Allogeneic Hematopoietic Stem Cell Transplantation Following Reduced-Intensity Conditioning Regimen for Elderly Patients (60 years and older) with Hematological Malignancies Using Unrelated Donors: A Retrospective Study on Behalf of the French Society for Stem Cell Transplantation and Cell Therapies (SFGM-TC)
Authors: El Cheikh Jean , Sfumato Patrick , Fegueux Nathalie , Mohty Mohamad , Yakoub-Agha Ibrahim , Vigouroux Stephane , Beguin Yves , Socie Gerard , Cornillon Jerome , Thepot Sylvain , Bay Jacques-Olivier , Michallet Mauricette , Peffault de Latour Regis 
Published: November 2019

Abstract

Background: Reduced intensity conditioning (RIC) regimen has allowed the extension of allogeneic hematopoietic stem cell transplantation (allo-HSCT) to a previously unreached population of older patients for whom hematologic malignancies aremore common. The use of unrelated donors (UD) in patients aged of 60 years or more has drastically increased in the past few years. To date, there are only limited data on the feasibility and outcomes of UD allo-HSCT in elderly patients (60 years or more). The purpose of the current study is to describe outcomes in a large cohort of patients aged 60 years or older who received a RIC UD allo-HSCT in recent years.
Patients and methods: Between 2008 and 2012, this retrospective multicenter study included 539 consecutive patients aged of 60 years or more (142 aged 65 or more and 9 aged 70 or more) who received a first allo-HSCT for hematological malignancies (351 with myeloid disorders and 188 with lymphoid malignancies) from an UD (HLA matched at HLA-A, -B, -C, -DQ and –DRB1, 10 out of 10 alleles in 95% of cases) after a RIC regimen (Peripheral blood stem cells in 92% of cases) in France. In 85% of the patients, conditioning regimen was fludarabine-based and Graft versus Host Disease (GvHD) prophylaxis consisted of cyclosporine (CSA) plus MMF in 47% of cases and CSA plus methotrexate in 20%. To address the role of age by itself in our population, 2 groups of patients were defined: patients with age at allo-HSCT less than 65 years old ("UD<65 group", n=397) and patients who were aged 65 years or more ("UD ≥ 65 group", n=142). Clinical data were prospectively collected using ProMISe (Project Manager Internet Server), an internet-based data registry system shared by all centers of the French Society of Bone Marrow Transplantation and Cell Therapies (SFGM-TC). This study was approved by the scientific committee of the SFGM-TC and is in accordance with the declaration of Helsinki for clinical research.
Results: Patient characteristics were similar between the 2 groups (UD<65 group and UD ≥ 65 group) for time between diagnosis and allo-HSCT, gender, disease (myeloid versus lymphoid), disease status (complete remission at allo-HSCT versus others), source of stem cells, number of infused total nucleated and CD34 cells, donor age, donor gender, patient/donor sex mismatch, HLA matching, patient/donor CMV (cytomegalovirus) status, the use of antithymocyte globulins (ATG) or TBI-based regimen (2 gray only), and GvHD prophylaxis. Patients in the UD ≥ 65 group received more CD3 cells (p=0.02). The median follow-up was 36 months (range, 0.3-73.5) for UD<65 group and 32 months (range, 0.03-72) for UD≥65 group. During evolution, the cumulative incidence (CI) of grade II–IV acute GvHD was 36% in UD<65 group and 31% in UD≥65 group (p= 0.684) while the CI of chronic GvHD at 2 years was 42% and 35%, respectively (p= 0.334). CI of treatment related mortality (TRM), disease free survival (DFS) and overall survival (OS) were not different between the 2 groups (Table 1). Multivariate analysis for TRM, DFS and OS show that age by itself has no influence.
Conclusion: These data suggest equivalence of outcome between UD<65 group and UD≥65 group after RIC UD allo-HCT in this large cohort of elderly patients ( above 60 years old ) with hematological malignancies. Age by itself thus appears not to be a limitation in this particular population of elderly patients.
Table 1: 2-year cumulative incidence of TRM, DFS and OS Characteristics TRM DFS OS All patients 29% 42% 49% Patients aged less than 65 years (UD<65 group) 28% 41% 49% Patients aged 65 years or more (UD≥65 group) 33% 47% 51% p value 0.350 0.417 0.809

Disclosures
Beguin: Genzyme / Sanofi: Research Funding. Michallet:BMS: Consultancy, Honoraria; Sanofi: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; MSD: Consultancy, Honoraria; Astellas: Consultancy, Honoraria; Hospira: Consultancy, Honoraria.