Nonmyeloablative and Myeloablative Hematopoietic Cell Transplantation for Hematologic Malignancies: Outcomes with HLA-Matched Unrelated Donors Compared to HLA-Identical Sibling Donors.
Authors: Mielcarek Marco , Storer Barry , Kahl Christoph , Sandmaier Brenda M. , Maloney David , Maris Mike B. , Storb Rainer 
Published: April 2020

For most hematologic malignancies treated by myeloablative conditioning, hematopoietic cell transplantation (HCT) from HLA-matched unrelated donors has been associated with greater non-relapse mortality (NRM) and worse overall survival (OS) than that from HLA-identical sibling donors. Poorer outcomes with unrelated grafts are largely related to more frequent or severe graft-versus-host disease (GVHD), and higher rates of graft failure.

In this retrospective analysis we asked whether outcomes of patients with hematologic malignancies who had nonmyeloablative HCT also differed according to donor type. The analysis included all donor/recipient pairs for whom HLA-A, -B, -C, -DR, and DQ allele-level typing information was available. Single allele-level mismatches at HLA class I were allowed. Using these criteria, 308 patients given nonmyeloablative HCT (sibling donors, n=187; unrelated donors, n=121) and 849 patients with myeloablative HCT (sibling donors, n=576; unrelated donors, n=273) between 1997 and 2003 were included. The median ages (range) of nonmyeloablative and myeloablative HCT recipients were 54 (9–72) years and 41 (1–65) years, respectively. The nonmyeloablative regimen consisted of 2 Gy total body irradiation (TBI) with or without fludarabine followed by postgrafting immunosuppression with mycophenolate mofetil and cyclosporine (CSP). Recipients of myeloablative transplants were prepared with different high-dose (TBI-based, 45%; non-TBI-based, 55%) regimens, and the majority (78%) was given methotrexate and CSP for GVHD prophylaxis. G-CSF-mobilized blood was the source of stem cells for all nonmyeloablative transplant recipients, and for 43% of recipients of myeloablative transplants; 57% received bone marrow. Analyses of outcomes used proportional hazard models stratified on diagnosis/disease status, and adjusted for patient age and stem cell source (Table). Our results confirmed that myeloablative HCT from HLA-matched unrelated donors was associated with increased NRM compared to HCT from HLA-identical sibling donors, translating into significantly decreased overall survival for low-risk patients (acute leukemias in first remission, chronic myeloid leukemia in chronic phase, low-risk myelodysplasia). In contrast, a detrimental impact on outcome with unrelated grafts was not appreciable after nonmyeloablative conditioning. Within the limitations of a retrospective analysis, these data suggest that donor type does not influence outcome following nonmyeloablative HCT. Thus, depending on the likely duration and success of a donor search, and the availability of other treatment options, unrelated donor transplantation may be an option for patients who are candidates for nonmyeloablative HCT but who do not have a suitable sibling donor.

OS and NRM with HLA-identical sibling (MSD) vs HLA-matched unrelated (MUD) donors according to type of conditioning Nonmyeloablative Myeloablative N (MSD/MUD) HR (95% CI) P N (MSD/MUD) HR (95% CI) P HR, hazard ratio; CI, confidence interval. HR &lt;1 indicates more favorable, and &gt;1 less favorable outcomes for MUD grafts. Low-Risk OS 21/17 0.23 (0.0–1.9) 0.17 288/152 1.89 (1.3–2.8) 0.001 NRM 0.33 (0.0–2.7) 0.30 2.12 (1.4–3.3) 0.001 High-Risk OS 166/104 1.08 (0.7–1.6) 0.71 288/121 1.09 (0.8–1.5) 0.59 NRM 0.93 (0.5–1.6) 0.80 1.54 (1.0–2.3) 0.05