Outcomes following hematopoietic cell transplantation for children, adolescents and young adults with relapsed acute lymphoblastic leukemia.

[BACKGROUND] Allogeneic hematopoietic cell transplantation (HCT) is a common consolidation therapy for recurrent acute lymphoblastic leukemia (ALL), reducing relapse risk but causing significant morbidity, mortality, and potential impairment of growth and development in children, adolescents, and young adults (CAYA). Avoiding or delaying HCT could prevent such complications. New targeted therapies, including CD19 chimeric antigen receptor (CAR) T cells, have increased the number of recurrent ALL patients who might achieve long-term remission without HCT. However, outcomes of delaying HCT beyond second complete remission (CR2) in the modern era remain unclear.

[OBJECTIVE] To compare outcomes of HCT performed in CR2 versus third or later remission (CR3+) in CAYA with ALL.

[METHODS] We retrospectively reviewed CAYA who underwent first HCT for ALL in CR2 (n = 81) or CR3+ (n = 44) at our institution from 2000-2020.

[RESULTS] For all patients, estimated 1-year overall survival (OS), relapse, and nonrelapse mortality (NRM) were 76%, 20.8%, and 9.6%; 3-year estimates were 69%, 30%, and 9.6%, respectively. At 3 years, OS was 77% for CR2 versus 53% for CR3+, and NRM was 6% versus 16%. Adjusted hazard ratios (HR) for CR3+ versus CR2 were: overall mortality HR 1.87 (95% CI, 1.06-3.31), relapse HR 1.28 (95% CI, 0.66-2.50), and NRM HR 2.63 (95% CI, 1.08-6.39).

[CONCLUSIONS] CAYA with ALL undergoing HCT in CR3+ experienced higher NRM and worse survival compared to those transplanted in CR2. Efforts to reduce NRM in multiply relapsed patients are required.