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Study: Complications from childhood ALL and its treatment are common, but can be managed
Despite survival after treatment of acute lymphoblastic leukemia (ALL), a high percentage of children suffered acute complications, even without relapse, according to a report published online in Clinical Lymphoma, Myeloma & Leukemia.
In a retrospective study of 110 children with acute lymphoblastic leukemia (ALL), Ayse Pınar Öztürk, MD, and colleagues at Istanbul University, Cerrahpasa Faculty of Medicine, evaluated the acute complications that occurred during the treatment of childhood ALL and documented their survival rates. The 110 patients, comprising 65 boys and 45 girls, were all treated with the Children’s Oncology Group protocol from 1999 to 2014.
The mean age at admission was 8.3 years and 97 patients (88.2%) were diagnosed with pre–B-cell ALL, 11 (10%) with T-cell ALL, 1 (0.9%) with mixed phenotype acute leukemia, and 1 (0.9%) with mature B-cell acute leukemia. A total of 36.3% were evaluated to be in the standard-risk group and the rest were in the high-risk group. Regular follow-up and evaluation for acute complications was available for 105 of the patients.
Survival and complications
Of the 110 patients, 98 were assessed in the survival analyses. The 5- and 10-year overall survival rates were both 85.9%, while the relapse-free survival rates at 1, 3, and 5 years were 97.9%, 91.3%, and 86.3%, respectively. These results are favorable and in line with good results reported in the literature, according to the researchers.
In terms of acute complications, infection was the most common (88.5%), followed by gastrointestinal (27.6%), neurologic (26.6%), metabolic/endocrine (15.2%), drug-related hypersensitivity (15.2%), avascular necrosis (12.3%), thrombotic (10.4%), severe psychiatric (1.9%), and various other complications (11.4%).
In the present study, 13 of the 98 patients (13.3%) died. All 13 patients had been in the high-risk group and 9 had had relapsed ALL. Of the 13 deaths, 8 (8.2%) had resulted from treatment resistance and toxicity and 5 (5.1%) from severe infection (sepsis).
During ALL treatment, various complications can occur related to the disease itself or the treatment, according to the authors. However, they added that in regularly and closely monitored patients, complications can be effectively prevented, treated, and eliminated by aggressive observation and prompt intervention.
“In our study, the short hospitalization period, prompt implementation of protocol updates, rapid analysis of laboratory tests, continuous supportive care, efficient education given to the parents of children, and consistently undertaking patient care and treatment management by the same expert team increased the success of the therapy and ensured low complication rates,” the researchers concluded.
The authors reported that they had no conflicts of interest.
SOURCE: Öztürk AP et al. Clin Lymphoma Myeloma Leuk. 2020 Sep 17. doi: 10.1016/j.clml.2020.08.025.
Despite survival after treatment of acute lymphoblastic leukemia (ALL), a high percentage of children suffered acute complications, even without relapse, according to a report published online in Clinical Lymphoma, Myeloma & Leukemia.
In a retrospective study of 110 children with acute lymphoblastic leukemia (ALL), Ayse Pınar Öztürk, MD, and colleagues at Istanbul University, Cerrahpasa Faculty of Medicine, evaluated the acute complications that occurred during the treatment of childhood ALL and documented their survival rates. The 110 patients, comprising 65 boys and 45 girls, were all treated with the Children’s Oncology Group protocol from 1999 to 2014.
The mean age at admission was 8.3 years and 97 patients (88.2%) were diagnosed with pre–B-cell ALL, 11 (10%) with T-cell ALL, 1 (0.9%) with mixed phenotype acute leukemia, and 1 (0.9%) with mature B-cell acute leukemia. A total of 36.3% were evaluated to be in the standard-risk group and the rest were in the high-risk group. Regular follow-up and evaluation for acute complications was available for 105 of the patients.
Survival and complications
Of the 110 patients, 98 were assessed in the survival analyses. The 5- and 10-year overall survival rates were both 85.9%, while the relapse-free survival rates at 1, 3, and 5 years were 97.9%, 91.3%, and 86.3%, respectively. These results are favorable and in line with good results reported in the literature, according to the researchers.
In terms of acute complications, infection was the most common (88.5%), followed by gastrointestinal (27.6%), neurologic (26.6%), metabolic/endocrine (15.2%), drug-related hypersensitivity (15.2%), avascular necrosis (12.3%), thrombotic (10.4%), severe psychiatric (1.9%), and various other complications (11.4%).
In the present study, 13 of the 98 patients (13.3%) died. All 13 patients had been in the high-risk group and 9 had had relapsed ALL. Of the 13 deaths, 8 (8.2%) had resulted from treatment resistance and toxicity and 5 (5.1%) from severe infection (sepsis).
During ALL treatment, various complications can occur related to the disease itself or the treatment, according to the authors. However, they added that in regularly and closely monitored patients, complications can be effectively prevented, treated, and eliminated by aggressive observation and prompt intervention.
“In our study, the short hospitalization period, prompt implementation of protocol updates, rapid analysis of laboratory tests, continuous supportive care, efficient education given to the parents of children, and consistently undertaking patient care and treatment management by the same expert team increased the success of the therapy and ensured low complication rates,” the researchers concluded.
The authors reported that they had no conflicts of interest.
SOURCE: Öztürk AP et al. Clin Lymphoma Myeloma Leuk. 2020 Sep 17. doi: 10.1016/j.clml.2020.08.025.
Despite survival after treatment of acute lymphoblastic leukemia (ALL), a high percentage of children suffered acute complications, even without relapse, according to a report published online in Clinical Lymphoma, Myeloma & Leukemia.
In a retrospective study of 110 children with acute lymphoblastic leukemia (ALL), Ayse Pınar Öztürk, MD, and colleagues at Istanbul University, Cerrahpasa Faculty of Medicine, evaluated the acute complications that occurred during the treatment of childhood ALL and documented their survival rates. The 110 patients, comprising 65 boys and 45 girls, were all treated with the Children’s Oncology Group protocol from 1999 to 2014.
The mean age at admission was 8.3 years and 97 patients (88.2%) were diagnosed with pre–B-cell ALL, 11 (10%) with T-cell ALL, 1 (0.9%) with mixed phenotype acute leukemia, and 1 (0.9%) with mature B-cell acute leukemia. A total of 36.3% were evaluated to be in the standard-risk group and the rest were in the high-risk group. Regular follow-up and evaluation for acute complications was available for 105 of the patients.
Survival and complications
Of the 110 patients, 98 were assessed in the survival analyses. The 5- and 10-year overall survival rates were both 85.9%, while the relapse-free survival rates at 1, 3, and 5 years were 97.9%, 91.3%, and 86.3%, respectively. These results are favorable and in line with good results reported in the literature, according to the researchers.
In terms of acute complications, infection was the most common (88.5%), followed by gastrointestinal (27.6%), neurologic (26.6%), metabolic/endocrine (15.2%), drug-related hypersensitivity (15.2%), avascular necrosis (12.3%), thrombotic (10.4%), severe psychiatric (1.9%), and various other complications (11.4%).
In the present study, 13 of the 98 patients (13.3%) died. All 13 patients had been in the high-risk group and 9 had had relapsed ALL. Of the 13 deaths, 8 (8.2%) had resulted from treatment resistance and toxicity and 5 (5.1%) from severe infection (sepsis).
During ALL treatment, various complications can occur related to the disease itself or the treatment, according to the authors. However, they added that in regularly and closely monitored patients, complications can be effectively prevented, treated, and eliminated by aggressive observation and prompt intervention.
“In our study, the short hospitalization period, prompt implementation of protocol updates, rapid analysis of laboratory tests, continuous supportive care, efficient education given to the parents of children, and consistently undertaking patient care and treatment management by the same expert team increased the success of the therapy and ensured low complication rates,” the researchers concluded.
The authors reported that they had no conflicts of interest.
SOURCE: Öztürk AP et al. Clin Lymphoma Myeloma Leuk. 2020 Sep 17. doi: 10.1016/j.clml.2020.08.025.
FROM Clinical Lymphoma, Myeloma & Leukemia
Orthopedic problems in children can be the first indication of acute lymphoblastic leukemia
The diagnosis of acute lymphoblastic leukemia (ALL) can be delayed because of vague presentation and normal hematological results. Orthopedic manifestations may be the primary presentation of ALL to physicians, and such symptoms in children should be cause for suspicion, even in the absence of hematological abnormalities, according to a report published in the Journal of Orthopaedics.
The study retrospectively assessed 250 consecutive ALL patients at a single institution to identify the frequency of ALL cases presented to the orthopedic department and to determine the number of these patients presenting with normal hematological results, according to Amrath Raj BK, MD, and colleagues at the Manipal (India) Academy of Higher Education.
Suspicion warranted
Twenty-two of the 250 patients (8.8%) presented primarily to the orthopedic department (4 with vertebral compression fractures, 12 with joint pain, and 6 with bone pain), but were subsequently diagnosed with ALL. These results were comparable to previous studies. The mean patient age at the first visit was 5.6 years; 13 patients were boys, and 9 were girls. Six of these 22 patients (27.3%) had a normal peripheral blood smear, according to the researchers.
“Acute leukemia should be considered strongly as a differential diagnosis in children with severe osteoporosis and vertebral fractures. Initial orthopedic manifestations are not uncommon, and the primary physician should maintain a high index of suspicion as a peripheral smear is not diagnostic in all patients,” the researchers concluded.
The authors reported that there was no outside funding source and that they had no conflicts.
SOURCE: Raj BK A et al. Journal of Orthopaedics. 2020;22:326-330.
The diagnosis of acute lymphoblastic leukemia (ALL) can be delayed because of vague presentation and normal hematological results. Orthopedic manifestations may be the primary presentation of ALL to physicians, and such symptoms in children should be cause for suspicion, even in the absence of hematological abnormalities, according to a report published in the Journal of Orthopaedics.
The study retrospectively assessed 250 consecutive ALL patients at a single institution to identify the frequency of ALL cases presented to the orthopedic department and to determine the number of these patients presenting with normal hematological results, according to Amrath Raj BK, MD, and colleagues at the Manipal (India) Academy of Higher Education.
Suspicion warranted
Twenty-two of the 250 patients (8.8%) presented primarily to the orthopedic department (4 with vertebral compression fractures, 12 with joint pain, and 6 with bone pain), but were subsequently diagnosed with ALL. These results were comparable to previous studies. The mean patient age at the first visit was 5.6 years; 13 patients were boys, and 9 were girls. Six of these 22 patients (27.3%) had a normal peripheral blood smear, according to the researchers.
“Acute leukemia should be considered strongly as a differential diagnosis in children with severe osteoporosis and vertebral fractures. Initial orthopedic manifestations are not uncommon, and the primary physician should maintain a high index of suspicion as a peripheral smear is not diagnostic in all patients,” the researchers concluded.
The authors reported that there was no outside funding source and that they had no conflicts.
SOURCE: Raj BK A et al. Journal of Orthopaedics. 2020;22:326-330.
The diagnosis of acute lymphoblastic leukemia (ALL) can be delayed because of vague presentation and normal hematological results. Orthopedic manifestations may be the primary presentation of ALL to physicians, and such symptoms in children should be cause for suspicion, even in the absence of hematological abnormalities, according to a report published in the Journal of Orthopaedics.
The study retrospectively assessed 250 consecutive ALL patients at a single institution to identify the frequency of ALL cases presented to the orthopedic department and to determine the number of these patients presenting with normal hematological results, according to Amrath Raj BK, MD, and colleagues at the Manipal (India) Academy of Higher Education.
Suspicion warranted
Twenty-two of the 250 patients (8.8%) presented primarily to the orthopedic department (4 with vertebral compression fractures, 12 with joint pain, and 6 with bone pain), but were subsequently diagnosed with ALL. These results were comparable to previous studies. The mean patient age at the first visit was 5.6 years; 13 patients were boys, and 9 were girls. Six of these 22 patients (27.3%) had a normal peripheral blood smear, according to the researchers.
“Acute leukemia should be considered strongly as a differential diagnosis in children with severe osteoporosis and vertebral fractures. Initial orthopedic manifestations are not uncommon, and the primary physician should maintain a high index of suspicion as a peripheral smear is not diagnostic in all patients,” the researchers concluded.
The authors reported that there was no outside funding source and that they had no conflicts.
SOURCE: Raj BK A et al. Journal of Orthopaedics. 2020;22:326-330.
FROM THE JOURNAL OF ORTHOPAEDICS
Survey quantifies COVID-19’s impact on oncology
An international survey provides new insights into how COVID-19 has affected, and may continue to affect, the field of oncology.
The survey showed that “COVID-19 has had a major impact on the organization of patient care, on the well-being of caregivers, on continued medical education, and on clinical trial activities in oncology,” stated Guy Jerusalem, MD, PhD, of Centre Hospitalier Universitaire de Liège (Belgium).
Dr. Jerusalem presented these findings at the European Society for Medical Oncology Virtual Congress 2020.
The survey was distributed by 20 oncologists from 10 of the countries most affected by COVID-19. Responses were obtained from 109 oncologists representing centers in 18 countries. The responses were recorded between June 17 and July 14, 2020.
The survey consisted of 95 items intended to evaluate the impact of COVID-19 on the organization of oncologic care. Questions encompassed the capacity and service offered at each center, the magnitude of COVID-19–based care interruptions and the reasons for them, the ensuing challenges faced, interventions implemented, and the estimated harms to patients during the pandemic.
