HLA-Haploidentical Relative and Matched Unrelated Donor Transplant Lead to Similar Survival Outcomes in MDS

Transplantation with an HLA-haploidentical relative donor is associated with similar two-year survival rates compared with transplantation with a matched unrelated donor in patients with myelodysplastic syndromes (MDS), according to a study published in Blood Advances. These findings suggest that in the absence of a matched unrelated donor, transplantation with a haploidentical relative donor is an acceptable treatment route for these patients.

Previous large retrospective studies have been conducted to evaluate outcomes associated with haploidentical donor hematopoietic cell transplantation (HCT) with post-transplant cyclophosphamide (PTCY) in other hematologic malignancies, most notably acute myeloid leukemia, said lead study author Michael Grunwald, MD, of Atrium Health in Charlotte, North Carolina. “However, data regarding haploidentical HCT in MDS, especially using the PTCY approach, have been more limited,” he added. “Since [patients with MDS] tend to be older, they may be less likely to have suitable HLA-matched sibling donors than patients with other hematologic malignancies.”

Dr. Grunwald noted that the use of haploidentical donors, as well as the number of transplants performed for MDS, have been increasing in recent years. “Therefore, achieving a thorough understanding of outcomes with alternative donor HCT for MDS seems to be particularly important,” he said.

The retrospective study by Dr. Grunwald and colleagues included 603 patients with MDS who had undergone HCT with either an HLA-haploidentical relative donor (n=176) or an HLA-matched unrelated donor (n=427) between 2012 and 2017. Patients were identified through the Center for International Blood and Marrow Transplant Research database.

Patients underwent reduced-intensity conditioning. The most commonly used conditioning regimen for each donor type was as follows:

  • HLA-haploidentical relative donor HCT: total-body irradiation plus cyclophosphamide and fludarabine
  • HLA-matched unrelated donor HCT: fludarabine with busulfan or melphalan, and graft-versus-host disease (GVHD) prophylaxis was calcineurin inhibitor with mycophenolate or methotrexate

Prevention of GVHD in the HLA-haploidentical relative donor HCT uniformly consisted of PTCY, calcineurin inhibitor, and mycophenolate. In contrast, GVHD prophylaxis comprised calcineurin inhibitor with mycophenolate or methotrexate in the HLA-matched unrelated donor HCT group.

In the multivariate analysis, HLA-haploidentical relative donor HCT was associated with a higher two-year rate of relapse (48% vs. 33%; hazard ratio [HR] = 1.56; p=.0055) and lower rate of two-year disease-free survival (29% vs. 36%; HR=1.29; p=0.042) compared with HLA-matched unrelated donor HCT (TABLE).

However, there was no difference between the donor types regarding two-year overall survival (46% vs. 44%; HR=0.94; p=0.65). Because of this lack of difference, Dr. Grunwald believes both donor types are acceptable for patients with MDS. “It is important to note that, because donor type was confounded by conditioning regimen and GVHD prophylaxis, this was more a comparison of transplant ‘packages’ rather than a comparison of donor types,” he added. “This suggests that there may be trade-offs with the two approaches, rather than one being clearly superior to the other.”

The use of HLA-haploidentical relative donor HCT was associated with significantly lower acute grade 2-4 GVHD (HR=0.44; p<0.0001) and chronic GVHD (HR=0.36; p<.0001). At two years, the probability of death associated with chronic GVHD was proportionally lower following HLA-haploidentical relative versus HLA-matched unrelated donor HCT (6% vs. 21%, respectively). According to the authors, this negated “any potential survival advantage from better relapse control.”

A limitation of this retrospective study included the investigators’ inability to isolate the donor type from other variables. In addition, while the study was unable to determine who the optimal donor might be for any given patient with MDS, Dr. Grunwald noted that the survival results show that both haploidentical and matched unrelated donors appear to be reasonable choices for patients with MDS undergoing HCT. “Moreover, the outcomes of this study can inform discussions between transplant physicians and patients and between transplant physicians and colleagues,” he added.

Study authors report no relevant conflicts of interest.

Reference

Grunwald MR, Zhang MJ, Elmariah H, et al. Alternative donor transplantation for myelodysplastic syndromes: haploidentical relative and matched unrelated donors. Blood Adv. 2021;5(4):975-983.