Improved outcomes of acute lymphoblastic leukemia after allogeneic blood or marrow transplantation with highdose post-transplantation cyclophosphamide in the era of more effective pre-transplant therapy.

The therapeutic landscape in acute lymphoblastic leukemia (ALL) has changed dramatically over the last decade. Allogeneic blood or marrow transplantation (alloBMT) has also evolved and remains an important option for consolidation. We assessed the interplay between these factors by analyzing the outcomes of 251 adult ALL (214 B- and 37 T-ALL) patients undergoing alloBMT with post-transplantation cyclophosphamide across two eras: 2008-2014 (ERA1) and 2015-2022 (ERA2). ERA1 patients were younger (median age 45.5 years vs. 50 years, P=0.03), less likely to have a Hematopoietic Stem Cell Transplant-Comorbidity Index score ≥4 (9% vs. 21%, P=0.01), more likely to have measurable residual disease by flow cytometry (20% vs. 9%, P=0.01), and receive myeloablative conditioning (56% vs. 3%, P<0.0001). Overall survival (OS) (Hazard Ratio [HR]: 0.54, P=0.005), relapse-free survival (RFS) (HR: 0.52, P=0.001), and relapse (HR: 0.45, P=0.0005) were improved in ERA2. Non-relapse mortality was similar between eras (HR: 0.88, P=0.73). Significant improvements in OS (HR 0.49, P=0.004) and RFS (HR: 0.46, P=0.0004) in ERA2 due to fewer relapses (HR: 0.38, P=0.0003) were restricted to patients with B-ALL. Irrespective of era, B-ALL patients transplanted in first remission (CR1) had improved RFS (HR: 0.40, P=0.05) if they received pre-transplant blinatumomab. Similarly, Philadelphia chromosome-positve ALL patients transplanted in CR1 who received 2nd or 3rd generation tyrosine kinase inhibitors at diagnosis had improved RFS (HR: 0.29, P=0.0004) and reduced relapse (HR: 0.23, P=0.002) compared to those who received imatinib. Improved alloBMT outcomes in ERA2 in spite of older patient age, increased co-morbidities, and less intensive conditioning were due to reductions in relapse likely driven by changes in pre-transplant therapy.