The 109 oncologists surveyed had a median of 20 years of oncology experience. A majority of respondents were men (61.5%), and the median age was 48.5 years.
The respondents had worked predominantly (62.4%) at academic hospitals, with 29.6% at community hospitals. Most respondents worked at general hospitals with an oncology unit (66.1%) rather than a specialized separate cancer center (32.1%).
The most common specialty was breast cancer (60.6%), followed by gastrointestinal cancer (10.1%), urogenital cancer (9.2%), and lung cancer (8.3%).
Impact on treatment
The treatment modalities affected by the pandemic – through cancellations or delays in more than 10% of patients – included surgery (in 34% of centers), chemotherapy (22%), radiotherapy (13.7%), checkpoint inhibitor therapy (9.1%), monoclonal antibodies (9%), and oral targeted therapy (3.7%).
Among oncologists treating breast cancer, cancellations/delays in more than 10% of patients were reported for everolimus (18%), CDK4/6 inhibitors (8.9%), and endocrine therapy (2.2%).
Overall, 34.8% of respondents reported increased use of granulocyte colony–stimulating factor, and 6.4% reported increased use of erythropoietin.
On the other hand, 11.1% of respondents reported a decrease in the use of double immunotherapy, and 21.9% reported decreased use of corticosteroids.
Not only can the immunosuppressive effects of steroid use increase infection risks, Dr. Jerusalem noted, fever suppression can lead to a delayed diagnosis of COVID-19.
“To circumvent potential higher infection risks or greater disease severity, we use lower doses of steroids, but this is not based on studies,” he said.
“Previous exposure to steroids or being on steroids at the time of COVID-19 infection is a detrimental factor for complications and mortality,” commented ESMO President Solange Peters, MD, PhD, of Centre Hospitalier Universitaire Vaudois in Lausanne, Switzerland.
Dr. Peters noted that the observation was based on lung cancer registry findings. Furthermore, because data from smaller outbreaks of other coronavirus infections suggested worse prognosis and increased mortality, steroid use was already feared in the very early days of the COVID-19 pandemic.
Lastly, earlier cessation of palliative treatment was observed in 32.1% of centers, and 64.2% of respondents agreed that undertreatment because of COVID-19 is a major concern.
Dr. Jerusalem noted that the survey data do not explain the early cessation of palliative treatment. “I suspect that many patients died at home rather than alone in institutions because it was the only way they could die with their families around them.”
Telehealth, meetings, and trials
The survey also revealed rationales for the use of teleconsultation, including follow-up (94.5%), oral therapy (92.7%), immunotherapy (57.8%), and chemotherapy (55%).
Most respondents reported more frequent use of virtual meetings for continuing medical education (94%), oncologic team meetings (92%), and tumor boards (82%).
While about 82% of respondents said they were likely to continue the use of telemedicine, 45% said virtual conferences are not an acceptable alternative to live international conferences such as ESMO, Dr. Jerusalem said.
Finally, nearly three-quarters of respondents (72.5%) said all clinical trial activities are or will soon be activated, or never stopped, at their centers. On the other hand, 27.5% of respondents reported that their centers had major protocol violations or deviations, and 37% of respondents said they expect significant reductions in clinical trial activities this year.
Dr. Jerusalem concluded that COVID-19 is having a major, long-term impact on the organization of patient care, caregivers, continued medical education, and clinical trial activities in oncology.
He cautioned that “the risk of a delayed diagnosis of new cancers and economic consequences of COVID-19 on access to health care and cancer treatments have to be carefully evaluated.”
This research was funded by Fondation Léon Fredericq. Dr. Jerusalem disclosed relationships with Novartis, Roche, Lilly, Pfizer, Amgen, Bristol-Myers Squibb, AstraZeneca, Daiichi Sankyo, AbbVie, MedImmune, and Merck. Dr. Peters disclosed relationships with AbbVie, Amgen, AstraZeneca, and many other companies.
SOURCE: Jerusalem G et al. ESMO 2020, Abstract LBA76.
An international survey provides new insights into how COVID-19 has affected, and may continue to affect, the field of oncology.
The survey showed that “COVID-19 has had a major impact on the organization of patient care, on the well-being of caregivers, on continued medical education, and on clinical trial activities in oncology,” stated Guy Jerusalem, MD, PhD, of Centre Hospitalier Universitaire de Liège (Belgium).
Dr. Jerusalem presented these findings at the European Society for Medical Oncology Virtual Congress 2020.
The survey was distributed by 20 oncologists from 10 of the countries most affected by COVID-19. Responses were obtained from 109 oncologists representing centers in 18 countries. The responses were recorded between June 17 and July 14, 2020.
The survey consisted of 95 items intended to evaluate the impact of COVID-19 on the organization of oncologic care. Questions encompassed the capacity and service offered at each center, the magnitude of COVID-19–based care interruptions and the reasons for them, the ensuing challenges faced, interventions implemented, and the estimated harms to patients during the pandemic.
The 109 oncologists surveyed had a median of 20 years of oncology experience. A majority of respondents were men (61.5%), and the median age was 48.5 years.
The respondents had worked predominantly (62.4%) at academic hospitals, with 29.6% at community hospitals. Most respondents worked at general hospitals with an oncology unit (66.1%) rather than a specialized separate cancer center (32.1%).
The most common specialty was breast cancer (60.6%), followed by gastrointestinal cancer (10.1%), urogenital cancer (9.2%), and lung cancer (8.3%).
Impact on treatment
The treatment modalities affected by the pandemic – through cancellations or delays in more than 10% of patients – included surgery (in 34% of centers), chemotherapy (22%), radiotherapy (13.7%), checkpoint inhibitor therapy (9.1%), monoclonal antibodies (9%), and oral targeted therapy (3.7%).
Among oncologists treating breast cancer, cancellations/delays in more than 10% of patients were reported for everolimus (18%), CDK4/6 inhibitors (8.9%), and endocrine therapy (2.2%).
Overall, 34.8% of respondents reported increased use of granulocyte colony–stimulating factor, and 6.4% reported increased use of erythropoietin.
On the other hand, 11.1% of respondents reported a decrease in the use of double immunotherapy, and 21.9% reported decreased use of corticosteroids.
Not only can the immunosuppressive effects of steroid use increase infection risks, Dr. Jerusalem noted, fever suppression can lead to a delayed diagnosis of COVID-19.
“To circumvent potential higher infection risks or greater disease severity, we use lower doses of steroids, but this is not based on studies,” he said.
“Previous exposure to steroids or being on steroids at the time of COVID-19 infection is a detrimental factor for complications and mortality,” commented ESMO President Solange Peters, MD, PhD, of Centre Hospitalier Universitaire Vaudois in Lausanne, Switzerland.
Dr. Peters noted that the observation was based on lung cancer registry findings. Furthermore, because data from smaller outbreaks of other coronavirus infections suggested worse prognosis and increased mortality, steroid use was already feared in the very early days of the COVID-19 pandemic.
Lastly, earlier cessation of palliative treatment was observed in 32.1% of centers, and 64.2% of respondents agreed that undertreatment because of COVID-19 is a major concern.
Dr. Jerusalem noted that the survey data do not explain the early cessation of palliative treatment. “I suspect that many patients died at home rather than alone in institutions because it was the only way they could die with their families around them.”
Telehealth, meetings, and trials
The survey also revealed rationales for the use of teleconsultation, including follow-up (94.5%), oral therapy (92.7%), immunotherapy (57.8%), and chemotherapy (55%).
Most respondents reported more frequent use of virtual meetings for continuing medical education (94%), oncologic team meetings (92%), and tumor boards (82%).
While about 82% of respondents said they were likely to continue the use of telemedicine, 45% said virtual conferences are not an acceptable alternative to live international conferences such as ESMO, Dr. Jerusalem said.
Finally, nearly three-quarters of respondents (72.5%) said all clinical trial activities are or will soon be activated, or never stopped, at their centers. On the other hand, 27.5% of respondents reported that their centers had major protocol violations or deviations, and 37% of respondents said they expect significant reductions in clinical trial activities this year.
Dr. Jerusalem concluded that COVID-19 is having a major, long-term impact on the organization of patient care, caregivers, continued medical education, and clinical trial activities in oncology.
He cautioned that “the risk of a delayed diagnosis of new cancers and economic consequences of COVID-19 on access to health care and cancer treatments have to be carefully evaluated.”
This research was funded by Fondation Léon Fredericq. Dr. Jerusalem disclosed relationships with Novartis, Roche, Lilly, Pfizer, Amgen, Bristol-Myers Squibb, AstraZeneca, Daiichi Sankyo, AbbVie, MedImmune, and Merck. Dr. Peters disclosed relationships with AbbVie, Amgen, AstraZeneca, and many other companies.
SOURCE: Jerusalem G et al. ESMO 2020, Abstract LBA76.
An international survey provides new insights into how COVID-19 has affected, and may continue to affect, the field of oncology.
The survey showed that “COVID-19 has had a major impact on the organization of patient care, on the well-being of caregivers, on continued medical education, and on clinical trial activities in oncology,” stated Guy Jerusalem, MD, PhD, of Centre Hospitalier Universitaire de Liège (Belgium).
Dr. Jerusalem presented these findings at the European Society for Medical Oncology Virtual Congress 2020.
The survey was distributed by 20 oncologists from 10 of the countries most affected by COVID-19. Responses were obtained from 109 oncologists representing centers in 18 countries. The responses were recorded between June 17 and July 14, 2020.
The survey consisted of 95 items intended to evaluate the impact of COVID-19 on the organization of oncologic care. Questions encompassed the capacity and service offered at each center, the magnitude of COVID-19–based care interruptions and the reasons for them, the ensuing challenges faced, interventions implemented, and the estimated harms to patients during the pandemic.
The 109 oncologists surveyed had a median of 20 years of oncology experience. A majority of respondents were men (61.5%), and the median age was 48.5 years.
The respondents had worked predominantly (62.4%) at academic hospitals, with 29.6% at community hospitals. Most respondents worked at general hospitals with an oncology unit (66.1%) rather than a specialized separate cancer center (32.1%).
The most common specialty was breast cancer (60.6%), followed by gastrointestinal cancer (10.1%), urogenital cancer (9.2%), and lung cancer (8.3%).
Impact on treatment
The treatment modalities affected by the pandemic – through cancellations or delays in more than 10% of patients – included surgery (in 34% of centers), chemotherapy (22%), radiotherapy (13.7%), checkpoint inhibitor therapy (9.1%), monoclonal antibodies (9%), and oral targeted therapy (3.7%).
Among oncologists treating breast cancer, cancellations/delays in more than 10% of patients were reported for everolimus (18%), CDK4/6 inhibitors (8.9%), and endocrine therapy (2.2%).
Overall, 34.8% of respondents reported increased use of granulocyte colony–stimulating factor, and 6.4% reported increased use of erythropoietin.
On the other hand, 11.1% of respondents reported a decrease in the use of double immunotherapy, and 21.9% reported decreased use of corticosteroids.
Not only can the immunosuppressive effects of steroid use increase infection risks, Dr. Jerusalem noted, fever suppression can lead to a delayed diagnosis of COVID-19.
“To circumvent potential higher infection risks or greater disease severity, we use lower doses of steroids, but this is not based on studies,” he said.
“Previous exposure to steroids or being on steroids at the time of COVID-19 infection is a detrimental factor for complications and mortality,” commented ESMO President Solange Peters, MD, PhD, of Centre Hospitalier Universitaire Vaudois in Lausanne, Switzerland.
Dr. Peters noted that the observation was based on lung cancer registry findings. Furthermore, because data from smaller outbreaks of other coronavirus infections suggested worse prognosis and increased mortality, steroid use was already feared in the very early days of the COVID-19 pandemic.
Lastly, earlier cessation of palliative treatment was observed in 32.1% of centers, and 64.2% of respondents agreed that undertreatment because of COVID-19 is a major concern.
Dr. Jerusalem noted that the survey data do not explain the early cessation of palliative treatment. “I suspect that many patients died at home rather than alone in institutions because it was the only way they could die with their families around them.”
Telehealth, meetings, and trials
The survey also revealed rationales for the use of teleconsultation, including follow-up (94.5%), oral therapy (92.7%), immunotherapy (57.8%), and chemotherapy (55%).
Most respondents reported more frequent use of virtual meetings for continuing medical education (94%), oncologic team meetings (92%), and tumor boards (82%).
While about 82% of respondents said they were likely to continue the use of telemedicine, 45% said virtual conferences are not an acceptable alternative to live international conferences such as ESMO, Dr. Jerusalem said.
Finally, nearly three-quarters of respondents (72.5%) said all clinical trial activities are or will soon be activated, or never stopped, at their centers. On the other hand, 27.5% of respondents reported that their centers had major protocol violations or deviations, and 37% of respondents said they expect significant reductions in clinical trial activities this year.
Dr. Jerusalem concluded that COVID-19 is having a major, long-term impact on the organization of patient care, caregivers, continued medical education, and clinical trial activities in oncology.
He cautioned that “the risk of a delayed diagnosis of new cancers and economic consequences of COVID-19 on access to health care and cancer treatments have to be carefully evaluated.”
This research was funded by Fondation Léon Fredericq. Dr. Jerusalem disclosed relationships with Novartis, Roche, Lilly, Pfizer, Amgen, Bristol-Myers Squibb, AstraZeneca, Daiichi Sankyo, AbbVie, MedImmune, and Merck. Dr. Peters disclosed relationships with AbbVie, Amgen, AstraZeneca, and many other companies.
