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Causes of Inferior Outcome in Adolescents and Young Adults with Acute Lymphoblastic Leukemia: Across Oncology Services and Regardless of Clinical Trial Enrollment.

ABSTRACT: Background: Adolescents and young adults (AYA: 15-39 years) with acute lymphoblastic leukemia (ALL) have inferior survival when compared with children (1-14 years). An approach is lacking that includes both patients enrolled and not enrolled in clinical trials, and includes the contribution of health care delivery, treatment, and clinical prognosticators.Methods: We assembled a retrospective cohort of ALL patients diagnosed between 1-39 years (AYA: n = 93; child: n = 91) and treated at a single institution between 1990 and 2010, irrespective of clinical trial enrollment. We modeled relapse risk (i) during therapy and (ii) after completing therapy.Results: On-therapy relapse: AYA experienced an increased risk of on-therapy relapse versus children (HR, 10.5; P = 0.004). In multivariable analysis restricted to AYA, independent predictors of relapse included lack of clinical trial enrollment (HR, 2.6, P = 0.04) and nonwhite race/ethnicity (HR, 2.2; P = 0.05). Relapse after completing therapy: When compared with children, AYA experienced an increased risk of relapse after completing therapy (HR, 7.7; P < 0.001). In multivariable analysis restricted to AYA, longer therapy (months of maintenance: HR, 0.7; P < 0.001; months of consolidation: HR, 0.8; P = 0.03) protected against relapse.Conclusions: Among AYA, aspects of health care delivery (clinical trial enrollment, nonwhite race/ethnicity) are associated with relapse during therapy, and aspects of treatment (shorter duration of maintenance and consolidation) are associated with relapse after completing therapy.Impact: These findings highlight the importance of clinical trial enrollment and therapy duration (maintenance, consolidation) in ensuring durable remissions in AYA ALL. Future studies encompassing health care delivery, treatment, and biology are needed. Cancer Epidemiol Biomarkers Prev; 27(10); 1133-41. ©2018 AACR.

SUBMITTER: Wolfson JA

PROVIDER: S-EPMC6238217 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature

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Causes of Inferior Outcome in Adolescents and Young Adults with Acute Lymphoblastic Leukemia: Across Oncology Services and Regardless of Clinical Trial Enrollment.

Wolfson Julie A JA Richman Joshua S JS Sun Can-Lan CL Landier Wendy W Leung Karen K Smith Eileen P EP O'Donnell Margaret M Bhatia Smita S

Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology 20180927 10

Background: Adolescents and young adults (AYA: 15-39 years) with acute lymphoblastic leukemia (ALL) have inferior survival when compared with children (1-14 years). An approach is lacking that includes both patients enrolled and not enrolled in clinical trials, and includes the contribution of health care delivery, treatment, and clinical prognosticators.Methods: We assembled a retrospective cohort of ALL patients diagnosed between 1-39 years (AYA: n = 93; child: n = ...[more]

PMID: 30262597

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Project description:Purpose Addition of imatinib to intensive chemotherapy improved survival for children and young adults with Philadelphia chromosome-positive acute lymphoblastic leukemia. Compared with imatinib, dasatinib has increased potency, CNS penetration, and activity against imatinib-resistant clones. Patients and Methods Children's Oncology Group (COG) trial AALL0622 (Bristol Myers Squibb trial CA180-204) tested safety and feasibility of adding dasatinib to intensive chemotherapy starting at induction day 15 in patients with newly diagnosed Philadelphia chromosome-positive acute lymphoblastic leukemia age 1 to 30 years. Allogeneic hematopoietic stem-cell transplantation (HSCT) was recommended for patients at high risk based on slow response and for those with a matched family donor regardless of response after at least 11 weeks of therapy. Patients at standard risk based on rapid response received chemotherapy plus dasatinib for an additional 120 weeks. Patients with overt CNS leukemia received cranial irradiation. Results Sixty eligible patients were enrolled. Five-year overall (OS) and event-free survival rates (± standard deviations [SD]) were 86% ± 5% and 60% ± 7% overall, 87% ± 5% and 61% ± 7% for standard-risk patients (n = 48; 19% underwent HSCT), and 89% ± 13% and 67% ± 19% for high-risk patients (n = 9; 89% underwent HSCT), respectively. Five-year cumulative incidence (± SD) of CNS relapse was 15% ± 6%. Outcomes (± SDs) were similar to those in COG AALL0031, which used the same chemotherapy with continuous imatinib: 5-year OS of 81% ± 6% versus 86% ± 5% ( P = .63) and 5-year disease-free survival of 68% ± 7% versus 60% ± 7% ( P = 0.31) for AALL0031 versus AALL0622, respectively. IKZF1 deletions, present in 56% of tested patients, were associated with significantly inferior OS and event-free survival overall and in standard-risk patients. Conclusion Dasatinib was well tolerated with chemotherapy and provided outcomes similar to those with imatinib in COG AALL0031, where all patients received cranial irradiation. Our results support limiting HSCT to slow responders and suggest a potential role for transplantation in rapid responders with IKZF1 deletions.

Project description:Background: Adolescents and young adults (AYA; 15-39 years) with acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML) experience inferior survival when compared with children. Impact of care at NCI-designated Comprehensive Cancer Centers (CCC) or Children's Oncology Group sites (COG) on survival disparities remains unstudied.Methods: Using the Los Angeles cancer registry, we identified 1,870 ALL or AML patients between 1 and 39 years at diagnosis. Cox regression analyses assessed risk of mortality; younger age + CCC/COG served as the referent group. Logistic regression was used to determine odds of care at CCC/COG, adjusting for variables above.Results: ALL outcome: AYAs at non-CCC/COG experienced inferior survival (15-21 years: HR = 1.9, P = 0.005; 22-29 years: HR = 2.6, P < 0.001; 30-39 years: HR = 3.0, P < 0.001). Outcome at CCC/COG was comparable between children and young AYAs (15-21 years: HR = 1.3, P = 0.3; 22-29 years: HR = 1.2, P = 0.2) but was inferior for 30- to 39-year-olds (HR = 3.4, P < 0.001). AML outcome: AYAs at non-CCC/COG experienced inferior outcome (15-21 years: HR = 1.8, P = 0.02; 22-39 years: HR = 1.4, P = 0.06). Outcome at CCC/COG was comparable between children and 15- to 21-year-olds (HR = 1.3, P = 0.4) but was inferior for 22- to 39-year-olds (HR = 1.7, P = 0.05). Access: 15- to 21-year-olds were less likely to use CCC/COG than children (P < 0.001). In 22- to 39-year-olds, public/uninsured (ALL: P = 0.004; AML<0.001), African American/Hispanics (ALL: P = 0.03), and 30- to 39-year-olds (ALL: P = 0.03) were less likely to use CCC/COG.Conclusions: Poor survival in AYAs with ALL and AML is mitigated by care at CCC/COG. Barriers to CCC/COG care include public/uninsured, and African American/Hispanic race/ethnicity.Impact: Care at CCC/COG explains, in part, inferior outcomes in AYAs with ALL and AML. Key sociodemographic factors serve as barriers to care at specialized centers. Cancer Epidemiol Biomarkers Prev; 26(3); 312-20. ©2017 AACR.

Dataset Information

Causes of Inferior Outcome in Adolescents and Young Adults with Acute Lymphoblastic Leukemia: Across Oncology Services and Regardless of Clinical Trial Enrollment.

Publications

Causes of Inferior Outcome in Adolescents and Young Adults with Acute Lymphoblastic Leukemia: Across Oncology Services and Regardless of Clinical Trial Enrollment.

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