transplant were less likely to relapse if they received CBT rather than a graft from an unrelated adult donor, whether HLA-matched or mismatched.
In addition, the risk of death was significantly higher for patients with a mismatched donor than for CBT recipients, although there was no significant difference between those with a matched donor and CBT recipients.
Among patients without MRD, there were no significant differences between the transplant types for the risk of relapse or death.
“This paper shows that if you’ve got high-risk disease and are at high risk for relapse post-transplant, transplant with a cord blood donor may be the best option,” said Colleen Delaney, MD, of Fred Hutchinson Cancer Research Center in Seattle, Washington.
Dr Delaney and her colleagues analyzed data on 582 patients—300 with acute myeloid leukemia, 185 with acute lymphoblastic leukemia, and 97 with myelodysplastic syndromes.
Most patients received a transplant from an HLA-matched unrelated donor (n=344), 140 received a CBT from an unrelated donor, and 98 received a transplant from an HLA-mismatched unrelated donor.
The researchers calculated the relative risks of death and relapse for each transplant group, and they found that a patient’s MRD status prior to transplant played a role.
Presence of MRD
Among patients with MRD, the risk of death was significantly higher for recipients of mismatched grafts than for CBT recipients, with a hazard ratio (HR) of 2.92 (P=0.001).
However, the risk of death was not significantly different for recipients of matched grafts compared to CBT recipients. The HR was 1.69 (P=0.08).
The risk of relapse was about 3 times higher for recipients of mismatched grafts (HR=3.01, P=0.02) or matched grafts (HR=2.92, P=0.007) than for CBT recipients.
No MRD
Among patients without MRD, there was no significant difference in the risk of death for recipients of CBT, mismatched grafts (HR=1.36, P=0.30), or matched grafts (HR=0.78, P=0.33).
And there was no significant difference in the risk of relapse for recipients of CBT, mismatched grafts (HR=1.28, P=0.60), or matched grafts (HR=1.30, P=0.46).
“This brings home the point that cord blood shouldn’t be called an alternative donor,” Dr Delaney said. “The outcomes are the same as a conventional donor.”
HSCT may age T cells as much as 30 years
Photo by Chad McNeeley
New research suggests hematopoietic stem cell transplant (HSCT) may increase the molecular age of peripheral blood T cells.
The study showed an increase in peripheral blood T-cell senescence in patients with hematologic malignancies who were treated with autologous (auto-) or allogeneic (allo-) HSCT.
The patients had elevated levels of p16INK4a, a known marker of cellular senescence.
Auto-HSCT in particular had a strong effect on p16INK4a, increasing the expression of this marker to a degree comparable to 30 years of chronological aging.
Researchers reported these findings in EBioMedicine.
“We know that transplant is life-prolonging, and, in many cases, it’s life-saving for many patients with blood cancers and other disorders,” said study author William Wood, MD, of the University of North Carolina School of Medicine in Chapel Hill.
“At the same time, we’re increasingly recognizing that survivors of transplant are at risk for long-term health problems, and so there is interest in determining what markers may exist to help predict risk for long-term health problems or even in helping choose which patients are best candidates for transplantation.”
With this in mind, Dr Wood and his colleagues looked at levels of p16INK4a in 63 patients who underwent auto- or allo-HSCT to treat myeloma, lymphoma, or leukemia. The researchers assessed p16INK4a expression in T cells before HSCT and 6 months after.
Among auto-HSCT recipients, there were no baseline characteristics associated with pre-transplant p16INK4a expression.
However, allo-HSCT recipients had significantly higher pre-transplant p16INK4a levels the more cycles of chemotherapy they received before transplant (P=0.003), if they had previously undergone auto-HSCT (P=0.01), and if they had been exposed to alkylating agents (P=0.01).
After transplant, allo-HSCT recipients had a 1.93-fold increase in p16INK4a expression (P=0.0004), and auto-HSCT recipients had a 3.05-fold increase (P=0.002).
The researchers said the measured change in p16INK4a from pre- to post-HSCT in allogeneic recipients likely underestimates the age-promoting effects of HSCT, given that the pre-HSCT levels were elevated in the recipients from prior therapeutic exposure.
The researchers also pointed out that this study does not show a clear connection between changes in p16INK4a levels and the actual function of peripheral blood T cells, but they did say that p16INK4a is “arguably one of the best in vivo markers of cellular senescence and is directly associated with age-related deterioration.”
So the results of this research suggest the forced bone marrow repopulation associated with HSCT accelerates the molecular aging of peripheral blood T cells.
“Many oncologists would not be surprised by the finding that stem cell transplant accelerates aspects of aging,” said study author Norman Sharpless, MD, of the University of North Carolina School of Medicine.
“We know that, years after a curative transplant, stem cell transplant survivors are at increased risk for blood problems that can occur with aging, such as reduced immunity, increased risk for bone marrow failure, and increased risk of blood cancers. What is important about this work, however, is that it allows us to quantify the effect of stem cell transplant on molecular age.”
Photo by Chad McNeeley
New research suggests hematopoietic stem cell transplant (HSCT) may increase the molecular age of peripheral blood T cells.
The study showed an increase in peripheral blood T-cell senescence in patients with hematologic malignancies who were treated with autologous (auto-) or allogeneic (allo-) HSCT.
The patients had elevated levels of p16INK4a, a known marker of cellular senescence.
