Outcome of Allogeneic Hematopoietic Cell Transplantation in AML or MDS with a HLA-Mismatched Unrelated Donor: A Single Center Analysis

Introduction: In acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS), allogeneic hematopoietic cell transplantation (HCT) can constitute a curative treatment option. Best results are reported using 10/10 HLA-matched donors, and several reports indicated inferior outcomes because of increased graft versus host disease (GVHD) and non-relapse mortality (NRM) if a HLA-mismatched donor is used.

Methods: Here we present a single center analyses evaluating all patients (pts) with AML or MDS receiving allogeneic HCT with a mismatch unrelated donors (MMUD) between 2004 and 2014.

Results:137 pts were evaluated. Median age was 51 years (range 18-76). For myeloablative conditioning (n=52) the following regimens were used: 12 Gy total body irradiation (TBI) and high-dose cyclophosphamide (n=40), or high-dose busulfan and cyclophosphamide (n=8); for reduced intensity conditioning (n=83) fludarabine with either busulfan (n=27), melphalan (n=6), treosulfan (n=7), cyclophosphamide (=15) or TBI (n=19) was used. Stem cell sources were either peripheral blood (n=134) or bone marrow (n=3). The donor/recipient match was a 9/10 alleleic mismatch in 41% and a 9/10 antigen-mismatch in 59% of cases. All but 21 patients received antithymocyte globuline prior to transplantation for GVHD prophylaxis. Post-transplant immunosuppression consisted of a combination of calcineurine inhibitors with either methotrexate (n=65) or mycophenolate mofetil (n=28). Kaplan-Meier estimated overall survival (OS) for all patients at 1 year was 70% and at 3 years 23%. Cumulative incidence of relapse was 32%. Median follow up of patients alive was 40 months (4-122 month). Engraftment with >500 neutrophils and >25.000 platelets was observed at a median of 20 and 20 days after HCT, respectively. Cumulative incidence of NRM until day 100, 1 year and 3 years was 16%, 27% and 28%, respectively. OS and NRM were not different in pts with allelic or antigen-mismatched donors (OS at 1 year/3 years: 65%/48% versus 48%/33% (p=0,2411), NRM at day 100, 1 year and 3 years: 21%, 24% and 33% versus 20%, 27% and 37% (p=0,6210) ). Acute GvHD mostly occurred at lower grades (grade I 34%, grade II 16%, ≥ grade III 10%). Risk of acute GVHD for patients with an antigen-mismatched donor was not different compared to those with an allelic-mismatched donors (51% versus 42%, p=0,4086).

Conclusion: Stem cell treatment with mismatched donors in allogeneic HCT is a valuable and safe option for pts with missing matched stem cell source. Due to optimized pre- and-posttransplant treatment, satisfactory long term survival can be achieved.