SOURCE: Jerusalem G et al. ESMO 2020, Abstract LBA76.
FROM ESMO 2020
TKI choice key for fit/unfit patients with Ph+ALL
Adding tyrosine kinase inhibitors to the treatment of patients with Philadelphia chromosome–positive acute lymphoblastic leukemia (Ph+ALL) has significantly improved outcomes in recent years, but it’s still unclear which patients will also benefit from bone marrow transplants, and whether chemotherapy will gradually fade into the therapeutic background, a leukemia researcher contended.
said Anjali S. Advani, MD, of the Cleveland Clinic Taussig Cancer Institute.
Dr. Advani discussed her approach to treating both fit and frail patients with Ph+ALL during the virtual American Society of Hematology (ASH) Meeting on Hematologic Malignancies.
Increasing understanding of the importance of eliminating minimal residual disease (MRD) colors decisions about the best TKI to use in the first line.
“In terms of which TKI to use in the upfront setting, no randomized study has been done, but since MRD is associated with improved response, we often use this data to make a decision,” she said. “This, however, is complicated, because TKIs are combined with chemotherapy, there are many new TKIs, and finally, although we can start with one TKI, we can change to another TKI if we see that a patient is not responding appropriately.”
With the use of second-generation TKIs in combination with chemotherapy, rates of complete molecular remission (CMR) and major molecular remission (MMR) improved significantly over those seen with the first-in-class agent imatinib.
Notably, she said, the combination of ponatinib (Iclusig) with steroids as frontline therapy for elderly or frail patients with Ph+ALL was associated with a 60.5% CMR at week 24 in a phase 2 Italian trial (Blood 2017;130[Suppl. 1]:99).
Combining ponatinib with the hyper-CVAD regimen (cyclophosphamide, vincristine, doxorubicin, dexamethasone) improved the 3-month CMR rate to 74% and, the MMR rate to 15% (Lancet Haematol Dec. 2018 Dec 1;5[12]:e618-e627).
A 2016 propensity-score analysis comparing hyper-CVAD plus ponatinib with the hyper-CVAD plus dasatinib showed significantly better event-free survival (P = .035) and overall survival (P = .025) with the ponatinib-containing combination (Cancer 2016;122[23]:3650-6).
As with all potent regimens, however, the combination of hyper-CVAD and ponatinib is associated with relatively high percentages of grade 3 or greater nonhematologic toxicities, including transaminase and bilirubin elevation, pancreatitis, hypertension, venous thromboembolic events and arterial cardiovascular events.
Transplants in the TKI era
Prior to the advent of TKIs, there was strong evidence of the benefit of allogeneic stem cell transplant in patients with Ph+ALL in first remission (BMT 2003;31:623-32).
“The question is, now that we use TKIs, should we be transplanting patients still?” Dr. Advani said.
In the U.S. intergroup S0805 study looking at the combination of dasatinib and chemotherapy, there were distinct relapse-free and overall survival benefits for patients who underwent transplant. This trial did not evaluate MRD, however, ”so what we don’t know is for those patients achieving a complete molecular remission, would those patients do okay without transplant?” she said.
The current standard of care at Cleveland Clinic is to transplant eligible patients in first remission, ”but I think that’s likely to change as we get more data from these trials.”
In the COG AALL0031 trial of imatinib and chemotherapy in children with Ph+ALL, there was no significant benefit to stem cell transplant (Leukemia 2014 Jan 20;28:1467-71), Dr. Advani noted.
Other prognostic features associated with poor risk, such as 1KZF1 mutations with CDKN2A and/or PAX5 deletions, have been suggested as indicators for transplant, but “what’s less clear is what the impact of these abnormalities is now with the second- and third-generation TKIs, and also whether these various abnormalities correlate with molecular responses or achievement of complete molecular remission,” she said.
Frail/unfit patients
Therapeutic options for frail or unfit patients include the combination of dasatinib and prednisone, which was associated in one study with a 93% complete hematologic remission rate by day 22, and at 20 months with a 69.2% overall survival rate, and 51.1% disease-free survival rate.(Blood. 2011;118[25]:6521-8).
In this study MRD correlated with disease-free survival, but 23 of 53 patients experienced relapse, and 12 patients with relapsed disease had the T3151 mutation. Ponatinib would be a second-line option for this latter group of patients, Dr. Advani said.
A study reported at the 2017 ASH annual meeting looked at the combination of ponatinib with steroids in patients either 60 and older or younger unfit patients with Ph+ALL.
The primary endpoint of complete hematological response at 24 weeks in at least 75% of patients was reached early, with 40 of 42 patients (95.2%) having a complete hematologic response after 1 course of therapy (6 weeks). The CMR rate at 24 weeks was 61%, and 1-year overall survival was 87.5%.
There were 13 serious adverse events related to ponatinib, however, including one death, and one patient who experienced a relapse was found to have the T315L ponatinib-resistance mutation. (Blood 2017 Dec. 7;130[Suppl. 1]:99).
“I think a few things with ponatinib and steroids that we still don’t know are the long-term follow-up results of this as a single agent in combination with steroids, and second, in this elderly population, if you look, patients are dropping out due to adverse events and toxicities,” she said.
TKIs plus antibodies
The S1318 trial conducted by the SWOG cancer research network contains both a Ph+ALL and a Ph-negative ALL cohort. In this trial, patients with Ph+ALL receive dasatinib and steroids as induction, then go on to receive blinatumomab (Blincyto) with dasatinib for three cycles, followed by maintenance therapy with dasitinib and prednisone.
A trial currently in the planning stages, EA9181, will compare in a randomized fashion induction regimens with either dasatinib or ponatinib at the investigator’s discretion with steroids and either blinatumomab or chemotherapy.
No funding source was reported for the presentation. Dr. Advani disclosed steering committee activities, honoraria/consulting, and research funding from multiple companies.
Adding tyrosine kinase inhibitors to the treatment of patients with Philadelphia chromosome–positive acute lymphoblastic leukemia (Ph+ALL) has significantly improved outcomes in recent years, but it’s still unclear which patients will also benefit from bone marrow transplants, and whether chemotherapy will gradually fade into the therapeutic background, a leukemia researcher contended.
said Anjali S. Advani, MD, of the Cleveland Clinic Taussig Cancer Institute.
Dr. Advani discussed her approach to treating both fit and frail patients with Ph+ALL during the virtual American Society of Hematology (ASH) Meeting on Hematologic Malignancies.
Increasing understanding of the importance of eliminating minimal residual disease (MRD) colors decisions about the best TKI to use in the first line.
“In terms of which TKI to use in the upfront setting, no randomized study has been done, but since MRD is associated with improved response, we often use this data to make a decision,” she said. “This, however, is complicated, because TKIs are combined with chemotherapy, there are many new TKIs, and finally, although we can start with one TKI, we can change to another TKI if we see that a patient is not responding appropriately.”
With the use of second-generation TKIs in combination with chemotherapy, rates of complete molecular remission (CMR) and major molecular remission (MMR) improved significantly over those seen with the first-in-class agent imatinib.
Notably, she said, the combination of ponatinib (Iclusig) with steroids as frontline therapy for elderly or frail patients with Ph+ALL was associated with a 60.5% CMR at week 24 in a phase 2 Italian trial (Blood 2017;130[Suppl. 1]:99).
Combining ponatinib with the hyper-CVAD regimen (cyclophosphamide, vincristine, doxorubicin, dexamethasone) improved the 3-month CMR rate to 74% and, the MMR rate to 15% (Lancet Haematol Dec. 2018 Dec 1;5[12]:e618-e627).
A 2016 propensity-score analysis comparing hyper-CVAD plus ponatinib with the hyper-CVAD plus dasatinib showed significantly better event-free survival (P = .035) and overall survival (P = .025) with the ponatinib-containing combination (Cancer 2016;122[23]:3650-6).
As with all potent regimens, however, the combination of hyper-CVAD and ponatinib is associated with relatively high percentages of grade 3 or greater nonhematologic toxicities, including transaminase and bilirubin elevation, pancreatitis, hypertension, venous thromboembolic events and arterial cardiovascular events.
Transplants in the TKI era
Prior to the advent of TKIs, there was strong evidence of the benefit of allogeneic stem cell transplant in patients with Ph+ALL in first remission (BMT 2003;31:623-32).
“The question is, now that we use TKIs, should we be transplanting patients still?” Dr. Advani said.
In the U.S. intergroup S0805 study looking at the combination of dasatinib and chemotherapy, there were distinct relapse-free and overall survival benefits for patients who underwent transplant. This trial did not evaluate MRD, however, ”so what we don’t know is for those patients achieving a complete molecular remission, would those patients do okay without transplant?” she said.
The current standard of care at Cleveland Clinic is to transplant eligible patients in first remission, ”but I think that’s likely to change as we get more data from these trials.”
In the COG AALL0031 trial of imatinib and chemotherapy in children with Ph+ALL, there was no significant benefit to stem cell transplant (Leukemia 2014 Jan 20;28:1467-71), Dr. Advani noted.
Other prognostic features associated with poor risk, such as 1KZF1 mutations with CDKN2A and/or PAX5 deletions, have been suggested as indicators for transplant, but “what’s less clear is what the impact of these abnormalities is now with the second- and third-generation TKIs, and also whether these various abnormalities correlate with molecular responses or achievement of complete molecular remission,” she said.
Frail/unfit patients
Therapeutic options for frail or unfit patients include the combination of dasatinib and prednisone, which was associated in one study with a 93% complete hematologic remission rate by day 22, and at 20 months with a 69.2% overall survival rate, and 51.1% disease-free survival rate.(Blood. 2011;118[25]:6521-8).
In this study MRD correlated with disease-free survival, but 23 of 53 patients experienced relapse, and 12 patients with relapsed disease had the T3151 mutation. Ponatinib would be a second-line option for this latter group of patients, Dr. Advani said.
A study reported at the 2017 ASH annual meeting looked at the combination of ponatinib with steroids in patients either 60 and older or younger unfit patients with Ph+ALL.
The primary endpoint of complete hematological response at 24 weeks in at least 75% of patients was reached early, with 40 of 42 patients (95.2%) having a complete hematologic response after 1 course of therapy (6 weeks). The CMR rate at 24 weeks was 61%, and 1-year overall survival was 87.5%.
There were 13 serious adverse events related to ponatinib, however, including one death, and one patient who experienced a relapse was found to have the T315L ponatinib-resistance mutation. (Blood 2017 Dec. 7;130[Suppl. 1]:99).
“I think a few things with ponatinib and steroids that we still don’t know are the long-term follow-up results of this as a single agent in combination with steroids, and second, in this elderly population, if you look, patients are dropping out due to adverse events and toxicities,” she said.
TKIs plus antibodies
The S1318 trial conducted by the SWOG cancer research network contains both a Ph+ALL and a Ph-negative ALL cohort. In this trial, patients with Ph+ALL receive dasatinib and steroids as induction, then go on to receive blinatumomab (Blincyto) with dasatinib for three cycles, followed by maintenance therapy with dasitinib and prednisone.
A trial currently in the planning stages, EA9181, will compare in a randomized fashion induction regimens with either dasatinib or ponatinib at the investigator’s discretion with steroids and either blinatumomab or chemotherapy.
No funding source was reported for the presentation. Dr. Advani disclosed steering committee activities, honoraria/consulting, and research funding from multiple companies.
Adding tyrosine kinase inhibitors to the treatment of patients with Philadelphia chromosome–positive acute lymphoblastic leukemia (Ph+ALL) has significantly improved outcomes in recent years, but it’s still unclear which patients will also benefit from bone marrow transplants, and whether chemotherapy will gradually fade into the therapeutic background, a leukemia researcher contended.
said Anjali S. Advani, MD, of the Cleveland Clinic Taussig Cancer Institute.
Dr. Advani discussed her approach to treating both fit and frail patients with Ph+ALL during the virtual American Society of Hematology (ASH) Meeting on Hematologic Malignancies.
Increasing understanding of the importance of eliminating minimal residual disease (MRD) colors decisions about the best TKI to use in the first line.
“In terms of which TKI to use in the upfront setting, no randomized study has been done, but since MRD is associated with improved response, we often use this data to make a decision,” she said. “This, however, is complicated, because TKIs are combined with chemotherapy, there are many new TKIs, and finally, although we can start with one TKI, we can change to another TKI if we see that a patient is not responding appropriately.”
With the use of second-generation TKIs in combination with chemotherapy, rates of complete molecular remission (CMR) and major molecular remission (MMR) improved significantly over those seen with the first-in-class agent imatinib.
Notably, she said, the combination of ponatinib (Iclusig) with steroids as frontline therapy for elderly or frail patients with Ph+ALL was associated with a 60.5% CMR at week 24 in a phase 2 Italian trial (Blood 2017;130[Suppl. 1]:99).
Combining ponatinib with the hyper-CVAD regimen (cyclophosphamide, vincristine, doxorubicin, dexamethasone) improved the 3-month CMR rate to 74% and, the MMR rate to 15% (Lancet Haematol Dec. 2018 Dec 1;5[12]:e618-e627).
A 2016 propensity-score analysis comparing hyper-CVAD plus ponatinib with the hyper-CVAD plus dasatinib showed significantly better event-free survival (P = .035) and overall survival (P = .025) with the ponatinib-containing combination (Cancer 2016;122[23]:3650-6).
