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Abstract: PB2488

Type: Publication Only

Background
Histocompatibility matching of human leukocyte antigens (HLA) between recipient and their family members is essential to identify suitable donors for allogeneic hematopoietic stem cell transplant (AHSCT).  Data on HLA antigen and haplotype frequencies may allow better prediction of the probability of finding HLA-matched donors and consequently enhance the donor search strategy. To our knowledge this is the first haplotype frequency report in Malaysia. 

Aims

This study aims to determine the distribution of HLA antigens and haplotypes in patients who had undergone HLA typing for AHSCT in University of Malaya Medical Centre and to review the outcome of the transplant.

Methods

This retrospective study involves the analysis of HLA typing results of patients and their potential donors who had undergone HLA matching in University of Malaya Medical Centre from 2003 to 2017. The patients and donors’ HLA typing results were collected through their laboratory reports. The Centre routinely tests for HLA antigen/allele group by intermediate resolution solid phase assay.  Only the siblings of the patients were tested in view of the patient require full HLA matched donor for transplantation.  HLA typing for HLA-A, -B, -DR, and -DQ from each patient and potential donor were collected to derive the haplotype present in the patient’s family. The frequency of recurring haplotype was then directly counted and recorded.

Results

A total of 143 patients and their family members (mean no. of siblings = 2.7, SD ± 1.4) were recruited for this study. Majority of the patients were Chinese (62.9%), followed by Malay (29.4%), and Indian (4.9%). While 81 (56.6%) patients found HLA-matched donors, only 42 (29.4%) patients proceeded with AHSCT. Majority of the Malays found a match within their family (69%), followed by Indians (57%), and Chinese (52%). 53.2%, 51.7%, and 25% of Chinese, Malays, and Indians respectively from the matched group proceeded with transplant. No significant association was found between number of siblings screened and number of HLA-matched siblings (p = 0.71). Of the 42 patients who proceeded for AHSCT, 47 haplotypes were successfully derived from 11 patients and their families. Of the 47 haplotypes determined, 12.8% were haplotype HLA-A*33-B*58-DRB1*17-DQB1*02, while HLA-A*01-B*27-DRB1*12-DQB1*05:01, HLA-A*02-B*13-DRB1*15-DQB1*06, HLA-A*02-B*46-DRB1*08-DQB1*06, HLA-A*02-B*60-DRB1*09-DQB1*09, HLA-A*11-B*39-DRB1*08-DQB1*06, HLA-A*24-B*15-DRB1*12-DQB1*07 were each 4.26% respectively. No disease relapse occurred within the haplotype determined group, however one death was reported post-transplant. The most frequent antigens observed from the patients and their families of the transplanted group was HLA-A*11 (31.9%), HLA-B*58 (23.4%), HLA-DRB1*12 (19.1%), and HLA-DRB1*15 (19.1%), and HLA-DQB1*6 (27.7%).

Conclusion

Malaysia is comprised of a multi-ethnic population in which the haplotype distribution may vary among ethnic groups. Though the results suggested the seven most common haplotypes, a larger scale study in healthy population shall be performed to validate the findings.  

Session topic: 22. Stem cell transplantation - Experimental

Keyword(s): Allogeneic hematopoietic stem cell transplant, Haplotype, HLA