Allogeneic Hematopoietic Cell Transplantation for Adult Patients with ALL: Current Results and Prognostic Factors. an Analysis from Acute Leukemia Working Party of the EBMT

Abstract

BACKGROUNDAllogeneic HCT (alloHCT) with myeloablative conditioning is considered a standard of care for adult patients with high risk acute lymphoblastic leukemia (ALL). However, with improving results of conventional-dose chemotherapy and the introduction of novel agents the indications for alloHCT require re-evaluation, taking into account patient- and procedure-related factors. The aim of this study was to analyze most recent results of alloHCT for adult patients with ALL and to identify factors associated with outcome. PATIENTS562 patients aged 18-55 years (median 35 y) treated with alloHCT from either HLA-matched sibling (n=252) or unrelated (URD, n=310) donors in first complete remission (CR1) during the period 2008-2012 were included in the analysis. The diagnosis was B-ALL (n=430) or T-ALL (n=132). Ph-positive status was present in 225 (40%) cases. RESULTSThe probability of the overall survival (OS) at 2 years was 69%, leukemia-free survival (LFS) - 60%, relapse incidence - 22%, while, non-relapse mortality (NRM) was 17%. The cumulative incidence of grade II-IV acute graft versus host disease (GVHD) and chronic GVHD was 39% and 45%, respectively. In a multivariate analysis, the risk of treatment failure (either relapse or NRM) was increased for patients with high initial tumor burden (WBC >30 x109/L for B-ALL and >100 x109/L for T-ALL, HR=1.45, p=0.01) while, it was reduced for transplantations with conditioning based on total body irradiation (TBI, HR=0.63, p=0.02). The risk of relapse was increased in case of high initial WBC (HR=1.89, p=0.001) and Ph-positive ALL (HR=1.61, p=0.02) while, reduced for TBI-based conditioning (HR=0.48, p=0.004). Finally, the risk of NRM was increased for URD-HCT (HR=2.11, p=0.002) and in case of female donor to male recipient gender combination (HR=1.85, p=0.02). In the URD-HCT setting, a univariate analysis did not reveal significant effects of the level of HLA disparity on outcome. Similarly, other factors, including recipient age, ALL subtype (B vs T), donor/recipient CMV serological status, interval from diagnosis to HCT or the source of stem cells did not affect transplantation outcome. CONCLUSIONSOur registry based study indicates that myeloablative alloHCT performed between 2008-2012 for adult patients with ALL in CR1 result in impressive 2y OS and LFS of 69% and 60%, respectively. Among disease-related risk factors, high initial tumor burden is the strongest predictor of treatment failure. As for procedure-related factors, the choice of conditioning appears most important. Based on our current results, TBI - based regimens should still be strongly recommended. DisclosuresRambaldi:Roche: Honoraria; Novartis: Honoraria; Amgen: Honoraria; Celgene: Research Funding; Pierre Fabre: Honoraria.