Haploidentical Donors as an Option for Patients With Myelodysplastic Syndrome

Results from a Retrospective Multicenter Trial

According to findings from a retrospective multicenter study recently published in Nature: Bone Marrow Transplantation, haploidentical donors (HIDs) may be a comparable treatment option to human leukocyte antigens (HLA)-matched unrelated donors for high-risk myelodysplastic syndrome (MDS) but have a higher incidence of acute graft-versus-host disease (GVHD). 

Claire Michel, MD, University Hospital of Nancy, Nancy, France, and coauthors stated, “The probability of finding a matched sibling donor (MSD) is estimated to be under the classical 30% because of the age of patients with higher-risk MDS and their relatives. For these patients, a matched unrelated donor (MUD) is considered a valid alternative but can take time to identify.” 

In order to expand on possible treatment options for high-risk MDS, Dr Michel et al aimed to assess the efficacy and safety of using HIDs rather than HLA-matched donors for the treatment of high-risk MDS. This evaluation included endpoints of overall survival, progression-free survival, and cumulative incidence of grade 2 to 4 acute GVHD. 

266 patients with high-risk MDS were enrolled in this study. The total number of patients included 218 patients who underwent allogeneic hematopoietic stem cell transplantation using HLA-matched donors (79 HLA-matched sibling donors [MSD] and 139 HLA-matched unrelated donors [MUD]) and 48 patients using HIDs. The median donor age in the HID arm was 64.92 years, while the median was 59 years in the MSD group. 

Results indicated that there were significant differences in terms of conditioning regimen, stem cell sources, in-vivo T-cell depletion, and GVHD prophylaxis between the groups. The overall survival and progression-free survival was significantly higher among patients who received a younger MUD compared to the other groups. However, patients transplanted using HIDs had comparable mortality rates to patients transplanted using MUDs. 

While mortality rates of the HID group were comparable to the MUD group, the incidence of grade 2 to 4 acute GVHD was higher in the HID group, with 37.50% of the HID group experiencing grade 2 to 4 acute GVHD on day 100 versus 18.99% of the MSD group and 34.31% of the MUD group. 6.25% of the haploidentical group and 2.88% of the MUD group experienced secondary graft rejection. Across all groups, the main cause of death was relapse or progression of the original disease (67.27% of MSD, 48.15% of MUD, and 48.65% of HID).

In conclusion, this study suggests that MUDs may provide effective results among high-risk MDS patients compared to MSDs and HIDs. However, the incidence of acute GVHD in HIDs and the variable of age in MUDs should be carefully considered in treatment planning. 

Dr Michel et al concluded that the results of their study “demonstrated similar outcomes after allo-SCT with haploidentical donor (HID) as using an MSD and MUD in high-risk MDS.” 

They added, “The effect of increasing donor age in the MUD group is detrimental to overall survival.”

Source: 

Michel C, Robin M, Morisset S, et al. Outcome after allogeneic stem cell transplantation with haploidentical versus HLA-matched donors in patients with higher-risk MDS. Nature: Bone Marrow Transplantation. Published online February 11, 2023:1-10. doi:https://doi.org/10.1038/s41409-023-01931-7