Better Outcome Following Younger Haploidentical Donor Versus Older Matched Unrelated Donor Transplant for Patients with Acute Myeloid Leukemia in First Remission: A Study from the Global Committee and Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation
Authors: Ye Yishan , Ferhat Berland Allain Thibeault , Labopin Myriam , Chen Jia , Wu Depei , Blaise Didier , Angelucci Emanuele , Forcade Edouard , Huang Xiao-Jun , Yakoub-Agha Ibrahim , Salmenniemi Urpu , Chevallier Patrice , Bazarbachi Ali , Nagler Arnon , Brissot Eolia , Li Lin , Luo Yi , Zhao Yanmin , Ciceri Fabio , Huang He , Mohty Mohamad , Gorin Norbert Claude 
Published: December 2024

Background
Matched sibling donor (MSD) remains to date the first choice for allogeneic hematopoietic cell transplantation (allo-HCT). Haploidentical donors (HAPLO) have surged up as important alternative whose therapeutic effects might be similar to 10/10 matched unrelated donor (MUD). Donor age has been associated with worse outcomes after allo-HCT mainly due to higher rate of graft-versus-host disease (GvHD). We compared in an EBMT global multi-center registry-based analysis the outcomes following allo-HCT from younger HAPLO or older MUD.
Methods
Data of 4205 adult AML patients receiving a first allo-HCT in CR1 from between 2010 and 2022 were analyzed. Transplants from mismatched UD (&lt;10/10) were excluded. Statistical analysis included univariable and multivariable analysis (MVA) adjust for potential confounding factors using a Cox proportional-hazards regression model for main outcomes.
Results
Data of 2651 patients receiving younger HAPLO (15-40 years old(yo)) and 1554 patients receiving older MUD (40-65yo) HCTs were analyzed. For the entire cohort, median patient age was 55.6y (range: 18-75), and the disease risk classification distribution was similar between the two groups according to the ELN 2022 criteria. More patients in the younger HAPLO group received myeloablative conditioning (65%) than in the older MUD group (50%, p&lt;0.001). For GVHD prophylaxis, post-transplant cyclophosphamide was the major regimen for younger HAPLO (66%) while ATG served as backbone for older MUD (92%). The median follow-up was 2.5 years (interquartile range, IQR= 2.3 - 2.6) for younger HAPLO and 3.7 years (IQR= 3.3 - 4) for older MUD.
We found that the proportion of patients with a Karnofsky &gt;=90 was higher for older MUD. To avoid any bias due to this interaction between variable, we separated the analysis according to the Karnofsky score (&gt; =90 and &lt;90) during multivariate analysis.
On multivariable analysis, for patients with Karnofsky score &gt; =90, older MUD was associated with higher RI (hazard ratio [HR]=1.36, 95% CI 1.14-1.63; p=0.001, younger HAPLO as reference) and higher extensive cGVHD incidence (HR=1.73, 95% CI 1.34-2.24; p&lt;0.001) compared to younger HAPLO, leading to worse LFS (HR=1.16, 95% CI 1.01-1.33; p=0.032). For patients with Karnofsky score &lt;90, older MUD was associated with higher overall (HR=1.44, 95% CI 1.05-1.98; p=0.025) and extensive cGVHD incidences (HR=1.88, 95% CI 1.18-2.99; p=0.008). Although older MUD was associated with better NRM compared to younger HAPLO (HR=0.72, 95% CI 0.52-1; p=0.048), no significant difference was between the two groups concerning LFS and OS.
Additionally, adverse ELN2022 cytogenetics was associated with higher RI, poorer LFS and OS. Older patient age (per 10 years) was associated with higher NRM, which led to inferior LFS and OS, for patients with Kanorfsfy score &lt;90 and &gt;=90.
Conclusions
Younger haploidentical donors might be superior to older matched unrelated donors AML patients allografted in CR1 due to lower RI and extensive cGVHD incidences, especially for patients with Karnofsky &gt;=90.