As with all potent regimens, however, the combination of hyper-CVAD and ponatinib is associated with relatively high percentages of grade 3 or greater nonhematologic toxicities, including transaminase and bilirubin elevation, pancreatitis, hypertension, venous thromboembolic events and arterial cardiovascular events.
Transplants in the TKI era
Prior to the advent of TKIs, there was strong evidence of the benefit of allogeneic stem cell transplant in patients with Ph+ALL in first remission (BMT 2003;31:623-32).
“The question is, now that we use TKIs, should we be transplanting patients still?” Dr. Advani said.
In the U.S. intergroup S0805 study looking at the combination of dasatinib and chemotherapy, there were distinct relapse-free and overall survival benefits for patients who underwent transplant. This trial did not evaluate MRD, however, ”so what we don’t know is for those patients achieving a complete molecular remission, would those patients do okay without transplant?” she said.
The current standard of care at Cleveland Clinic is to transplant eligible patients in first remission, ”but I think that’s likely to change as we get more data from these trials.”
In the COG AALL0031 trial of imatinib and chemotherapy in children with Ph+ALL, there was no significant benefit to stem cell transplant (Leukemia 2014 Jan 20;28:1467-71), Dr. Advani noted.
Other prognostic features associated with poor risk, such as 1KZF1 mutations with CDKN2A and/or PAX5 deletions, have been suggested as indicators for transplant, but “what’s less clear is what the impact of these abnormalities is now with the second- and third-generation TKIs, and also whether these various abnormalities correlate with molecular responses or achievement of complete molecular remission,” she said.
Frail/unfit patients
Therapeutic options for frail or unfit patients include the combination of dasatinib and prednisone, which was associated in one study with a 93% complete hematologic remission rate by day 22, and at 20 months with a 69.2% overall survival rate, and 51.1% disease-free survival rate.(Blood. 2011;118[25]:6521-8).
In this study MRD correlated with disease-free survival, but 23 of 53 patients experienced relapse, and 12 patients with relapsed disease had the T3151 mutation. Ponatinib would be a second-line option for this latter group of patients, Dr. Advani said.
A study reported at the 2017 ASH annual meeting looked at the combination of ponatinib with steroids in patients either 60 and older or younger unfit patients with Ph+ALL.
The primary endpoint of complete hematological response at 24 weeks in at least 75% of patients was reached early, with 40 of 42 patients (95.2%) having a complete hematologic response after 1 course of therapy (6 weeks). The CMR rate at 24 weeks was 61%, and 1-year overall survival was 87.5%.
There were 13 serious adverse events related to ponatinib, however, including one death, and one patient who experienced a relapse was found to have the T315L ponatinib-resistance mutation. (Blood 2017 Dec. 7;130[Suppl. 1]:99).
“I think a few things with ponatinib and steroids that we still don’t know are the long-term follow-up results of this as a single agent in combination with steroids, and second, in this elderly population, if you look, patients are dropping out due to adverse events and toxicities,” she said.
TKIs plus antibodies
The S1318 trial conducted by the SWOG cancer research network contains both a Ph+ALL and a Ph-negative ALL cohort. In this trial, patients with Ph+ALL receive dasatinib and steroids as induction, then go on to receive blinatumomab (Blincyto) with dasatinib for three cycles, followed by maintenance therapy with dasitinib and prednisone.
A trial currently in the planning stages, EA9181, will compare in a randomized fashion induction regimens with either dasatinib or ponatinib at the investigator’s discretion with steroids and either blinatumomab or chemotherapy.
No funding source was reported for the presentation. Dr. Advani disclosed steering committee activities, honoraria/consulting, and research funding from multiple companies.
FROM ASH HEMATOLOGIC MALIGNANCIES 2020
CSF metabolomic profile linked to cancer-related fatigue in children with ALL
Children and adolescents with cancer report significantly more fatigue than their counterparts without cancer, and cancer-related fatigue (CRF) is “one of the most prevalent and distressing symptoms reported during childhood cancer therapy,” according to Austin L. Brown, PhD, and his colleagues.
Cerebrospinal fluid (CSF) profiles suggest three metabolites are significantly associated with CRF in children with acute lymphoblastic leukemia (ALL), according to a report published in the Journal of Pain and Symptom Management.
The researchers assessed the clinical and demographic characteristics of 171 pediatric ALL patients, who were divided into discovery (n = 86) and replication (n = 85) cohorts.
The entire population had a mean age at diagnosis of 8.48 years; was 56.1% male; and 85.4% had B-lineage ALL. A total of 63.7% received high- or very-high-risk treatment.
CSF samples were obtained and subjected to metabolomic analysis, according to Dr. Brown, an assistant professor at the Baylor College of Medicine, Houston, and colleagues.
The researchers analyzed postinduction CSF from the aforementioned 171 patients as well as diagnostic CSF from 48 patients in an additional replication cohort.
Significant metabolites
Analysis of postinduction CSF showed that three metabolites were significantly associated with fatigue in both the discovery and replication cohorts, comprising gamma-glutamylglutamine, dimethylglycine, and asparagine (P < .05).
In diagnostic CSF samples, the abundance of gamma-glutamylglutamine was significantly associated with fatigue (P =.0062).
The metabolites have been implicated in neurotransmitter transportation and glutathione recycling, suggesting glutamatergic pathways or oxidative stress may contribute to ALL-associated CRF, according to the researchers.
“Ultimately, this line of investigation may aid in the development of new prevention and treatment approaches informed by an improved understanding of the etiology and risk factors for cancer-related fatigue,” the researchers concluded.
The study was sponsored by the National Cancer Institute and several nonprofit organizations. The authors reported that they had no conflicts of interest.
SOURCE: Brown AL et al. J Pain Symptom Manage. 2020 Sep 1. doi: 10.1016/j.jpainsymman.2020.08.030.
Children and adolescents with cancer report significantly more fatigue than their counterparts without cancer, and cancer-related fatigue (CRF) is “one of the most prevalent and distressing symptoms reported during childhood cancer therapy,” according to Austin L. Brown, PhD, and his colleagues.
Cerebrospinal fluid (CSF) profiles suggest three metabolites are significantly associated with CRF in children with acute lymphoblastic leukemia (ALL), according to a report published in the Journal of Pain and Symptom Management.
The researchers assessed the clinical and demographic characteristics of 171 pediatric ALL patients, who were divided into discovery (n = 86) and replication (n = 85) cohorts.
The entire population had a mean age at diagnosis of 8.48 years; was 56.1% male; and 85.4% had B-lineage ALL. A total of 63.7% received high- or very-high-risk treatment.
CSF samples were obtained and subjected to metabolomic analysis, according to Dr. Brown, an assistant professor at the Baylor College of Medicine, Houston, and colleagues.
The researchers analyzed postinduction CSF from the aforementioned 171 patients as well as diagnostic CSF from 48 patients in an additional replication cohort.
Significant metabolites
Analysis of postinduction CSF showed that three metabolites were significantly associated with fatigue in both the discovery and replication cohorts, comprising gamma-glutamylglutamine, dimethylglycine, and asparagine (P < .05).
In diagnostic CSF samples, the abundance of gamma-glutamylglutamine was significantly associated with fatigue (P =.0062).
The metabolites have been implicated in neurotransmitter transportation and glutathione recycling, suggesting glutamatergic pathways or oxidative stress may contribute to ALL-associated CRF, according to the researchers.
“Ultimately, this line of investigation may aid in the development of new prevention and treatment approaches informed by an improved understanding of the etiology and risk factors for cancer-related fatigue,” the researchers concluded.
The study was sponsored by the National Cancer Institute and several nonprofit organizations. The authors reported that they had no conflicts of interest.
SOURCE: Brown AL et al. J Pain Symptom Manage. 2020 Sep 1. doi: 10.1016/j.jpainsymman.2020.08.030.
Children and adolescents with cancer report significantly more fatigue than their counterparts without cancer, and cancer-related fatigue (CRF) is “one of the most prevalent and distressing symptoms reported during childhood cancer therapy,” according to Austin L. Brown, PhD, and his colleagues.
Cerebrospinal fluid (CSF) profiles suggest three metabolites are significantly associated with CRF in children with acute lymphoblastic leukemia (ALL), according to a report published in the Journal of Pain and Symptom Management.
The researchers assessed the clinical and demographic characteristics of 171 pediatric ALL patients, who were divided into discovery (n = 86) and replication (n = 85) cohorts.
The entire population had a mean age at diagnosis of 8.48 years; was 56.1% male; and 85.4% had B-lineage ALL. A total of 63.7% received high- or very-high-risk treatment.
CSF samples were obtained and subjected to metabolomic analysis, according to Dr. Brown, an assistant professor at the Baylor College of Medicine, Houston, and colleagues.
The researchers analyzed postinduction CSF from the aforementioned 171 patients as well as diagnostic CSF from 48 patients in an additional replication cohort.
Significant metabolites
Analysis of postinduction CSF showed that three metabolites were significantly associated with fatigue in both the discovery and replication cohorts, comprising gamma-glutamylglutamine, dimethylglycine, and asparagine (P < .05).
In diagnostic CSF samples, the abundance of gamma-glutamylglutamine was significantly associated with fatigue (P =.0062).
The metabolites have been implicated in neurotransmitter transportation and glutathione recycling, suggesting glutamatergic pathways or oxidative stress may contribute to ALL-associated CRF, according to the researchers.
“Ultimately, this line of investigation may aid in the development of new prevention and treatment approaches informed by an improved understanding of the etiology and risk factors for cancer-related fatigue,” the researchers concluded.
The study was sponsored by the National Cancer Institute and several nonprofit organizations. The authors reported that they had no conflicts of interest.
SOURCE: Brown AL et al. J Pain Symptom Manage. 2020 Sep 1. doi: 10.1016/j.jpainsymman.2020.08.030.
FROM THE JOURNAL OF PAIN AND SYMPTOM MANAGEMENT
Polygenic risk score may predict VTE in adolescents, but not adults, with ALL
Although patients with acute lymphoblastic leukemia (ALL) are at known risk of venous thromboembolism (VTE), there was no overall genetic correlation found to be associated with that susceptibility in the overall population. However, a significant genetic predisposition to VTE was found in adolescent ALL patients, according to a report published in Thrombosis Research.
The researchers assessed the prospectively registered VTE events and collected germline DNA in patients aged 1-45.9 years in the Nordic Society of Pediatric Hematology and Oncology (NOPHO) ALL2008 study, which took place from 2008 to 2016. The researchers performed polygenic risk score (PRS) analysis on VTE development in the NOPHO cohort, according to Kirsten Brunsvig Jarvis, MD, of Oslo University Hospital, and colleagues.
The researchers used summary statistics from two large genomewide association studies on VTE in adults (the International Network of Venous Thromboembolism Clinical Research Networks [INVENT] consortium and the UK Biobank).
Of 1,252 patients with ALL in the genetic cohort, 89 developed VTE (2.5-year cumulative incidence, 7.2%; 95% confidence interval,5.7-8.6) at a median 12.7 weeks from diagnosis.
Overall, an analysis of single-nucleotide polymorphisms (SNPs) from INVENT and UK Biobank studies did not reveal evidence of polygenic correlation with VTE in patients with ALL, the researchers reported. However, when separating adolescents aged 10.0-17.9 years (n = 231) from adults aged 18 years or older (n = 127), they saw polygenic overlap between the INVENT study and thromboembolism development in the adolescent population.
The best-fit polygenic risk score, including 16,144 SNPs, was associated with VTE in adolescents with ALL at a hazard ratio of 1.76 (95% CI, 1.23-2.52; P = .02).
Adolescent vs. adult risk
The researchers expressed surprise that they did not find evidence of genetic overlap in adults. But they stated that, in general, VTE occurs more frequently in adults as part of natural aging, while children and adolescents are physiologically protected. This might explain why genetics might play a stronger role in the high-risk situation of cancer and chemotherapy in adolescents who do not have as many additional exogenic risk factors as adults.
“The usefulness of genetic studies on [V]TE in the general adult population is limited when it comes to understanding the etiology of [V]TE in patients with ALL. However, we found evidence of polygenic overlap in subgroup analysis of adolescents aged 10.0-17.9 years with ALL, and we believe the genetics of [V]TE in this group should be further explored in future risk prediction models for identification of those who might benefit from thromboprophylaxis,” the researchers concluded.
The study was supported by research grant from the South-Eastern Norway Regional Health Authority. The authors reported that they had no conflicts of interest.
SOURCE: Jarvis KB et al. Thromb Res. 2020 Aug 11.doi: 10.1016/j.thromres.2020.08.015.
Although patients with acute lymphoblastic leukemia (ALL) are at known risk of venous thromboembolism (VTE), there was no overall genetic correlation found to be associated with that susceptibility in the overall population. However, a significant genetic predisposition to VTE was found in adolescent ALL patients, according to a report published in Thrombosis Research.
The researchers assessed the prospectively registered VTE events and collected germline DNA in patients aged 1-45.9 years in the Nordic Society of Pediatric Hematology and Oncology (NOPHO) ALL2008 study, which took place from 2008 to 2016. The researchers performed polygenic risk score (PRS) analysis on VTE development in the NOPHO cohort, according to Kirsten Brunsvig Jarvis, MD, of Oslo University Hospital, and colleagues.
The researchers used summary statistics from two large genomewide association studies on VTE in adults (the International Network of Venous Thromboembolism Clinical Research Networks [INVENT] consortium and the UK Biobank).
