Comparable Outcome After Single-Antigen Mismatched Versus Matched Unrelated Donor Hematopoietic Cell Transplantation,

Hematopoietic cell transplantation (HCT) is the treatment of choice for many hematological malignancies and often the only curative option. Despite continuous expansion of unrelated donor registries worldwide, not all patients have a matched donor available and single antigen mismatched donors are used for patients at high risk of relapse or progression. However, it remains unclear whether or not single-antigen mismatched and matched unrelated donor transplantations generate comparable clinical outcomes. Here, we present the results of a unicentre analysis approaching this question.

The outcome of all patients transplanted from unrelated donors between 2000 and 2009 at the University Hospital in Leipzig was analyzed. A total of 206 patients with a median age of 38 (range 18–58) years with acute leukemias, chronic myeloid leukemia, myelodysplastic syndrome or non Hodgkin`s lymphoma were treated with a myeloablative regimen consisting of 12 Gy fractionated total body irradiation (n=189) or busulfan 16mg/m2 (n=17) in combination with cyclophosphamide. All patients received antithymocyte globulin during the conditioning regimen and graft-versus-host prophylaxis with cyclosporine and short course methotrexate. Donors were considered matched according to the typing available at the time of transplantation: Antigen typing in class I and allele typing in class II was available prior to 2006 and 10/10 4 digit HLA typing thereafter. Donors were considered matched if no HLA-antigen mismatch was detected. One hundred and fifty five patients were matched for the HLA loci A, B, C, DRB1 and DQB1 at the antigen level, while 39 patient/donor pairs had a single antigen mismatch and 12 a mismatch of two or more antigens. Disease stage, comorbidity index and Gratwohl score were well balanced in both groups.

After a median follow-up of 49 months, 54% of the 206 patients were alive. Most interestingly, there was no difference in overall survival (OS) at 5 years between HCT with matched and HCT with mismatched donors [52% vs 49% respectively (p=0.48)]. Also similar were event free survival (EFS) at 47% vs. 39% (p=0.44), relapse incidence (RI) 34% vs. 50% (p=0.22) and non-relapse mortality (NRM) 28% vs. 22% (p=0.81) in the matched versus mismatched donors. Acute graft versus host disease (GvHD) grade one or two occurred in 58% of all patients, while 14% had grade three or four and 28% had no signs of acute GvHD. The incidence of GvHD was comparable after antigen mismatched and antigen matched HCT. As expected, there was a significantly better OS, PFS and lower NRM for patients with early (n=104) vs. advanced disease (p=0.02) and patients with high resolution typing vs. low resolution typing (n=99; P=0.04). Even within these subgroups, however, the use of a single antigen mismatched donor did not worsen the results.

In this unicenter analysis a comparable outcome was found after single antigen mismatched HCT compared to matched unrelated donor HCT. An antigen mismatched donor seems to be an acceptable option for patients with high risk malignant disease for whom no fully matched donor is available

No relevant conflicts of interest to declare.