Impact of HLA Disparity with High-Resolution HLA Typing at HLA-a, -B, -C, and –DRB1 on Engraftment after Reduced Intensity Cord Blood Transplantation in Adults

Introduction

HLA-mismatched unrelated cord blood transplantation (UCBT) is feasible and, in retrospective comparative analyses, allows survival rates similar to conventional unrelated HLA-matched adult-derived grafts. It is clear that the degree of UCB HLA mismatch in patients has a negative effect on outcomes with low-resolution HLA typing at A, B, DR. But the impact of HLA disparity on outcomes with high-resolution HLA typing HLA-A, -B, -C, -DR is unclear.

Patients and Methods

To determine the impact of HLA disparity on outcomes after UCBT, We retrospectively reviewed patients with hematologic malignancies who underwent reduced intensity CBT at Toranomon Hospital from August 2006 and December 2010 consecutively. Patients who had prior history of transplantation, were in poor performance status (ECOG PS >3), had active bacterial or fungal infections at the time of conditioning were excluded. The most frequently used conditioning regimens were fludarabine, alkylating agent (melphalan or busulfan) with total body irradination (TBI), tacrolimus plus mycophenolate mofetil for GVHD prophylaxis. DNAs of 97 pairs were analysed for HLA-A, -B, -C, and -DRB1 based on High Resolution typing. In these cases high resolution typing was carried out retrospectively.

Results

For HLA-A, -B, -C, and -DR based on high resolution typing the following mismatch occurred: no mismatch 2(2%), one mismatch 5(5%), two mismatch 14(14%), three mismatch 32(33%), four mismatch 28(29%), five mismatch 14(14%), six mismatch 2(2%). The number of total nucleated cells and CD34⁺ cells were not significantly different among them.

The cumulative incidence of neutrophil recovery was 83.5% in this study population. It was higher in HLA-B matched group than in HLA-B mismatched group ( 94.2% vs. 78.5% up to day 60, p=0.0044), and in multivariate analysis HLA-B mismatch was independent predictor of engraftment (HR, 0.074; 95%CI, 0.0074-0.74; p=0.026). Among the HLA-A, -C, -DRB1 mismatches, the negative impact of each single HLA allele mismatch was not significant.

The cumulative incidence of grade II to IV aGVHD in this study population was 52.6%. In multivariate analysis, HLA-A mismatch (HR, 10.51; 95%CI, 1.95-56.51; p=0.0061), and HLA-B mismatch (HR, 51.59; 95%CI, 1.05-2520.0; p=0.043) were significantly associated with high incidence of grade II-IV GVHD.

There were no significant difference in the cumulative incidence of TRM, Relapse Rate and OS in this study.

Conclusion

HLA-B allele mismatch was found to have a significant negative impact on engraftment and II-IV aGVHD.