Of 1,252 patients with ALL in the genetic cohort, 89 developed VTE (2.5-year cumulative incidence, 7.2%; 95% confidence interval,5.7-8.6) at a median 12.7 weeks from diagnosis.
Overall, an analysis of single-nucleotide polymorphisms (SNPs) from INVENT and UK Biobank studies did not reveal evidence of polygenic correlation with VTE in patients with ALL, the researchers reported. However, when separating adolescents aged 10.0-17.9 years (n = 231) from adults aged 18 years or older (n = 127), they saw polygenic overlap between the INVENT study and thromboembolism development in the adolescent population.
The best-fit polygenic risk score, including 16,144 SNPs, was associated with VTE in adolescents with ALL at a hazard ratio of 1.76 (95% CI, 1.23-2.52; P = .02).
Adolescent vs. adult risk
The researchers expressed surprise that they did not find evidence of genetic overlap in adults. But they stated that, in general, VTE occurs more frequently in adults as part of natural aging, while children and adolescents are physiologically protected. This might explain why genetics might play a stronger role in the high-risk situation of cancer and chemotherapy in adolescents who do not have as many additional exogenic risk factors as adults.
“The usefulness of genetic studies on [V]TE in the general adult population is limited when it comes to understanding the etiology of [V]TE in patients with ALL. However, we found evidence of polygenic overlap in subgroup analysis of adolescents aged 10.0-17.9 years with ALL, and we believe the genetics of [V]TE in this group should be further explored in future risk prediction models for identification of those who might benefit from thromboprophylaxis,” the researchers concluded.
The study was supported by research grant from the South-Eastern Norway Regional Health Authority. The authors reported that they had no conflicts of interest.
SOURCE: Jarvis KB et al. Thromb Res. 2020 Aug 11.doi: 10.1016/j.thromres.2020.08.015.
Although patients with acute lymphoblastic leukemia (ALL) are at known risk of venous thromboembolism (VTE), there was no overall genetic correlation found to be associated with that susceptibility in the overall population. However, a significant genetic predisposition to VTE was found in adolescent ALL patients, according to a report published in Thrombosis Research.
The researchers assessed the prospectively registered VTE events and collected germline DNA in patients aged 1-45.9 years in the Nordic Society of Pediatric Hematology and Oncology (NOPHO) ALL2008 study, which took place from 2008 to 2016. The researchers performed polygenic risk score (PRS) analysis on VTE development in the NOPHO cohort, according to Kirsten Brunsvig Jarvis, MD, of Oslo University Hospital, and colleagues.
The researchers used summary statistics from two large genomewide association studies on VTE in adults (the International Network of Venous Thromboembolism Clinical Research Networks [INVENT] consortium and the UK Biobank).
Of 1,252 patients with ALL in the genetic cohort, 89 developed VTE (2.5-year cumulative incidence, 7.2%; 95% confidence interval,5.7-8.6) at a median 12.7 weeks from diagnosis.
Overall, an analysis of single-nucleotide polymorphisms (SNPs) from INVENT and UK Biobank studies did not reveal evidence of polygenic correlation with VTE in patients with ALL, the researchers reported. However, when separating adolescents aged 10.0-17.9 years (n = 231) from adults aged 18 years or older (n = 127), they saw polygenic overlap between the INVENT study and thromboembolism development in the adolescent population.
The best-fit polygenic risk score, including 16,144 SNPs, was associated with VTE in adolescents with ALL at a hazard ratio of 1.76 (95% CI, 1.23-2.52; P = .02).
Adolescent vs. adult risk
The researchers expressed surprise that they did not find evidence of genetic overlap in adults. But they stated that, in general, VTE occurs more frequently in adults as part of natural aging, while children and adolescents are physiologically protected. This might explain why genetics might play a stronger role in the high-risk situation of cancer and chemotherapy in adolescents who do not have as many additional exogenic risk factors as adults.
“The usefulness of genetic studies on [V]TE in the general adult population is limited when it comes to understanding the etiology of [V]TE in patients with ALL. However, we found evidence of polygenic overlap in subgroup analysis of adolescents aged 10.0-17.9 years with ALL, and we believe the genetics of [V]TE in this group should be further explored in future risk prediction models for identification of those who might benefit from thromboprophylaxis,” the researchers concluded.
The study was supported by research grant from the South-Eastern Norway Regional Health Authority. The authors reported that they had no conflicts of interest.
SOURCE: Jarvis KB et al. Thromb Res. 2020 Aug 11.doi: 10.1016/j.thromres.2020.08.015.
FROM THROMBOSIS RESEARCH
Posaconazole prophylaxis was effective in children with ALL undergoing chemotherapy
Targeted prophylaxis with posaconazole was more effective than fluconazole in children with acute lymphoblastic leukemia who were undergoing induction chemotherapy in order to prevent invasive fungal infection, according to a study by Tian Zhang of Xidian University, Xi’an, China, and colleagues.
The researchers performed a single-center, retrospective cohort study of 155 patients with newly diagnosed acute lymphoblastic leukemia, comparing invasive fungal infections in those who received no prophylaxis (60 patients), posaconazole prophylaxis (70), or fluconazole prophylaxis (55) during induction therapy, according to a report published in the Journal of Microbiology, Immunology and Infection.
Proven and probable invasive fungal infections occurred during the induction phase in 45% in the no-prophylaxis group, in 18% of the posaconazole group and in 72% of the fluconazole group. Posaconazole prophylaxis reduced the odds of invasive fungal infections by greater than 60%, prolonged infection-free survival significantly, and did not increase the risk of hepatotoxicity.
In addition, the researchers found that the combination of age at diagnosis, clinically documented bacterial infection in the first 15 days of induction therapy, and absolute neutrophil count curve enabled significant prediction of the susceptibility to infections after receiving posaconazole prophylaxis.
“In general, these findings may serve as a basis for developing screening protocols to identify children who are at high risk for infection despite posaconazole prophylaxis so that early intervention can be initiated to mitigate fungal infections,” the researchers concluded.
The authors reported that they had no conflicts of interest.
SOURCE: Zhang T et al. J Microbiol Immunol Infect. 2020 Aug 1. doi: 10.1016/j.jmii.2020.07.008.
Targeted prophylaxis with posaconazole was more effective than fluconazole in children with acute lymphoblastic leukemia who were undergoing induction chemotherapy in order to prevent invasive fungal infection, according to a study by Tian Zhang of Xidian University, Xi’an, China, and colleagues.
The researchers performed a single-center, retrospective cohort study of 155 patients with newly diagnosed acute lymphoblastic leukemia, comparing invasive fungal infections in those who received no prophylaxis (60 patients), posaconazole prophylaxis (70), or fluconazole prophylaxis (55) during induction therapy, according to a report published in the Journal of Microbiology, Immunology and Infection.
Proven and probable invasive fungal infections occurred during the induction phase in 45% in the no-prophylaxis group, in 18% of the posaconazole group and in 72% of the fluconazole group. Posaconazole prophylaxis reduced the odds of invasive fungal infections by greater than 60%, prolonged infection-free survival significantly, and did not increase the risk of hepatotoxicity.
In addition, the researchers found that the combination of age at diagnosis, clinically documented bacterial infection in the first 15 days of induction therapy, and absolute neutrophil count curve enabled significant prediction of the susceptibility to infections after receiving posaconazole prophylaxis.
“In general, these findings may serve as a basis for developing screening protocols to identify children who are at high risk for infection despite posaconazole prophylaxis so that early intervention can be initiated to mitigate fungal infections,” the researchers concluded.
The authors reported that they had no conflicts of interest.
SOURCE: Zhang T et al. J Microbiol Immunol Infect. 2020 Aug 1. doi: 10.1016/j.jmii.2020.07.008.
Targeted prophylaxis with posaconazole was more effective than fluconazole in children with acute lymphoblastic leukemia who were undergoing induction chemotherapy in order to prevent invasive fungal infection, according to a study by Tian Zhang of Xidian University, Xi’an, China, and colleagues.
The researchers performed a single-center, retrospective cohort study of 155 patients with newly diagnosed acute lymphoblastic leukemia, comparing invasive fungal infections in those who received no prophylaxis (60 patients), posaconazole prophylaxis (70), or fluconazole prophylaxis (55) during induction therapy, according to a report published in the Journal of Microbiology, Immunology and Infection.
Proven and probable invasive fungal infections occurred during the induction phase in 45% in the no-prophylaxis group, in 18% of the posaconazole group and in 72% of the fluconazole group. Posaconazole prophylaxis reduced the odds of invasive fungal infections by greater than 60%, prolonged infection-free survival significantly, and did not increase the risk of hepatotoxicity.
In addition, the researchers found that the combination of age at diagnosis, clinically documented bacterial infection in the first 15 days of induction therapy, and absolute neutrophil count curve enabled significant prediction of the susceptibility to infections after receiving posaconazole prophylaxis.
“In general, these findings may serve as a basis for developing screening protocols to identify children who are at high risk for infection despite posaconazole prophylaxis so that early intervention can be initiated to mitigate fungal infections,” the researchers concluded.
The authors reported that they had no conflicts of interest.
SOURCE: Zhang T et al. J Microbiol Immunol Infect. 2020 Aug 1. doi: 10.1016/j.jmii.2020.07.008.
FROM THE JOURNAL OF MICROBIOLOGY, IMMUNOLOGY AND INFECTION
Inotuzumab / bosutinib treat R/R Ph+ ALL, CML in blast phase
Patients with Philadelphia chromosome–positive acute lymphoblastic or chronic myeloid leukemias in lymphoid blast phase may have longer event-free and overall survival with a combination of inotuzumab ozogamicin (Besponsa) and bosutinib (Bosulif) than with standard chemotherapy combined with a targeted agent, investigators in a phase 1/2 study reported.
Among patients with relapsed or refractory Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) or chronic myeloid leukemia (Ph+ CML) in lymphoid blast phase treated with inotuzumab ozogamicin (Besponsa) and bosutinib (Bosulif), the median overall survival was 15.4 months. In contrast, median overall survival for similar patients treated with chemotherapy and a tyrosine kinase inhibitor (TKI) was less than 6 months, reported Nitin Jain, MD, and colleagues from the University of Texas MD Anderson Cancer Center in Houston.
The study was presented in a scientific poster session as part of the virtual annual congress of the European Hematology Association.
“Patients with relapsed/refractory Philadelphia chromosome–positive ALL/CML in lymphoid blast crisis are also best managed with a TKI targeting the constitutively active ABL kinase with the TKI selected based on presence of ABL kinase mutations and prior TKI history,” commented Marlise R. Luskin, MD, a leukemia specialist at the Dana-Farber Cancer Institute in Boston.
“A critical question for this patient population is whether these two approaches [TKI and inotuzumab ozogamicin] can be administered safely in combination. I congratulate MD Anderson for completion of this Phase I trial which demonstrates that inotuzumab and bosutinib can be safely combined with identification of a maximum tolerated dose of bosutinib 400 mg daily when administered in combination. I look forward to further studies that explore the efficacy of combination versus the approved single-agent regimen,” she said in an interview.
Study details
To see whether they could improve the dismal outcomes for patients with Ph+ ALL or Ph+ CML in lymphoid blast phase, they studied the combination of inotuzumab ozogamicin, an anti-CD22 monoclonal antibody conjugated to the cytotoxic antibiotic calicheamicin, and bosutinib, an inhibitor of the ABL kinase. Inotuzumab is approved in the United States for treatment of adults with relapsed or refractory B-cell precursor ALL, bosutinib is approved for the treatment of patients with newly-diagnosed chronic phase Ph+ CML and for adults with chronic, accelerated, or blast phase Ph+ CML with resistance or intolerance to prior therapy.
The investigators enrolled 16 patients with Ph+ ALL and 2 with Ph+ CML with bone marrow blasts greater than 5%, CD22 expressed on at least 20% of blasts, and good to fair performance status. The patients also had adequate organ function as measured by liver enzyme, total bilirubin, and serum creatinine levels. Patients with the T315I mutation, prior anti-CD22 therapy, active graft-versus-host disease, or liver disease were excluded.
The patients received inotuzumab 0.8 mg/m2 intravenously on day 1, they received 0.5 mg/m2 on days 8 and 15 of cycle 1, and they received 0.5 mg/m2 on days 1, 8, and 15 of cycles 2 through 6. Each cycle was 4 weeks. Patients who had a complete remission (CR), had complete cytogenetic remission (CCyR), or became negative for minimal residual disease (MRD) continued on 1 mg/m2 every 4 weeks. Bosutinib was dosed continuously day starting on the first day of cycle 1 and continued until disease progression or toxicity.
After a median follow-up of 36.7 months, 11 of the 18 patients had CRs, and 4 had CRs with incomplete recovery of hematologic counts. In addition, 13 of 16 patients with without diploid cytogenetics at the start of the study had CCyr; 14 patients had major molecular remission; 10 had complete molecular remission, and 11 were negative by flow cytometry.
As noted before, the median overall survival was 15.4 months. Event-free survival – time to lack of response, relapse, MRD relapse requiring therapy, or death – was 8 months. The event-free survival data were not censored for allogeneic stem cell transplant. Six patients underwent transplant while in remission.
The primary objective of the phase 1 trial was to evaluate safety of the combination and determine the maximum tolerated dose of bosutinib, which was determined to be 400 mg daily. At this dose level, one patient had a dose-limiting toxicity in the form of a grade 3 skin rash.
