Allogeneic Hematopoietic Stem Cell Transplantation in Adolescents and Young Adults with Acute Lymphoblastic Leukemia - Retrospective Dual-Center Study

Background: Adolescents and young adults (AYAs) with acute lymphoblastic leukemia (ALL) are treated with various chemotherapy regimens. Some patients undergo allogeneic hematopoietic stem cell transplantation (HCT) due to high-risk genetic characteristics, chemo-resistant disease (failure to achieve timely measurable residual disease (MRD) negative remissions, or relapse or refractory disease. There is paucity of data on outcomes of AYA ALL patients receiving HCT. Methods: We performed a dual-center analysis of data from MD Anderson Cancer Center (MDACC) and Dana-Farber Cancer Institute (DFCI) to evaluate outcomes of AYA patients who received HCT for Philadelphia-negative (Ph neg) ALL and examined variables that might have an impact on these outcomes. We included all patients who received their first HCT between the ages of 15-40 years between the years 2010-2022. MRD status was evaluated using flow cytometry with a sensitivity of 0.01%. Acute and chronic graft versus host disease (GvHD) were classified according to consensus criteria. The primary endpoint was overall survival (OS), and secondary endpoints included progression rate and non-relapse mortality (NRM). Cox proportional hazards regression analysis was used to evaluate predictors of OS, and Fine and Gray regression for predictors of relapse and NRM. Competing risks were accounted for in analyses pertaining to progression and NRM. Results: A total of 376 Ph neg ALL AYA patients were included in the analysis, 247 from MDACC and 129 from DFCI. The median age at transplant was 25 (range 15-40) years, 39 patients (10%) were aged ≤18 years at time of HCT and 251 (67%) were males.The majority had B-ALL (n=282, 75%), 42 (11%) had complex karyotype and 28 patients (7%) had translocation (4:11). Most patients received either pediatric-inspired (48%) or hyper- cyclophosphamide, vincristine sulfate, doxorubicin, dexamethasone (CVAD) based (42%) frontline induction regimens, and the median time from diagnosis to HCT was 11 (range 2-283) months. At transplant, most patients were in CR1 or CR2 (44% each); 63% of patients achieved MRD negativity prior to HCT. Most patients received an HCT from a matched unrelated donor (MUD) (33%) or a matched sibling donor (MSD) (32%), and most patients received myeloablative conditioning (MAC) (79%) ( Table 1). The cumulative incidence of grade 2-4 acute GvHD and grade 3-4 acute GvHD at 6 months was 37% (95% CI 33%-42%) and 13% (95% CI 10%-17%), respectively. The cumulative in