Auto-HSCT in particular had a strong effect on p16INK4a, increasing the expression of this marker to a degree comparable to 30 years of chronological aging.
Researchers reported these findings in EBioMedicine.
“We know that transplant is life-prolonging, and, in many cases, it’s life-saving for many patients with blood cancers and other disorders,” said study author William Wood, MD, of the University of North Carolina School of Medicine in Chapel Hill.
“At the same time, we’re increasingly recognizing that survivors of transplant are at risk for long-term health problems, and so there is interest in determining what markers may exist to help predict risk for long-term health problems or even in helping choose which patients are best candidates for transplantation.”
With this in mind, Dr Wood and his colleagues looked at levels of p16INK4a in 63 patients who underwent auto- or allo-HSCT to treat myeloma, lymphoma, or leukemia. The researchers assessed p16INK4a expression in T cells before HSCT and 6 months after.
Among auto-HSCT recipients, there were no baseline characteristics associated with pre-transplant p16INK4a expression.
However, allo-HSCT recipients had significantly higher pre-transplant p16INK4a levels the more cycles of chemotherapy they received before transplant (P=0.003), if they had previously undergone auto-HSCT (P=0.01), and if they had been exposed to alkylating agents (P=0.01).
After transplant, allo-HSCT recipients had a 1.93-fold increase in p16INK4a expression (P=0.0004), and auto-HSCT recipients had a 3.05-fold increase (P=0.002).
The researchers said the measured change in p16INK4a from pre- to post-HSCT in allogeneic recipients likely underestimates the age-promoting effects of HSCT, given that the pre-HSCT levels were elevated in the recipients from prior therapeutic exposure.
The researchers also pointed out that this study does not show a clear connection between changes in p16INK4a levels and the actual function of peripheral blood T cells, but they did say that p16INK4a is “arguably one of the best in vivo markers of cellular senescence and is directly associated with age-related deterioration.”
So the results of this research suggest the forced bone marrow repopulation associated with HSCT accelerates the molecular aging of peripheral blood T cells.
“Many oncologists would not be surprised by the finding that stem cell transplant accelerates aspects of aging,” said study author Norman Sharpless, MD, of the University of North Carolina School of Medicine.
“We know that, years after a curative transplant, stem cell transplant survivors are at increased risk for blood problems that can occur with aging, such as reduced immunity, increased risk for bone marrow failure, and increased risk of blood cancers. What is important about this work, however, is that it allows us to quantify the effect of stem cell transplant on molecular age.”
Photo by Chad McNeeley
New research suggests hematopoietic stem cell transplant (HSCT) may increase the molecular age of peripheral blood T cells.
The study showed an increase in peripheral blood T-cell senescence in patients with hematologic malignancies who were treated with autologous (auto-) or allogeneic (allo-) HSCT.
The patients had elevated levels of p16INK4a, a known marker of cellular senescence.
Auto-HSCT in particular had a strong effect on p16INK4a, increasing the expression of this marker to a degree comparable to 30 years of chronological aging.
Researchers reported these findings in EBioMedicine.
“We know that transplant is life-prolonging, and, in many cases, it’s life-saving for many patients with blood cancers and other disorders,” said study author William Wood, MD, of the University of North Carolina School of Medicine in Chapel Hill.
“At the same time, we’re increasingly recognizing that survivors of transplant are at risk for long-term health problems, and so there is interest in determining what markers may exist to help predict risk for long-term health problems or even in helping choose which patients are best candidates for transplantation.”
With this in mind, Dr Wood and his colleagues looked at levels of p16INK4a in 63 patients who underwent auto- or allo-HSCT to treat myeloma, lymphoma, or leukemia. The researchers assessed p16INK4a expression in T cells before HSCT and 6 months after.
Among auto-HSCT recipients, there were no baseline characteristics associated with pre-transplant p16INK4a expression.
However, allo-HSCT recipients had significantly higher pre-transplant p16INK4a levels the more cycles of chemotherapy they received before transplant (P=0.003), if they had previously undergone auto-HSCT (P=0.01), and if they had been exposed to alkylating agents (P=0.01).
After transplant, allo-HSCT recipients had a 1.93-fold increase in p16INK4a expression (P=0.0004), and auto-HSCT recipients had a 3.05-fold increase (P=0.002).
The researchers said the measured change in p16INK4a from pre- to post-HSCT in allogeneic recipients likely underestimates the age-promoting effects of HSCT, given that the pre-HSCT levels were elevated in the recipients from prior therapeutic exposure.
The researchers also pointed out that this study does not show a clear connection between changes in p16INK4a levels and the actual function of peripheral blood T cells, but they did say that p16INK4a is “arguably one of the best in vivo markers of cellular senescence and is directly associated with age-related deterioration.”
So the results of this research suggest the forced bone marrow repopulation associated with HSCT accelerates the molecular aging of peripheral blood T cells.
“Many oncologists would not be surprised by the finding that stem cell transplant accelerates aspects of aging,” said study author Norman Sharpless, MD, of the University of North Carolina School of Medicine.
“We know that, years after a curative transplant, stem cell transplant survivors are at increased risk for blood problems that can occur with aging, such as reduced immunity, increased risk for bone marrow failure, and increased risk of blood cancers. What is important about this work, however, is that it allows us to quantify the effect of stem cell transplant on molecular age.”