The most frequent adverse events were diarrhea and rash, in 50% of patients each, and nausea in 39% of patients. Grade 3 adverse events included were rash in three patients and reversible alanine aminotransferase and hyponatremia in one patient each. No patients developed veno-occlusive disease, and there no deaths within 30 days of the start of therapy.
Dr. Jain disclosed consultancy, honoraria, advisory board/committee activity, and research funding from Pfizer, maker of inotuzumab ozogamicin and bosutinib. Dr. Luskin reported no relevant disclosures.
SOURCE: Jain N et al. EHA25, Abstract EP396.
Patients with Philadelphia chromosome–positive acute lymphoblastic or chronic myeloid leukemias in lymphoid blast phase may have longer event-free and overall survival with a combination of inotuzumab ozogamicin (Besponsa) and bosutinib (Bosulif) than with standard chemotherapy combined with a targeted agent, investigators in a phase 1/2 study reported.
Among patients with relapsed or refractory Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) or chronic myeloid leukemia (Ph+ CML) in lymphoid blast phase treated with inotuzumab ozogamicin (Besponsa) and bosutinib (Bosulif), the median overall survival was 15.4 months. In contrast, median overall survival for similar patients treated with chemotherapy and a tyrosine kinase inhibitor (TKI) was less than 6 months, reported Nitin Jain, MD, and colleagues from the University of Texas MD Anderson Cancer Center in Houston.
The study was presented in a scientific poster session as part of the virtual annual congress of the European Hematology Association.
“Patients with relapsed/refractory Philadelphia chromosome–positive ALL/CML in lymphoid blast crisis are also best managed with a TKI targeting the constitutively active ABL kinase with the TKI selected based on presence of ABL kinase mutations and prior TKI history,” commented Marlise R. Luskin, MD, a leukemia specialist at the Dana-Farber Cancer Institute in Boston.
“A critical question for this patient population is whether these two approaches [TKI and inotuzumab ozogamicin] can be administered safely in combination. I congratulate MD Anderson for completion of this Phase I trial which demonstrates that inotuzumab and bosutinib can be safely combined with identification of a maximum tolerated dose of bosutinib 400 mg daily when administered in combination. I look forward to further studies that explore the efficacy of combination versus the approved single-agent regimen,” she said in an interview.
Study details
To see whether they could improve the dismal outcomes for patients with Ph+ ALL or Ph+ CML in lymphoid blast phase, they studied the combination of inotuzumab ozogamicin, an anti-CD22 monoclonal antibody conjugated to the cytotoxic antibiotic calicheamicin, and bosutinib, an inhibitor of the ABL kinase. Inotuzumab is approved in the United States for treatment of adults with relapsed or refractory B-cell precursor ALL, bosutinib is approved for the treatment of patients with newly-diagnosed chronic phase Ph+ CML and for adults with chronic, accelerated, or blast phase Ph+ CML with resistance or intolerance to prior therapy.
The investigators enrolled 16 patients with Ph+ ALL and 2 with Ph+ CML with bone marrow blasts greater than 5%, CD22 expressed on at least 20% of blasts, and good to fair performance status. The patients also had adequate organ function as measured by liver enzyme, total bilirubin, and serum creatinine levels. Patients with the T315I mutation, prior anti-CD22 therapy, active graft-versus-host disease, or liver disease were excluded.
The patients received inotuzumab 0.8 mg/m2 intravenously on day 1, they received 0.5 mg/m2 on days 8 and 15 of cycle 1, and they received 0.5 mg/m2 on days 1, 8, and 15 of cycles 2 through 6. Each cycle was 4 weeks. Patients who had a complete remission (CR), had complete cytogenetic remission (CCyR), or became negative for minimal residual disease (MRD) continued on 1 mg/m2 every 4 weeks. Bosutinib was dosed continuously day starting on the first day of cycle 1 and continued until disease progression or toxicity.
After a median follow-up of 36.7 months, 11 of the 18 patients had CRs, and 4 had CRs with incomplete recovery of hematologic counts. In addition, 13 of 16 patients with without diploid cytogenetics at the start of the study had CCyr; 14 patients had major molecular remission; 10 had complete molecular remission, and 11 were negative by flow cytometry.
As noted before, the median overall survival was 15.4 months. Event-free survival – time to lack of response, relapse, MRD relapse requiring therapy, or death – was 8 months. The event-free survival data were not censored for allogeneic stem cell transplant. Six patients underwent transplant while in remission.
The primary objective of the phase 1 trial was to evaluate safety of the combination and determine the maximum tolerated dose of bosutinib, which was determined to be 400 mg daily. At this dose level, one patient had a dose-limiting toxicity in the form of a grade 3 skin rash.
The most frequent adverse events were diarrhea and rash, in 50% of patients each, and nausea in 39% of patients. Grade 3 adverse events included were rash in three patients and reversible alanine aminotransferase and hyponatremia in one patient each. No patients developed veno-occlusive disease, and there no deaths within 30 days of the start of therapy.
Dr. Jain disclosed consultancy, honoraria, advisory board/committee activity, and research funding from Pfizer, maker of inotuzumab ozogamicin and bosutinib. Dr. Luskin reported no relevant disclosures.
SOURCE: Jain N et al. EHA25, Abstract EP396.
Patients with Philadelphia chromosome–positive acute lymphoblastic or chronic myeloid leukemias in lymphoid blast phase may have longer event-free and overall survival with a combination of inotuzumab ozogamicin (Besponsa) and bosutinib (Bosulif) than with standard chemotherapy combined with a targeted agent, investigators in a phase 1/2 study reported.
Among patients with relapsed or refractory Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) or chronic myeloid leukemia (Ph+ CML) in lymphoid blast phase treated with inotuzumab ozogamicin (Besponsa) and bosutinib (Bosulif), the median overall survival was 15.4 months. In contrast, median overall survival for similar patients treated with chemotherapy and a tyrosine kinase inhibitor (TKI) was less than 6 months, reported Nitin Jain, MD, and colleagues from the University of Texas MD Anderson Cancer Center in Houston.
The study was presented in a scientific poster session as part of the virtual annual congress of the European Hematology Association.
“Patients with relapsed/refractory Philadelphia chromosome–positive ALL/CML in lymphoid blast crisis are also best managed with a TKI targeting the constitutively active ABL kinase with the TKI selected based on presence of ABL kinase mutations and prior TKI history,” commented Marlise R. Luskin, MD, a leukemia specialist at the Dana-Farber Cancer Institute in Boston.
“A critical question for this patient population is whether these two approaches [TKI and inotuzumab ozogamicin] can be administered safely in combination. I congratulate MD Anderson for completion of this Phase I trial which demonstrates that inotuzumab and bosutinib can be safely combined with identification of a maximum tolerated dose of bosutinib 400 mg daily when administered in combination. I look forward to further studies that explore the efficacy of combination versus the approved single-agent regimen,” she said in an interview.
Study details
To see whether they could improve the dismal outcomes for patients with Ph+ ALL or Ph+ CML in lymphoid blast phase, they studied the combination of inotuzumab ozogamicin, an anti-CD22 monoclonal antibody conjugated to the cytotoxic antibiotic calicheamicin, and bosutinib, an inhibitor of the ABL kinase. Inotuzumab is approved in the United States for treatment of adults with relapsed or refractory B-cell precursor ALL, bosutinib is approved for the treatment of patients with newly-diagnosed chronic phase Ph+ CML and for adults with chronic, accelerated, or blast phase Ph+ CML with resistance or intolerance to prior therapy.
The investigators enrolled 16 patients with Ph+ ALL and 2 with Ph+ CML with bone marrow blasts greater than 5%, CD22 expressed on at least 20% of blasts, and good to fair performance status. The patients also had adequate organ function as measured by liver enzyme, total bilirubin, and serum creatinine levels. Patients with the T315I mutation, prior anti-CD22 therapy, active graft-versus-host disease, or liver disease were excluded.
The patients received inotuzumab 0.8 mg/m2 intravenously on day 1, they received 0.5 mg/m2 on days 8 and 15 of cycle 1, and they received 0.5 mg/m2 on days 1, 8, and 15 of cycles 2 through 6. Each cycle was 4 weeks. Patients who had a complete remission (CR), had complete cytogenetic remission (CCyR), or became negative for minimal residual disease (MRD) continued on 1 mg/m2 every 4 weeks. Bosutinib was dosed continuously day starting on the first day of cycle 1 and continued until disease progression or toxicity.
After a median follow-up of 36.7 months, 11 of the 18 patients had CRs, and 4 had CRs with incomplete recovery of hematologic counts. In addition, 13 of 16 patients with without diploid cytogenetics at the start of the study had CCyr; 14 patients had major molecular remission; 10 had complete molecular remission, and 11 were negative by flow cytometry.
As noted before, the median overall survival was 15.4 months. Event-free survival – time to lack of response, relapse, MRD relapse requiring therapy, or death – was 8 months. The event-free survival data were not censored for allogeneic stem cell transplant. Six patients underwent transplant while in remission.
The primary objective of the phase 1 trial was to evaluate safety of the combination and determine the maximum tolerated dose of bosutinib, which was determined to be 400 mg daily. At this dose level, one patient had a dose-limiting toxicity in the form of a grade 3 skin rash.
The most frequent adverse events were diarrhea and rash, in 50% of patients each, and nausea in 39% of patients. Grade 3 adverse events included were rash in three patients and reversible alanine aminotransferase and hyponatremia in one patient each. No patients developed veno-occlusive disease, and there no deaths within 30 days of the start of therapy.
Dr. Jain disclosed consultancy, honoraria, advisory board/committee activity, and research funding from Pfizer, maker of inotuzumab ozogamicin and bosutinib. Dr. Luskin reported no relevant disclosures.
SOURCE: Jain N et al. EHA25, Abstract EP396.
FROM EHA CONGRESS
HSCT may be best option for therapy-related ALL
Therapy-related acute lymphoblastic leukemia (tALL) is less common and less well known than therapy-related acute myeloid leukemia, but tALL also appears to be associated with poor-prognosis features, compared with de novo ALL, investigators said.
“Currently, this condition is not fully recognized by the [World Health Organization] classification, but it has emerged as a relevant and increasingly common form of ALL. There is no standardized therapy for tALL at this time due to the rarity of the condition. Therefore, more information regarding characteristics, prognosis, and treatment is needed,” wrote Brayan Merchán, MD, and colleagues at Princess Margaret Hospital in Toronto.
At their center, the median overall survival (OS) among 58 patients with tALL who received front line induction therapy was 13 months, although patients who were able to undergo hematopoietic stem cell transplant had a 400% longer OS than patients who did not receive HSCT, they reported in an electronic poster presented as part of the virtual annual congress of the European Hematology Association.
A hematologist-oncologist who has studied tALL agreed that it appears to be a distinct clinical entity from de novo ALL.
“It is distinct from the other ALL because the age [at diagnosis] is different, the cytogenetic and molecular profiles are different, and while responses are the same, it seems that survival is lower in cases who don’t go through bone marrow transplant as consolidation,” said Ibrahim Aldoss, MD, from City of Hope Medical Center in Duarte, Calif.
Dr. Aldoss, who was not involved in the study, was the lead author of a study published in 2018 which found that, “[a]lthough survival of therapy-related acute lymphoblastic leukemia was inferior to de novo cases, allogeneic hematopoietic cell transplantation outcomes were comparable for the two entities” (Haematologica. 2018 Oct; 103[10]:1662-8).
He noted that induction regimen options for patients with tALL may be limited because some patients may had previous exposures to cytotoxic chemotherapy agents – such as anthracyclines used in standard regimens for breast cancer – that have cumulative toxicities and lifetime dose limits.
In addition, “these patients tend to be older, because they went through another cancer and then developed therapy-related ALL, and usually they’re not eligible for pediatric-inspired regimens that we use more frequently in younger patients,” he said.
Retrospective study
Dr. Merchán and colleagues conducted a retrospective study of all consecutive adults with ALL treated at their center from 1999 to 2019 and followed until January 2020. Of this group, they identified 59 patients who had been exposed to chemotherapy or radiation for other diseases prior to their ALL diagnosis.
The mean age of the 59 patients (31 women and 28 men) was 54.7 years. In all, 34 had solid cancers and 25 had hematologic malignancies before their ALL diagnosis. The most common diagnosis was breast cancer in 15 patients, followed by multiple myeloma in 11, lymphoma in 7, and AML in 5. Other prior diagnoses were not specified.
Prior therapies included chemotherapy alone in 18 patients, radiotherapy alone in 19, and 20 had both treatment modalities (information about 2 remaining patients was not presented).
For the overall population the median time to tALL diagnosis was 5 years, but for 9 patients with the poor-prognosis MLL gene rearrangement the median time to tALL was just 21 months. The disease latency period was 21 months for patients who received chemotherapy, compared with 117 months for patients treated with radiotherapy.
The majority of patients (53) had B-phenotype ALL. Of the 49 for whom cytogenetic data were available, 41 had cytogenetic abnormalities, including the MLL rearrangement in 9, and complex karyotype in 7. Of all 59 patients, 12 had translocation t(9;22).
One patient did not undergo induction therapy for ALL because of poor performance status. All of the other patients received induction therapy, either a Dana-Farber Cancer Institute protocol in 44 patients, hyper-CVAD (cyclophosphamide, vincristine, doxorubicin, and dexamethasone) in 5, or blinatumomab in 3.
