Decreased Transplant Related Mortality and Better Survival in HLA Matched (12/12 A, B, C, DRB1, DQB1, DPB1) Unrelated Bone Marrow Transplants.

In order to study the association of HLA high resolution typing with outcomes after unrelated bone marrow transplants (UBMT), we have retrospectively analyzed 121 consecutive recipients of unmanipulated UBMT performed in Hôpital Saint-Louis from 1994 to 2002 with a minimum follow-up of 6 months. The median age was 24 years (22 children, 99 adults). Ninety-six patients had malignant disorders (69% leukemias) and 25 had non malignant disorders (bone marrow failure syndromes). High resolution typing was performed in donors and recipients pairs for HLA-A,-B,-C,-DRB1,-DQB1 and-DPB1. According to this typing definition, patients were classified for transplants as 10 out of 10 (<8/10=18 patients, 9/10=32 patients and 10/10=71 patients) and 12 out of 12 (including DPB1 disparities, <9/12=25, 10/12=34, 11/12=48 and 12/12=14 patients). KIR ligand incompatibilities were observed in 19 cases. All transplants were performed using bone marrow cells; TBI and ATG were administered in 80% of cases. Graft versus host disease (GvHD) prophylaxis consisted in CsA+MTX in 90%. Univariable and multivariable analyses, using death as competing event, were performed to study risk factors for outcomes, including number of HLA compatibilities (10 out of 10 and 12 out of 12), KIR incompatibilities and disparities in each locus.

Results: In univariate analysis, we found that patients receiving a graft with less than 10 out of 10 HLA compatibilities (p=0.005) and any disparity in HLA-Class I (p=0.0009) were associated with delayed platelet recovery. Disparities in HLA-B were associated with high incidence of acute GvHD (51% versus 80%, p=0.03) and more importantly, a decreased 180-day transplanted related mortality (TRM) was associated with HLA 12/12 compatibilities instead of HLA 10 out of 10. In fact, TRM was 69% in patients receiving HLA graft <9/12, 41% in 10/12, 38% in 11/12 and 29% in 12/12. Two years survival was also associated with the number of HLA disparities with better survival in those patients receiving a UBMT 12 out of 12 HLA compatible donor. KIR ligand incompatibilities were not associated with any outcomes studied.

In conclusion, decreased TRM and better survival were associated with a compatible unrelated donor using HLA high resolution typing for A, B, C, DRB1, DQB1 and DPB1.