Allogeneic HSCT for Patients Aged More Than 55 Years with Myeloid Malignancies: Results of 171 Patients
Authors: Alsuliman Tamim , Harbi Samia , Devillier Raynier , Furst Sabine , Faucher Catherine , Granata Angela , ElCheikh Jean , Chabannon Christian , Castagna Luca , Vey Norbert , Blaise Didier 
Published: October 2019

Abstract
Background:
Incidence of most myeloid malignancies increases with age. Although allogeneic hematopoietic stem cell transplantation (Allo-HSCT) is a curative option for most of myeloid diseases, conventional myeloablative regimens are associated with considerable toxicity in older patients and high rate of non-relapse mortality (NRM). Thus, such standard approach is very rarely performed in the setting of older patients. Recent developments and introduction of reduced intensity\toxicity (RIC/RTC) and non-myeloablative (NMAC) regimens have allowed the extension of Allo-HSCT to these older patients. This study aims to report our experience of Allo-HSCT in patients > 55 years of age.
Patients and Methods:
From 2005 to 2014, 171 patients > 55 years of age with myeloid malignancies underwent first allogeneic HSCT at our center, with a median age of 63 years (56-72 years). Sixty-five patients (38%) had 65 years or more. Data had been double-checked using individual institutional files along with HSCT database of the IPC. Of all patients 117 had AML, 49 had MDS and 5 had MPN. They were conditioned by RIC (120 patients, 70%), RTC (16 patients, 9%) or NMAC (35 patients, 21%) regimens. One hundred and nineteen patients (70%) were transplanted with HLA-identical donor (sibling donor, n=66; unrelated donor; n=53), while 52 patients (30%) received transplantation from alternative donor (mismatched unrelated donor, n=18; cord blood, n=14; haploidentical donor, n=20). We found that 91 patients (53%) have a hematopoietic cell transplantation comorbidity index (HCT-CI) between 0 and 2, while 80 patients (47%) had a HCT-CI ≥ 3. Disease risk index (DRI) was low, intermediate, high and very high in 4 (2%), 108 (63%), 55 (33%) and 4 (2%) patients, respectively.
Results:
NRM at day+100 and 3 years were 7% and 23%, respectively. Cumulative incidences of grade 2-4 acute graft-versus-host disease (GVHD) and chronic GVHD were 20% and 28%, respectively. With a median follow-up of 32 months (3.3-99.5), 3-years cumulative incidence of relapse (CIR), overall survival (OS) and progression free-survival (PFS) were 32%, 52% and 45%, respectively.
Although we found a trend for higher NRM in patients aged above 65 years (< 65 vs. >= 65 years: 20% vs. 28%, p=0.056), no impact of age was found on PFS (< 65 vs. >= 65 years: 44% vs. 46%, p=0.662) and OS (< 65 vs. >= 65 years: 50% vs. 54%, p=0.750). DRI significantly influenced outcome (low + intermediate vs. high + very high: PFS: 53% vs. 28%, p=0.011; OS: 60% vs. 34%, p=0.020) while patients who received NMAC regimens had significantly lower PFS (NMAC vs. RIC vs. RTC: PFS: 26% vs. 50% vs. 50%, p=0.028) and OS (NMAC vs. RIC vs. RTC: PFS: 30% vs. 57% vs. 63%, p=0.031).There were no significant differences of OS or PFS among patients groups classified according to type of donor, sex mismatch, donors' age, donors' sex, donors' CMV antibodies positivity, patients' sex, HCT-CI, disease classification, graft's source or whether they were transplanted before or after 2010.
In multivariate analysis model including conditioning type (NMAC vs. RIC vs. RTC), DRI (low + intermediate vs. high + very high), HCT-CI (0-2 vs. >=3), patients' age (continuous) and donors' type (HLA-identical vs. alternative donor), high/very high DRI as well as the use of NMAC regimens were independent poor predictive factor associated with higher CIR and shorter PFS (HR, 95%CI=1.77, 1.16-2.72; p=0.009 for DRI; HR, 95% CI=1.87, 1.11-3.13; p=0.018 for NMAC) and OS (HR, 95% CI=1.75, 1.11-2.75; p=0.016 for DRI; HR, 95% CI=1.98, 1.14-3.45; p=0.016 for NMAC). Patient's age was associated with higher NRM (HR, 95% CI=1.10, 1.01-1.19; p=0.027).
Conclusion:
Our data shows that though aged patients still generally at a higher risk of NRM, Allo-HSCT using adapted conditioning regimen can provide low NRM and prolonged survival. Beyond the feasibility, disease relapse appears as the major issue after Allo-HSCT. To optimize conditioning regimen for older patients may be a viable option to enhance disease control without raising toxicity. Indeed, the development of RIC/RTC regimens may improve overall outcome of older patients suffering from myeloid diseases. In contrast, truly NMAC regimens may provide insufficient disease control. The optimal conditioning intensity in the setting of older patients with myeloid malignancies remains undefined and should be evaluated in further prospective trials.

Disclosures
No relevant conflicts of interest to declare.