A complete response was seen in 41 patients (70%); 7 patients died during induction from causes attributed to therapy.
The mean follow-up for all patients was 27 months, and median overall survival was 13 months.
Median overall survival was 98 months for patients who underwent allogeneic HSCT versus a median of 19 months for patients who did not undergo transplant. This difference was not statistically significant, however, likely because of the small sample size.
Causes of death in 11 patients after transplant included relapse in 4 and graft-versus-host disease in 2 (other causes were not specified). Among the 34 patients who did not undergo HSCT following induction, 15 died from disease progression.
“From our results, tALL patients who were able to receive HSCT had better OS. Our data also supports the notion that tALL may be distinct entity with poor prognosis features compared to de novo ALL,” the investigators concluded.
The authors did not disclose a funding source. Dr. Merchán and Dr. Aldoss reported no relevant disclosures.
SOURCE: Merchán B et al. EHA25, Abstract EP391.
Therapy-related acute lymphoblastic leukemia (tALL) is less common and less well known than therapy-related acute myeloid leukemia, but tALL also appears to be associated with poor-prognosis features, compared with de novo ALL, investigators said.
“Currently, this condition is not fully recognized by the [World Health Organization] classification, but it has emerged as a relevant and increasingly common form of ALL. There is no standardized therapy for tALL at this time due to the rarity of the condition. Therefore, more information regarding characteristics, prognosis, and treatment is needed,” wrote Brayan Merchán, MD, and colleagues at Princess Margaret Hospital in Toronto.
At their center, the median overall survival (OS) among 58 patients with tALL who received front line induction therapy was 13 months, although patients who were able to undergo hematopoietic stem cell transplant had a 400% longer OS than patients who did not receive HSCT, they reported in an electronic poster presented as part of the virtual annual congress of the European Hematology Association.
A hematologist-oncologist who has studied tALL agreed that it appears to be a distinct clinical entity from de novo ALL.
“It is distinct from the other ALL because the age [at diagnosis] is different, the cytogenetic and molecular profiles are different, and while responses are the same, it seems that survival is lower in cases who don’t go through bone marrow transplant as consolidation,” said Ibrahim Aldoss, MD, from City of Hope Medical Center in Duarte, Calif.
Dr. Aldoss, who was not involved in the study, was the lead author of a study published in 2018 which found that, “[a]lthough survival of therapy-related acute lymphoblastic leukemia was inferior to de novo cases, allogeneic hematopoietic cell transplantation outcomes were comparable for the two entities” (Haematologica. 2018 Oct; 103[10]:1662-8).
He noted that induction regimen options for patients with tALL may be limited because some patients may had previous exposures to cytotoxic chemotherapy agents – such as anthracyclines used in standard regimens for breast cancer – that have cumulative toxicities and lifetime dose limits.
In addition, “these patients tend to be older, because they went through another cancer and then developed therapy-related ALL, and usually they’re not eligible for pediatric-inspired regimens that we use more frequently in younger patients,” he said.
Retrospective study
Dr. Merchán and colleagues conducted a retrospective study of all consecutive adults with ALL treated at their center from 1999 to 2019 and followed until January 2020. Of this group, they identified 59 patients who had been exposed to chemotherapy or radiation for other diseases prior to their ALL diagnosis.
The mean age of the 59 patients (31 women and 28 men) was 54.7 years. In all, 34 had solid cancers and 25 had hematologic malignancies before their ALL diagnosis. The most common diagnosis was breast cancer in 15 patients, followed by multiple myeloma in 11, lymphoma in 7, and AML in 5. Other prior diagnoses were not specified.
Prior therapies included chemotherapy alone in 18 patients, radiotherapy alone in 19, and 20 had both treatment modalities (information about 2 remaining patients was not presented).
For the overall population the median time to tALL diagnosis was 5 years, but for 9 patients with the poor-prognosis MLL gene rearrangement the median time to tALL was just 21 months. The disease latency period was 21 months for patients who received chemotherapy, compared with 117 months for patients treated with radiotherapy.
The majority of patients (53) had B-phenotype ALL. Of the 49 for whom cytogenetic data were available, 41 had cytogenetic abnormalities, including the MLL rearrangement in 9, and complex karyotype in 7. Of all 59 patients, 12 had translocation t(9;22).
One patient did not undergo induction therapy for ALL because of poor performance status. All of the other patients received induction therapy, either a Dana-Farber Cancer Institute protocol in 44 patients, hyper-CVAD (cyclophosphamide, vincristine, doxorubicin, and dexamethasone) in 5, or blinatumomab in 3.
A complete response was seen in 41 patients (70%); 7 patients died during induction from causes attributed to therapy.
The mean follow-up for all patients was 27 months, and median overall survival was 13 months.
Median overall survival was 98 months for patients who underwent allogeneic HSCT versus a median of 19 months for patients who did not undergo transplant. This difference was not statistically significant, however, likely because of the small sample size.
Causes of death in 11 patients after transplant included relapse in 4 and graft-versus-host disease in 2 (other causes were not specified). Among the 34 patients who did not undergo HSCT following induction, 15 died from disease progression.
“From our results, tALL patients who were able to receive HSCT had better OS. Our data also supports the notion that tALL may be distinct entity with poor prognosis features compared to de novo ALL,” the investigators concluded.
The authors did not disclose a funding source. Dr. Merchán and Dr. Aldoss reported no relevant disclosures.
SOURCE: Merchán B et al. EHA25, Abstract EP391.
Therapy-related acute lymphoblastic leukemia (tALL) is less common and less well known than therapy-related acute myeloid leukemia, but tALL also appears to be associated with poor-prognosis features, compared with de novo ALL, investigators said.
“Currently, this condition is not fully recognized by the [World Health Organization] classification, but it has emerged as a relevant and increasingly common form of ALL. There is no standardized therapy for tALL at this time due to the rarity of the condition. Therefore, more information regarding characteristics, prognosis, and treatment is needed,” wrote Brayan Merchán, MD, and colleagues at Princess Margaret Hospital in Toronto.
At their center, the median overall survival (OS) among 58 patients with tALL who received front line induction therapy was 13 months, although patients who were able to undergo hematopoietic stem cell transplant had a 400% longer OS than patients who did not receive HSCT, they reported in an electronic poster presented as part of the virtual annual congress of the European Hematology Association.
A hematologist-oncologist who has studied tALL agreed that it appears to be a distinct clinical entity from de novo ALL.
“It is distinct from the other ALL because the age [at diagnosis] is different, the cytogenetic and molecular profiles are different, and while responses are the same, it seems that survival is lower in cases who don’t go through bone marrow transplant as consolidation,” said Ibrahim Aldoss, MD, from City of Hope Medical Center in Duarte, Calif.
Dr. Aldoss, who was not involved in the study, was the lead author of a study published in 2018 which found that, “[a]lthough survival of therapy-related acute lymphoblastic leukemia was inferior to de novo cases, allogeneic hematopoietic cell transplantation outcomes were comparable for the two entities” (Haematologica. 2018 Oct; 103[10]:1662-8).
He noted that induction regimen options for patients with tALL may be limited because some patients may had previous exposures to cytotoxic chemotherapy agents – such as anthracyclines used in standard regimens for breast cancer – that have cumulative toxicities and lifetime dose limits.
In addition, “these patients tend to be older, because they went through another cancer and then developed therapy-related ALL, and usually they’re not eligible for pediatric-inspired regimens that we use more frequently in younger patients,” he said.
Retrospective study
Dr. Merchán and colleagues conducted a retrospective study of all consecutive adults with ALL treated at their center from 1999 to 2019 and followed until January 2020. Of this group, they identified 59 patients who had been exposed to chemotherapy or radiation for other diseases prior to their ALL diagnosis.
The mean age of the 59 patients (31 women and 28 men) was 54.7 years. In all, 34 had solid cancers and 25 had hematologic malignancies before their ALL diagnosis. The most common diagnosis was breast cancer in 15 patients, followed by multiple myeloma in 11, lymphoma in 7, and AML in 5. Other prior diagnoses were not specified.
Prior therapies included chemotherapy alone in 18 patients, radiotherapy alone in 19, and 20 had both treatment modalities (information about 2 remaining patients was not presented).
For the overall population the median time to tALL diagnosis was 5 years, but for 9 patients with the poor-prognosis MLL gene rearrangement the median time to tALL was just 21 months. The disease latency period was 21 months for patients who received chemotherapy, compared with 117 months for patients treated with radiotherapy.
The majority of patients (53) had B-phenotype ALL. Of the 49 for whom cytogenetic data were available, 41 had cytogenetic abnormalities, including the MLL rearrangement in 9, and complex karyotype in 7. Of all 59 patients, 12 had translocation t(9;22).
One patient did not undergo induction therapy for ALL because of poor performance status. All of the other patients received induction therapy, either a Dana-Farber Cancer Institute protocol in 44 patients, hyper-CVAD (cyclophosphamide, vincristine, doxorubicin, and dexamethasone) in 5, or blinatumomab in 3.
A complete response was seen in 41 patients (70%); 7 patients died during induction from causes attributed to therapy.
The mean follow-up for all patients was 27 months, and median overall survival was 13 months.
Median overall survival was 98 months for patients who underwent allogeneic HSCT versus a median of 19 months for patients who did not undergo transplant. This difference was not statistically significant, however, likely because of the small sample size.
Causes of death in 11 patients after transplant included relapse in 4 and graft-versus-host disease in 2 (other causes were not specified). Among the 34 patients who did not undergo HSCT following induction, 15 died from disease progression.
“From our results, tALL patients who were able to receive HSCT had better OS. Our data also supports the notion that tALL may be distinct entity with poor prognosis features compared to de novo ALL,” the investigators concluded.
The authors did not disclose a funding source. Dr. Merchán and Dr. Aldoss reported no relevant disclosures.
SOURCE: Merchán B et al. EHA25, Abstract EP391.
FROM EHA CONGRESS
Omitting whole body irradiation before HSCT: Trial stopped early
Hematopoietic stem cell transplantation (HSCT) may offer the chance of a cure for patients with leukemia and other blood cancers, but the process of preparing the body to receive such a transplant can be brutal, involving whole body irradiation as well as chemotherapy conditioning. New results show that both steps are needed: a trial that omitted whole body irradiation in young patients with acute lymphoblastic leukemia (ALL) was stopped early because of significantly poorer outcomes.
The multicenter, global FORUM (For Omitting Radiation Under Majority Age) trial involved 75 centers in 17 countries between 2013 and 2018.
“Our study shows significantly better outcomes for total body irradiation compared to myeloablative chemo-conditioning arms, with no differences between the [two] chemo-conditioning groups,” concluded Christina Peters, MD, professor of pediatrics in the department of stem cell transplantation at St Anna Children’s Hospital in Vienna.
, she added.
Dr. Peters presented the findings as part of the virtual annual congress of the European Hematology Association.
Describing the results as “sobering,” session comoderator Shai Izraeli, MD, director of the department of hematology-oncology at Schneider Children’s Medical Center, in Petah Tikva, Israel, said an online comment from the virtual meeting audience reflected the reaction to these unwelcome results: “So we are still stuck with total body irradiation?”
Dr. Peters said the good news is that the number of patients needing to undergo stem cell transplants is low, and with research advances, may hopefully drop even further.
“Only 10% of patients under the age of 18 nowadays undergo allogeneic HSCT, and perhaps in the future that will become even less if we are able to rescue some of the groups with other immunological measures such as CAR-T cells and antibodies,” she said.
“I think it is very important to better identify those who really need total body irradiation in the future,” she added.
In an interview, Dr. Izraeli agreed.
“The prognosis of children after bone marrow transplantation is excellent – the majority are cured from their leukemia,” he said. “And we have to remember that those who undergo bone marrow transplant have the worst leukemias.”
He pointed out that, in fact, contemporary chemotherapy alone is effective in the treatment of more than 90% of patients with ALL younger than aged 18.
For the 10% of patients who do not respond to chemotherapy alone and undergo allogeneic HSCT, about 50%-80% of pediatric patients who have resistant leukemia are cured. However, the total body irradiation used to prepare the body to receive the transplant is linked to potentially serious consequences later in life, including sterility, lung problems, growth retardation, and secondary cancer.
To determine if the irradiation component could be safely replaced with a chemotherapy-based conditioning approach, Dr. Peters and colleagues conducted the FORUM trial.
In total 413 patients undergoing HSCT were enrolled and randomized to pretransplant conditioning with total body irradiation and etoposide (n = 202) or a chemotherapy-only approach with fludarabine/thiotepa/busulfan (flu/thio/bu; n = 99) or fludarabine/thiotepa/treosulfan (treo; n = 93).
Most patients (72%) had B-cell precursor ALL and 23% had T-cell ALL. Just over half (54%) were transplanted in first complete remission (CR1), 40% in CR2, and 4% in CR3.
The source of stem cells was bone marrow for most patients (82%); peripheral blood stem cell for 12%, and cord blood for 4%.
Study stopped early
The aim of the study was to demonstrate noninferiority with the chemotherapy approach.
However, the significantly inferior outcome observed in the chemotherapy-only group led to randomization being halted in March 2019.
The 2-year overall survival in the intent-to-treat (ITT) analysis, with a mean observation time of 2.1 years, was 0.75 ± 0.04 for chemo-conditioning versus 0.91 ± 0.02 for total body irradiation/etoposide (ITT P < .001).
