Allogeneic Hematopoietic Cell Transplantation for Adult Patients with ALL: Current Results and Prognostic Factors. an Analysis from Acute Leukemia Working Party of the EBMT
Authors: Giebel Sebastian , Labopin Myriam , Volin Liisa , Socie Gerard , Yakoub-Agha Ibrahim , Michallet Mauricette , Passweg Jakob R , Milpied Noel-Jean , Chevallier Patrice , Huynh Anne , Marchand Tony , Bourhis Jean-Henri , Fegueux Nathalie , Maertens Johan , Poiré Xavier , Chaganti Sridhar , Rambaldi Alessandro , Mohty Mohamad , Nagler Arnon 
Published: October 2019

Abstract
BACKGROUND: Allogeneic 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.
PATIENTS: 562 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.
RESULTS: The 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.
CONCLUSIONS: Our 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.

Disclosures
Rambaldi: Roche: Honoraria; Novartis: Honoraria; Amgen: Honoraria; Celgene: Research Funding; Pierre Fabre: Honoraria.