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
Matthew J. Wieduwilt, Wendy Stock, Anjali S. Advani, Selina M. Luger, Richard A. Larson, Martin S. Tallman, Frederick R. Appelbaum, Mei-Jie Zhang, Khalid Bo-Subait, Hai-Lin Wang, Vijaya Raj Bhatt, Bhagirathbhai Dholaria, Mary Eapen, Mehdi Hamadani, Omer Jamy, Tim Prestidge, Michael A. Pulsipher, David Ritchie, David A. Rizzieri, Akshay Sharma, Pere Barba, Brenda M. Sandmaier, Marcos de Lima, Partow Kebriaei, Mark R. Litzow, Wael Saber, Daniel J. Weisdorf
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.