Graft-Versus-Leukemia (GVL) Effect After Reduced Intensity Conditioning (RIC) Allogeneic Stem Cell Transplantation (allo-SCT) as Treatment for Acute Myeloid Leukemia (AML): a Survey From the Acute Leukemia Working Party of the EBMT.
Authors: Baron Frederic , Labopin Myriam , Mohty Mohamad , Basara Nadezda , Niederwieser Dietger , Milpied Noel-Jean , Cornelissen J. J. , Malm Claes , Sengeloev Henrik , Blaise Didier , Janssen Jeroen JWM , Petersen Eefke , Socie Gerard , Rocha Vanderson 
Published: October 2019

Abstract
Abstract 3313
Poster Board III-201
RIC allo-SCT has been increasingly used as treatment for AML patients (pts) ineligible for myeloablative allo-SCT. Previous studies have observed a lower risk of relapse in pts who experienced chronic GVHD after RIC allo-SCT versus in those who did not. The objective of the current study was to further investigate the association between chronic GVHD and relapse in a large cohort of pts given RIC allo-SCT as treatment for AML. Data from 1188 AML pts in first or second CR transplanted between 2000 and 2008 following a RIC regimen at EBMT affiliated centers were analyzed. Patients were given PBSC from HLA-identical sibling (MRD, n=879), or from HLA-matched unrelated donors (MUD, n=309). RIC was defined as Busulfan conditioning regimens containing ≤ 8mg/kg total dose, or TBI <6 Gy. Median pt age at transplantation was 55 (range, 18-76) yrs in pts given grafts from MRD, versus 57 (range, 19-72) yrs in those given grafts from MUD. 54 pts had good risk (4.5%), 564 standard-risk (47.5%), and 116 high-risk (9.8%) cytogenetics, while cytogenetic was unknown in 454 pts (38.2%). The impact of chronic GVHD on relapse risk, non-relapse mortality (NRM) and leukemia-free survival (LFS) was assessed by time-dependent multivariate Cox models and in a landmark analysis. Three-yr incidences of relapse, NRM and LFS were 35 ± 2%, 14 ± 2%, and 50 ± 2%, respectively, while 2-yr incidence of chronic GVHD was 49 ± 2%. In a landmark analysis at 18 months after allo-SCT, 5-year relapse rates were 10 ± 2% versus 19 ± 3% for patients with or without chronic GVHD (P=0.04), respectively. In multivariate Cox models, CR2 versus CR1 (P=.003), pt age > 55 yrs (P=.008), alemtuzumab use in the RIC (P=.048), TBI-based RIC (P=.006), high-risk cytogenetics (P=.001), and absence of chronic GVHD (P=.015) were each associated with higher risk of relapse. Factors associated with high NRM were MUD versus MRD (P=.003), grade II-IV acute GVHD (P<.001), and chronic GVHD (P=.002). Factors associated with lower LFS were CR2 versus CR1 (P=.003), pt age > 55 yrs (P=.007), alemtuzumab use in the RIC (P=.012), and high-risk cytogenetics (P=.003). In conclusion, in this cohort of AML patients transplanted in remission, chronic GVHD was associated with a lower risk of relapse while profound in-vivo T cell depletion with alemtuzumab was associated with higher relapse rate suggesting that GVL effects play a role in preventing AML relapse in patients given RIC allo-SCT. Therefore, closed surveillance of patients in this setting not presenting chronic GVHD such as decreasing of immunosuppression should be further investigated.

Disclosures
No relevant conflicts of interest to declare.