The ITT analysis showed relapses were significantly higher in the chemo-conditioning group (2-year cumulative incidence of relapse [CIR], 0.33) compared with the total body irradiation group (CIR, 0.12; P < .001).
The 2-year event-free survival (EFS) rate was also significantly higher in the total body irradiation group (0.86 vs 0.58; P < .001), and transplant-related mortality over 2 years was lower with total body irradiation (0.02 vs 0.09; P = .02).
A per-protocol analysis showed the 2-year overall survival to be the same in the two chemotherapy groups (both 0.77 ± 0.05) compared with 0.91 ± 0.02 in the total body irradiation group (P = .003).
“In this cohort [the 91% overall survival rate] may even be lower than contemporary intensive frontline therapy results that are achieved nowadays,” Dr. Peters said.
In looking at subgroups, there were no significant differences according to age group or cancer phenotype, while MLL rearrangement was associated with higher relapse incidence.
Remission status was found to notably influence EFS, dropping from 0.91 in CR1 patients with total body irradiation to 0.76 in CR2 patients. However, total body irradiation remained significantly higher compared with the chemo-conditioning groups in CR1 (P = .004) and CR2 (P < .001).
Transplant-related mortality was not significantly different between the total body irradiation and chemo-conditioning groups in the CR1 or CR2 groups (P = .09 and P = .18, respectively), despite the significant difference when remission status was not included.
Overall, “we tried to identify subgroups in which total body irradiation might be eliminated, however in all analyses, total body irradiation was better than chemo-conditioning in all arms,” Dr. Peters said.
Meanwhile, the findings underscore that even when patients cannot receive total body irradiation, the alternative chemo-conditioning therapy in fact shows favorable efficacy on its own, Dr. Izraeli said.
“The prognosis of the chemotherapy group is also quite remarkably good, although less than the total body irradiation arm. This means that if for some reason total body irradiation cannot be given, the chemotherapy is a very reasonable alternative.”
Dr. Peters has reported relationships with Amgen, Novartis, Pfizer, Medac, Jazz, and Neovii. Dr. Izraeli has reported no relevant financial relationships.
SOURCE: EHA Congress. Abstract S102.
A version of this article originally appeared on Medscape.com.
Hematopoietic stem cell transplantation (HSCT) may offer the chance of a cure for patients with leukemia and other blood cancers, but the process of preparing the body to receive such a transplant can be brutal, involving whole body irradiation as well as chemotherapy conditioning. New results show that both steps are needed: a trial that omitted whole body irradiation in young patients with acute lymphoblastic leukemia (ALL) was stopped early because of significantly poorer outcomes.
The multicenter, global FORUM (For Omitting Radiation Under Majority Age) trial involved 75 centers in 17 countries between 2013 and 2018.
“Our study shows significantly better outcomes for total body irradiation compared to myeloablative chemo-conditioning arms, with no differences between the [two] chemo-conditioning groups,” concluded Christina Peters, MD, professor of pediatrics in the department of stem cell transplantation at St Anna Children’s Hospital in Vienna.
, she added.
Dr. Peters presented the findings as part of the virtual annual congress of the European Hematology Association.
Describing the results as “sobering,” session comoderator Shai Izraeli, MD, director of the department of hematology-oncology at Schneider Children’s Medical Center, in Petah Tikva, Israel, said an online comment from the virtual meeting audience reflected the reaction to these unwelcome results: “So we are still stuck with total body irradiation?”
Dr. Peters said the good news is that the number of patients needing to undergo stem cell transplants is low, and with research advances, may hopefully drop even further.
“Only 10% of patients under the age of 18 nowadays undergo allogeneic HSCT, and perhaps in the future that will become even less if we are able to rescue some of the groups with other immunological measures such as CAR-T cells and antibodies,” she said.
“I think it is very important to better identify those who really need total body irradiation in the future,” she added.
In an interview, Dr. Izraeli agreed.
“The prognosis of children after bone marrow transplantation is excellent – the majority are cured from their leukemia,” he said. “And we have to remember that those who undergo bone marrow transplant have the worst leukemias.”
He pointed out that, in fact, contemporary chemotherapy alone is effective in the treatment of more than 90% of patients with ALL younger than aged 18.
For the 10% of patients who do not respond to chemotherapy alone and undergo allogeneic HSCT, about 50%-80% of pediatric patients who have resistant leukemia are cured. However, the total body irradiation used to prepare the body to receive the transplant is linked to potentially serious consequences later in life, including sterility, lung problems, growth retardation, and secondary cancer.
To determine if the irradiation component could be safely replaced with a chemotherapy-based conditioning approach, Dr. Peters and colleagues conducted the FORUM trial.
In total 413 patients undergoing HSCT were enrolled and randomized to pretransplant conditioning with total body irradiation and etoposide (n = 202) or a chemotherapy-only approach with fludarabine/thiotepa/busulfan (flu/thio/bu; n = 99) or fludarabine/thiotepa/treosulfan (treo; n = 93).
Most patients (72%) had B-cell precursor ALL and 23% had T-cell ALL. Just over half (54%) were transplanted in first complete remission (CR1), 40% in CR2, and 4% in CR3.
The source of stem cells was bone marrow for most patients (82%); peripheral blood stem cell for 12%, and cord blood for 4%.
Study stopped early
The aim of the study was to demonstrate noninferiority with the chemotherapy approach.
However, the significantly inferior outcome observed in the chemotherapy-only group led to randomization being halted in March 2019.
The 2-year overall survival in the intent-to-treat (ITT) analysis, with a mean observation time of 2.1 years, was 0.75 ± 0.04 for chemo-conditioning versus 0.91 ± 0.02 for total body irradiation/etoposide (ITT P < .001).
The ITT analysis showed relapses were significantly higher in the chemo-conditioning group (2-year cumulative incidence of relapse [CIR], 0.33) compared with the total body irradiation group (CIR, 0.12; P < .001).
The 2-year event-free survival (EFS) rate was also significantly higher in the total body irradiation group (0.86 vs 0.58; P < .001), and transplant-related mortality over 2 years was lower with total body irradiation (0.02 vs 0.09; P = .02).
A per-protocol analysis showed the 2-year overall survival to be the same in the two chemotherapy groups (both 0.77 ± 0.05) compared with 0.91 ± 0.02 in the total body irradiation group (P = .003).
“In this cohort [the 91% overall survival rate] may even be lower than contemporary intensive frontline therapy results that are achieved nowadays,” Dr. Peters said.
In looking at subgroups, there were no significant differences according to age group or cancer phenotype, while MLL rearrangement was associated with higher relapse incidence.
Remission status was found to notably influence EFS, dropping from 0.91 in CR1 patients with total body irradiation to 0.76 in CR2 patients. However, total body irradiation remained significantly higher compared with the chemo-conditioning groups in CR1 (P = .004) and CR2 (P < .001).
Transplant-related mortality was not significantly different between the total body irradiation and chemo-conditioning groups in the CR1 or CR2 groups (P = .09 and P = .18, respectively), despite the significant difference when remission status was not included.
Overall, “we tried to identify subgroups in which total body irradiation might be eliminated, however in all analyses, total body irradiation was better than chemo-conditioning in all arms,” Dr. Peters said.
Meanwhile, the findings underscore that even when patients cannot receive total body irradiation, the alternative chemo-conditioning therapy in fact shows favorable efficacy on its own, Dr. Izraeli said.
“The prognosis of the chemotherapy group is also quite remarkably good, although less than the total body irradiation arm. This means that if for some reason total body irradiation cannot be given, the chemotherapy is a very reasonable alternative.”
Dr. Peters has reported relationships with Amgen, Novartis, Pfizer, Medac, Jazz, and Neovii. Dr. Izraeli has reported no relevant financial relationships.
SOURCE: EHA Congress. Abstract S102.
A version of this article originally appeared on Medscape.com.
Hematopoietic stem cell transplantation (HSCT) may offer the chance of a cure for patients with leukemia and other blood cancers, but the process of preparing the body to receive such a transplant can be brutal, involving whole body irradiation as well as chemotherapy conditioning. New results show that both steps are needed: a trial that omitted whole body irradiation in young patients with acute lymphoblastic leukemia (ALL) was stopped early because of significantly poorer outcomes.
The multicenter, global FORUM (For Omitting Radiation Under Majority Age) trial involved 75 centers in 17 countries between 2013 and 2018.
“Our study shows significantly better outcomes for total body irradiation compared to myeloablative chemo-conditioning arms, with no differences between the [two] chemo-conditioning groups,” concluded Christina Peters, MD, professor of pediatrics in the department of stem cell transplantation at St Anna Children’s Hospital in Vienna.
, she added.
Dr. Peters presented the findings as part of the virtual annual congress of the European Hematology Association.
Describing the results as “sobering,” session comoderator Shai Izraeli, MD, director of the department of hematology-oncology at Schneider Children’s Medical Center, in Petah Tikva, Israel, said an online comment from the virtual meeting audience reflected the reaction to these unwelcome results: “So we are still stuck with total body irradiation?”
Dr. Peters said the good news is that the number of patients needing to undergo stem cell transplants is low, and with research advances, may hopefully drop even further.
“Only 10% of patients under the age of 18 nowadays undergo allogeneic HSCT, and perhaps in the future that will become even less if we are able to rescue some of the groups with other immunological measures such as CAR-T cells and antibodies,” she said.
“I think it is very important to better identify those who really need total body irradiation in the future,” she added.
In an interview, Dr. Izraeli agreed.
“The prognosis of children after bone marrow transplantation is excellent – the majority are cured from their leukemia,” he said. “And we have to remember that those who undergo bone marrow transplant have the worst leukemias.”
He pointed out that, in fact, contemporary chemotherapy alone is effective in the treatment of more than 90% of patients with ALL younger than aged 18.
For the 10% of patients who do not respond to chemotherapy alone and undergo allogeneic HSCT, about 50%-80% of pediatric patients who have resistant leukemia are cured. However, the total body irradiation used to prepare the body to receive the transplant is linked to potentially serious consequences later in life, including sterility, lung problems, growth retardation, and secondary cancer.
To determine if the irradiation component could be safely replaced with a chemotherapy-based conditioning approach, Dr. Peters and colleagues conducted the FORUM trial.
In total 413 patients undergoing HSCT were enrolled and randomized to pretransplant conditioning with total body irradiation and etoposide (n = 202) or a chemotherapy-only approach with fludarabine/thiotepa/busulfan (flu/thio/bu; n = 99) or fludarabine/thiotepa/treosulfan (treo; n = 93).
Most patients (72%) had B-cell precursor ALL and 23% had T-cell ALL. Just over half (54%) were transplanted in first complete remission (CR1), 40% in CR2, and 4% in CR3.
The source of stem cells was bone marrow for most patients (82%); peripheral blood stem cell for 12%, and cord blood for 4%.
Study stopped early
The aim of the study was to demonstrate noninferiority with the chemotherapy approach.
However, the significantly inferior outcome observed in the chemotherapy-only group led to randomization being halted in March 2019.
The 2-year overall survival in the intent-to-treat (ITT) analysis, with a mean observation time of 2.1 years, was 0.75 ± 0.04 for chemo-conditioning versus 0.91 ± 0.02 for total body irradiation/etoposide (ITT P < .001).
The ITT analysis showed relapses were significantly higher in the chemo-conditioning group (2-year cumulative incidence of relapse [CIR], 0.33) compared with the total body irradiation group (CIR, 0.12; P < .001).
The 2-year event-free survival (EFS) rate was also significantly higher in the total body irradiation group (0.86 vs 0.58; P < .001), and transplant-related mortality over 2 years was lower with total body irradiation (0.02 vs 0.09; P = .02).
A per-protocol analysis showed the 2-year overall survival to be the same in the two chemotherapy groups (both 0.77 ± 0.05) compared with 0.91 ± 0.02 in the total body irradiation group (P = .003).
“In this cohort [the 91% overall survival rate] may even be lower than contemporary intensive frontline therapy results that are achieved nowadays,” Dr. Peters said.
In looking at subgroups, there were no significant differences according to age group or cancer phenotype, while MLL rearrangement was associated with higher relapse incidence.
Remission status was found to notably influence EFS, dropping from 0.91 in CR1 patients with total body irradiation to 0.76 in CR2 patients. However, total body irradiation remained significantly higher compared with the chemo-conditioning groups in CR1 (P = .004) and CR2 (P < .001).
Transplant-related mortality was not significantly different between the total body irradiation and chemo-conditioning groups in the CR1 or CR2 groups (P = .09 and P = .18, respectively), despite the significant difference when remission status was not included.
Overall, “we tried to identify subgroups in which total body irradiation might be eliminated, however in all analyses, total body irradiation was better than chemo-conditioning in all arms,” Dr. Peters said.
Meanwhile, the findings underscore that even when patients cannot receive total body irradiation, the alternative chemo-conditioning therapy in fact shows favorable efficacy on its own, Dr. Izraeli said.
“The prognosis of the chemotherapy group is also quite remarkably good, although less than the total body irradiation arm. This means that if for some reason total body irradiation cannot be given, the chemotherapy is a very reasonable alternative.”
Dr. Peters has reported relationships with Amgen, Novartis, Pfizer, Medac, Jazz, and Neovii. Dr. Izraeli has reported no relevant financial relationships.
SOURCE: EHA Congress. Abstract S102.
A version of this article originally appeared on Medscape.com.
FROM EHA CONGRESS