1.
Superior survival with pediatric-style chemotherapy compared to myeloablative allogeneic hematopoietic cell transplantation in older adolescents and young adults with Ph-negative acute lymphoblastic leukemia in first complete remission: analysis from CALGB 10403 and the CIBMTR
Wieduwilt, M. J., Stock, W., Advani, A., Luger, S., Larson, R. A., Tallman, M., Appelbaum, F., Zhang, M. J., Bo-Subait, K., Wang, H. L., et al
Leukemia. 2021
Abstract
Optimal post-remission therapy for adolescents and young adults (AYAs) with Ph-negative acute lymphoblastic leukemia (ALL) in first complete remission (CR1) is not established. We compared overall survival (OS), disease-free survival (DFS), relapse, and non-relapse mortality (NRM) for patients receiving post-remission therapy on CALGB 10403 to a cohort undergoing myeloablative (MA) allogeneic hematopoietic cell transplantation (HCT) in CR1. In univariate analysis, OS was superior with chemotherapy compared to MA allogeneic HCT (3-year OS 77% vs. 53%, P?0.001). In multivariate analysis, allogeneic HCT showed inferior OS (HR 2.00, 95% CI 1.5-2.66, P?0.001), inferior DFS (HR 1.62, 95% CI 1.25-2.12, P?0.001), and increased NRM (HR 5.41, 95% CI 3.23-9.06, P?0.001) compared to chemotherapy. A higher 5-year relapse incidence was seen with chemotherapy compared to allogeneic HCT (34% vs. 23%, P?=?0.011). Obesity was independently associated with inferior OS (HR 2.17, 95% CI 1.63-2.89, P?0.001), inferior DFS (HR 1.97, 95% CI 1.51-2.57, P?0.001), increased relapse (1.84, 95% CI 1.31-2.59, P?0.001), and increased NRM (HR 2.10, 95% CI 1.37-3.23, P?0.001). For AYA ALL patients in CR1, post-remission therapy with pediatric-style chemotherapy is superior to MA allogeneic HCT for OS, DFS, and NRM.
2.
Pediatric-inspired therapy compared to allografting for Philadelphia chromosome-negative adult ALL in first complete remission
Seftel, M. D., Neuberg, D., Zhang, M. J., Wang, H. L., Ballen, K. K., Bergeron, J., Couban, S., Freytes, C. O., Hamadani, M., Kharfan-Dabaja, M. A., et al
American Journal of Hematology. 2016;91(3):322-9
Abstract
For adults with Philadelphia chromosome-negative (Ph-) acute lymphoblastic leukemia (ALL) in first complete remission (CR1), allogeneic hematopoietic cell transplantation (HCT) is an established curative strategy. However, pediatric-inspired chemotherapy may also offer durable leukemia-free survival in the absence of HCT. We compared 422 HCT recipients aged 18-50 years with Ph-ALL in CR1 reported to the CIBMTR with an age-matched concurrent cohort of 108 Ph- ALL CR1 patients who received a Dana-Farber Consortium pediatric-inspired non-HCT regimen. At 4 years of follow-up, incidence of relapse after HCT was 24% (95% CI 19-28) versus 23% (95% CI 15-32) for the non-HCT (chemo) cohort (P=0.97). Treatment-related mortality (TRM) was higher in the HCT cohort [HCT 37% (95% CI 31-42) versus chemo 6% (95% CI 3-12), P<0.0001]. DFS in the HCT cohort was 40% (95% CI 35-45) versus 71% (95% CI 60-79) for chemo, P<0.0001. Similarly, OS favored chemo [HCT 45% (95% CI 40-50)] versus chemo 73% [(95% CI 63-81), P<0.0001]. In multivariable analysis, the sole factor predictive of shorter OS was the administration of HCT [hazard ratio 3.12 (1.99-4.90), P<0.0001]. For younger adults with Ph- ALL, pediatric-inspired chemotherapy had lower TRM, no increase in relapse, and superior overall survival compared to HCT. Am. J. Hematol. 91:322-329, 2016. © 2015 Wiley Periodicals, Inc. Copyright © 2015 Wiley Periodicals, Inc.