HLA typing for donor-recipient matching in unrelated donor hematopotetic stem cell transplantation

Abstract

ALLOGENEIC HEMATOPOIETIC stem cell transplantation is a clinically important treatment modality in leukemias, inborn errors, and aplastic anemias. The best donor is a sibling sharing both chromosome 6 haplotypes with the recipient. All other donors having only one or zero genetically identical haplotype may be considered only if sharing most HLA specificities. Therefore, determination of HLA antigens constitutes a crucial point in the process of recipient–donor matching. Quality control of this procedure is mandatory to diminish the risk of false typing due to pitfalls in the procedure. The Polish National Bone Marrow Donors Registry was established in 1993. The activity includes: 1. Formal evaluation of requests for alternative donor search for consistency with EBMT and NMDP indications for unrelated donor transplantation. Clinical evaluation of patient status and eligibility for the procedure. 2. Confirmatory typing of the patient and his or her family, search for HLA-matched donor in the worldwide database, and final unrelated donor matching. 3. Recruitment, qualification, and HLA typing of voluntary unrelated donors. The activity of the National Bone Marrow Donor Registry in 1999 to 2000 was analyzed. Altogether, 476 persons were typed for HLA class I antigens with serological techniques (179 patients and 297 family members). In 147 cases, the typing performed in the laboratory of the National Bone Marrow Donors Registry was secondary to serological typing from the home institution of the patient. Discrepant results were found in 37 cases (25%) (Fig. 1). The discrepancies were due to the following: ● Overlooking of one HLA-A or -B antigen in 11 cases ● Overlooking of both HLA-A and -B in 1 case ● False typing of one HLA-A or -B antigen in 15 cases ● Doubtful typing of one HLA-A or -B in 10 cases In these 2 years, 553 persons were typed for HLA class II antigens on the DNA level (172 patients and 381 family members). Of those 65 cases originally typed in eight different Polish institutions were retyped with the use of DNA technique. Discrepant results were found in six cases (9%) (Fig 1). All discrepancies were due to false typing of one HLA-DR antigen (in one case the primary typing was done with a serological and in five cases with a genetic technique). Interestingly, there were no discrepancies in cases where the whole patient’s family was typed for analysis of haplotype segregation. During the last 2 years, the BMDW database was searched for 86 patients. While 17% of patients had no available donor at the required level of matching, the rest of the patients had at least one potential donor found in the world-wide registries, and 33% of them had more than 10 donors due to frequently occurring HLA haplotypes (Fig 2). Cases of suitable recipient–donor pairs were subjected to confirmatory typing (101 recipient-unrelated donor pairs). An unacceptable level of matching was found in 42 cases due to false primary typing or mismatches in two or more allelic specificities, including those not considered at primary matching according to the BMDW listed specificities. Unacceptable matching with regards to four MHC loci (A, B, DR, and DQ) was considered when recipient–donor pairs differed in two specificities at the higher resolution or split level. When five loci were typed (A, B, C, DR, and DQ), up to two mismatches were accepted provided at least one of them was in the C locus. Successful matching at different levels of acceptable compatibility occurred in 59 cases. In 24 cases, HLA A, B, (serologically) and DR DQ (genetically high resolution) specificities were determined, 21 patients were fully matched (8/8 alleles). In 35 cases, HLA A, B (serologically), C (genetically), and DR, DQ (genetically high resolution) resulted in 17 fully matched pairs, 13 pairs with one mismatch (9/10 alleles) and five pairs with two mismatches (8/10 alleles). MLC tests were performed for 46 recipient–donor pairs. A comparison of reactivity in MLC with the presence or absence of HLA class II disparity was done. When DR and DQ were fully matched (26 pairs), low recipient–donor relative response (RR 10%) occurred in 62% of pairs (16/26), DR matched /DQ mismatched (9 pairs) low recipi-