Similar Transplant Outcomes for Haplo and MUD Allo-Hcts in AML Patients Achieving CR2: A Study Analyzing 4030 Allo-HCT Recipients from the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation
Authors: Ye Yishan , Labopin Myriam , Yakoub-Agha Ibrahim , Socie Gerard , Blaise Didier , Gedde-Dahl Tobias , Wolfgang Blau Igor , Raiola Anna Maria , Byrne Jennifer , Daguindau Etienne , Labussière-Wallet Hélène , Huynh Anne , Bazarbachi Ali , Nagler Arnon , Brissot Eolia , Li Lin , Luo Yi , Shi Jimin , Mohty Mohamad , Huang He , Ciceri Fabio 
Published: December 2024

Background
Only a minority of relapsing patients will achieve a second complete remission (CR2) and proceed to allogeneic hematopoietic cell transplant (allo-HCT). Donor preference for these patients remains unclear especially with the recent surge of haploidentical (HAPLO) HCTs. In a European Society for Blood and Marrow Transplantation (EBMT) global multi-center, registry-based analysis, we compared the outcomes following allo-HCT from either HAPLO, matched sibling donors (MSD), or 10/10 matched unrelated donors (MUD).
Methods
Data from 4030 adult acute myeloid leukemia patients receiving a first allo-HCT in CR2 from 297 EBMT centers between 2010 and 2022 were analyzed. Transplants from mismatched UD (&lt;10/10), umbilical cord blood, or grafts with ex-vivo manipulation were excluded. Univariate analyses and Cox regression models were used.
Results
Results from 1271 MSD, 1804 MUD, and 955 HAPLO HCTs were analyzed. For the entire cohort, median age was 53 years (range: 18-75). 94% of the patients were diagnosed with de novo AML. A higher proportion of patients with ELN2022 favorable- risk cytogenetics received an allo-HCT from MSD (23%) than from either MUD (20%) or HAPLO (19%) donors. Percentages of positive measurable residual disease (MRD) prior to transplant were comparable among the three cohorts. Peripheral blood was the major graft source (88%) and reduced-intensity conditioning (RIC) was used for approximately half (51%) of the entire cohort. 84% of patients in the HAPLO group received post-transplant cyclophosphamide (PTCy) as graft-versus-host disease (GVHD) prophylaxis. Engraftment rates were higher in the MSD (99%) and MUD (99%) than in the HAPLO (95%) group. Original disease was the major cause of death for the three cohorts.
On univariate analysis, HAPLO HCT was associated with a lower 2-year relapse incidence (RI) (MSD 30.8%, MUD 28.7%, HAPLO 20%) but a higher non-relapse mortality (NRM) (MSD 17.1%, MUD 15.3%, HAPLO 25.7%). The 180-day cumulative incidence of grade II-IV acute GVHD was higher in HAPLO (26.4%) than in MSD (20.5%) or MUD (22.5%) recipients, respectively. Interestingly, the 2-year cumulative incidence of extensive chronic GVHD was higher in the MSD (19.8%) than in MUD (15.6%) or HAPLO (13%) recipients, respectively.
On multivariate analysis, HAPLO (hazard ratio [HR]=1.69, 95% CI 1.25-2.29; p&lt;0.001) and MUD (HR=1.54, 95% CI 1.22-1.95; p&lt;0.001) were associated with higher risk of grade II-IV acute GVHD compared to MSD. There was no significant difference among HAPLO, MSD and MUD allo-HCTs in incidence of overall and extensive chronic GVHD. NRM was higher for HAPLO (HR=1.92, 95% CI 1.36-2.7; p&lt;0.001) and MUD (HR=1.45, 95% CI 1.11-1.89; p=0.006) recipients compared to MSD HCTs. Concerning survival outcomes, HAPLO (HR=1.32, 95% CI 1.04-1.67; p=0.02) and MUD groups (HR=1.22, 95% CI 1.02-1.44; p=0.03) were associated with worse overall survival (OS) compared to MSD, while no significant difference in leukemia-free survival (LFS) or GVHD-free, relapse-free survival (GRFS) was observed between the three cohorts. Importantly, there was no significant difference between HAPLO and MUD recipients with respect to RI, major transplant complications and survival outcomes.
Older patient age i.e., above 50 years was associated with a higher NRM. Older donor age (per 10 years) was associated with a higher NRM and a worse OS, LFS and GRFS. Patients with AML and adverse- or intermediate-risk cytogenetics were associated with higher RI and worse OS, LFS and GRFS compared to those with favorable cytogenetics. Notably, RIC was associated with higher RI (HR=1.3, 95% CI 1.11-1.52; p=0.001), which led to poorer OS, LFS and GRFS compared to myeloablative conditioning.
Conclusions
For AML patients in CR2, HAPLO HCTs resulted in comparable outcomes compared to MUD allo-HCTs while MSD remained the best option, mainly due to lower NRM.