Younger donors, better outcomes: The impact of donor age in haploidentical transplantation for acute myeloid leukemia. study conducted on behalf of geth-TC
Year: 2025
Type: conference-abstract
Abstract: INTRODUCTION Haploidentical hematopoietic cell transplantation (haplo-HCT) using post-transplant cyclophosphamide (PTCy)-based prophylaxis has emerged as a safe and effective alternative for patients with acute myeloid leukemia (AML) who lack a suitable HLA-matched related or unrelated donor, and significantly expanded patient's access to transplantation. Donor age has consistently demonstrated a strong association with transplant outcomes. Younger donors have been linked to lower rates of graft-versus-host disease (GVHD) and improved overall survival (OS), making age a key consideration during donor selection. Since patients may have multiple haploidentical donor options with varying chronological ages, understanding the role of donor age in this context, and when PTCY-based prophylaxis is administered, is essential to optimizing outcomes. This multicenter retrospective study evaluates the impact of donor age on outcomes in AML patients undergoing haplo-HCT with PTCy-based prophylaxis. METHODS This registry-based analysis included 274 consecutive AML patients who underwent their first peripheral blood haplo-HCT between 2014 and 2022 at 16 Spanish transplant centers. Donor age was the primary explanatory variable. The main outcomes variables were OS, non-relapse mortality (NRM), cumulative incidence of relapse (CIR) and GVHD incidence. RESULTS Among the 274 patients included, the median age was 53 years (range: 17–74), with 62 (22.6%) aged over 64, 123 (45%) female patients, and 99 (36.8%) adults with a HCT-CI >2. According to the ELN classification, 116 (42.6%) patients had a high-risk AML, and 11 (4.0%) underwent transplantation with active disease. Myeloablative conditioning (MAC) was used in 145 (53%) cases, and all transplants were done with PB. The median donor age was 38 years (range, 13–75). Overall, 49 (17.9%) donors were female, and in 46 (16.4%) cases, female donors provided grafts to male recipients. In univariate analysis, increasing donor age (continuous variable) was associated with worse OS (HR 1.01, p=0.041) and higher NRM (HR 1.02, p=0.009). Receiver operating characteristic analysis identified an optimal donor age cut-off of 30 years for predicting OS. Based on this, the study cohort was divided according to donor age: <30 years (n=85, 31%) and ≥30 years (n=189, 69%). Baseline characteristics were comparable between groups, except for a higher proportion of recipients aged >65 years in the older donor group (27.5% vs. 11.8%; p=0.004). Neutrophil and platelet engraftment kinetics were similar between groups p=0.416 and p=0.948, respectively. Infection rates in the first 180 days post-transplant did not differ significantly: bloodstream infections (50.6% vs. 42.2%, p=0.237), CMV reactivation (60.3% vs. 64.8%, p=1), and CMV disease (10.3% vs. 8.2%, p=0.523). Importantly, patients with younger donors (<30 years) had significantly lower rates of acute GVHD: grade II–IV (Day +100: 3.0% vs. 19.9%, p<0.001) and grade III–IV (1.5% vs. 10.2%, p=0.034). However, moderate-severe chronic GVHD incidence was similar between groups (2-year: 11.7% vs. 11.4%, p=0.49). Relapse rates were comparable (2-year CIR: 18.6% vs. 20.6%; p=0.599), but mortality was lower in recipients of younger donor grafts (28.2% vs. 42.0%; p=0.032), primarily due to reduced NRM (12.9% vs. 24.3%; p=0.016). Consequently, OS was significantly better in the younger donor group (2-year 80.6% vs. 64.3%; p=0.011), with lower NRM (2-year: 11.1% vs. 23.2%; p=0.031). Multivariate analysis (MVA), adjusting for clinically relevant variables [recipient age older than 59 years (vs. younger), high-risk ELN (vs. low and intermediate), HCT-CI >2 (vs. 0-2) and the use of reduced intensity conditioning regimens (vs. MAC)] confirmed that donor age ≥30 years was associated with inferior OS (HR 1.88; p=0.019) and increased NRM risk (HR 2.06; p=0.049). Additional independent predictors of worse OS included patient age >59 years (HR 1.02; p=0.016), high-risk AML (HR 1.60; p=0.029), and comorbidity burden (HCT-CI >2) (HR 2.01; p<0.001). CONCLUSION Donor age is a relevant factor in PB haplo-HCT outcomes for AML. Transplants from donors under 30 years are associated with significantly better OS, primarily due to reduced NRM and lower incidence of grade 2-4 aGVHD incidence. These findings suggest that when multiple haploidentical donors are available, selecting the youngest donor (<30 years) may enhance the probability of haplo-HCT success.
Source: Blood
Authors: Daniel Munárriz Lorca, Estefanía Pérez López, Carlos Martín-Rodriguez, Marta Luque, Albert Esquirol, Carmen Martin, Clara Aparicio, Felipe Peña-Muñoz, Inmaculada Heras, Itziar Oiartzabal Ormategi, Adolfo Sáez Marín, Sara Fernandez-Luis, Juan Domínguez García, Sara Villar, José Luis López Lorenzo, Cynthia Acosta Fleitas, Ana Pilar Gonzalez, Lucia García Mañó, Tamara Torrado, Maria Pascual, Silvia Filafferro, Pascual Balsalobre, Montserrat Rovira, Maria Queralt Salas Gay
Institutions: Hospital Clínic de Barcelona, Complejo Hospitalario de Salamanca, Instituto de Investigación Biomédica de Salamanca, Hospital de Sant Pau, Hospital Universitario Reina Sofía, Institut Català d'Oncologia, Duran i Reynals Hospital, Hospital General Universitario Morales Meseguer, Donostiako Unibertsitate Ospitalea, Hospital Universitario 12 De Octubre, Marqués de Valdecilla University Hospital, Clinica Universidad de Navarra, Universidad de Navarra, Hospital Universitario de Gran Canaria Doctor Negrín, Hospital Universitario Central de Asturias, Hospital Universitario Son Espases, Complexo Hospitalario Universitario A Coruña, Grupo Español de Trasplante Hematopoyético y Terapia Celular, Hospital Regional Universitario de Málaga
Language: English
Subfield: Hematology
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W7108514055
Cites:
Cited by:
Related to: