Allogeneic HCT with Reduced Intensity Conditioning Versus Autologous HCT for >55 Years Old Patients with Acute Lymphoblastic Leukemia in First Complete Remission: An Analysis from Acute Leukemia Working Party of the EBMT
Authors: Giebel Sebastian , Labopin Myriam , Gorin Norbert Claude , Milpied Noel , Petersen Eefke , Potter Michael N , Cornelissen Jan J. , Caillot Denis , Niederwieser Dietger , Montserrat Rovira , Jindra Pavel , Meijer Ellen , Maertens Johan , Rambaldi Alessandro , Nagler Arnon , Mohty Mohamad 
Published: October 2019

Abstract
BACKGROUND: The prognosis of patients >55 years old with acute lymphoblastic leukemia (ALL) is poor with reported 5-year survival not exceeding 20%. Disease relapse is a major cause of treatment failure. These patients are usually considered ineligible for standard myeloablative allogeneic hematopoietic cell transplantation (alloHCT) due to frequent presence of co-morbidities and higher rate of toxicities. Alternative strategies include reduced intensity(RIC)-alloHCT or autologous(auto)-HCT. However, the role of these treatment options has not been well established thus far. The aim of the current study was to retrospectively compare results of RIC-alloHCT and autoHCT in ALL >55 years old and to identify factors affecting outcome. Data were derived from the registry of the European Group for Blood and Marrow Transplantation.
PATIENTS: 267 patients treated with RIC-alloHCT from either HLA-identical sibling (n=154) or matched unrelated donor (n=113) and 179 treated with autoHCT in first complete remission between 2000 and 2011 have been included in this analysis. Median age in both groups was 60 (55-74)y and 60 (55-76)y, respectively, while median interval from diagnosis to HCT was 5.9 months and 6.6 months, respectively. The proportion of Ph(+) ALL among those with reported cytogenetics was 71% and 66%, respectively.
RESULTS: With a median follow-up of 33 months, the probability of OS at two years was 44% for RIC-alloHCT and 57% for autoHCT (p=0.02), while LFS rates were 34% and 41%, respectively (p=0.06). The advantage in favor of autoHCT was significant for Ph(-) ALL (OS: 61% vs. 38%, p=0.02; LFS: 54% vs. 21%, p=0.005) while not for Ph(+) ALL (OS: 55% vs. 47%, p=0.6; LFS: 42% vs. 35%, p=0.4).
Relapse incidence at two years was comparable for RIC-alloHCT and autoHCT (42% vs. 48%, p=0.39) while non-relapse mortality was significantly reduced for autoHCT (23% vs. 11%, respectively, p=0.002).
In a multivariate analysis adjusted for recipient age and gender as well as interval from diagnosis to transplantation the use of autoHSCT was independently associated with reduced risk of mortality (HR=0.69, p=0.01), treatment failure (HR=0.76, p=0.03) and non-relapse mortality (HR=0.39; p=0.0004) with no effect on relapse incidence (HR=0.98, p=0.88).
In the RIC-alloHSCT subgroup LFS was negatively affected by female donor/male recipient combination (HR=1.64, p=0.01). LFS rates for both sibling and MUD transplants were comparable (32+/-4% vs. 35+/-5%, p=0.18). The use of peripheral blood cells compared to bone marrow was associated with reduced risk of relapse (HR=0.5, p=0.03). In the autoHSCT setting there was a tendency to higher risk of treatment failure by increasing recipient age (HR=1.05, p=0.06). Other variables including type of conditioning (TBI-based vs. chemotherapy-based) did not affect survival in any of the study cohorts.
CONCLUSIONS: Considering poor overall prognosis of ALL patients >55 years old, results of both RIC-alloHCT and autoHCT appear enhancing and both types of transplantation may be considered valuable treatment options. Potential advantage of autoHCT as suggested by results of our analysis should be further explored including data on disease-related prognostic factors and the status of minimal residual disease. Prospective studies are warranted to define final recommendations.

Disclosures
Niederwieser: Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Gentium: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau.