Donor Age Determines Outcome in Acute Leukemia Patients Undergoing Haploidentical Hematopoietic Cell Transplantation
Authors: Canaani Jonathan , Savani Bipin N. , Labopin Myriam , Huang Xiao Jun , Ciceri Fabio , Arcese William , Koc Yener , Tischer Johanna , Blaise Didier , Gulbas Zafer , Van Lint Maria Teresa , Bruno Benedetto , Mohty Mohamad , Nagler Arnon 
Published: April 2021

Abstract

Introduction
Haploidentical hematopoietic cell transplantation (haplo-HCT) is being increasingly used in acute leukemia patients as an alternative transplant modality when matched sibling or matched unrelated donors are unavailable. As several potential haploidentical relative donors are typically available for a given patient, optimizing donor selection to improve clinical outcome is crucial. The impact of donor age and kinship on the outcome of acute leukemia patients is not clearly established in this setting.
Patients and methods
Using the multinational registry of the acute leukemia working party of the European society for blood and marrow transplantation we retrospectively analyzed the clinical outcomes of adult acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) patients who underwent a first T-cell replete related haplo-HCT between 2005 and 2015.
Results
Our cohort comprised 1270 patients of which 1019 had AML and 251 had ALL. Seven hundred patients were transplanted at age 40 or over and 570 were transplanted at an age of less than 40. Median follow-up for patients in this analysis was 27 months (range 0.6-119 months). In multivariate analysis, patients over the age of 40 were significantly affected by increasing donor age resulting in higher non-relapse mortality (NRM) [Hazard ratio (HR)=1.86, confidence interval (CI) 95%, 1.18-2.94; P=0.007], inferior leukemia-free survival (LFS) (HR=1.59, CI 95%, 1.13-2.24; P=0.007), overall survival (OS) (HR=1.74, CI 95%, 1.22-2.47; P=0.002), and GVHD-free/relapse-free survival (GRFS) (HR=1.6, CI 95%, 1.16-2.22; P=0.004) rates when donors were over the age of 40. Whereas the relationship of the donor to the patient, namely sibling versus child donor, did not impact on patient outcome in a statistically significant manner, our results indicated that in the group of patients over 40 who were transplanted from their children, outcomes were less favorable when donors were over the age of 35. Specifically, this patient subset experienced an increased rate of NRM (HR=1.82, CI 95%, 1.13-2.9; P=0.01), inferior LFS (HR=1.5, CI 95%, 1.05-2.13; P=0.03) as well as inferior OS (HR=1.5, CI 95%, 1.04-2.15; P=0.03). For patients younger than 40 years of age, multivariate analysis revealed that having a donor over the age of 55 was independently associated with a decreased risk for extensive chronic GVHD (HR=0.16, CI 95%, 0.02-0.95; P=0.044) concomitant with a trend for an increased risk of relapse (HR=1.85, CI 95%, 0.97-3.49; P=0.058). The rates of NRM, OS, LFS, acute GVHD, and GRFS were not significantly impacted by donor age in this age group.
Conclusions
Our data establish donor age and kinship as significant determinants of outcome following haplo-HCT for acute leukemia patients with potential implications for future donor selection algorithms in haplo-HCT.

Disclosures
Savani: Jazz Pharmaceuticals: Speakers Bureau. Ciceri: GSK: Other: B-thalassemia gene therapy was developed by Fondazione Telethon and Ospedale San Raffaele and has been inlicenced by GSK that provides funding for the clinical trial, Research Funding. Mohty: Sanofi: Honoraria, Speakers Bureau.