Wallach's Interpretation of Diagnostic Tests: Pathways to Arriving at a Clinical Diagnosis (994 page)

Shiina T, Inoko H, Kulski JK. An update of the HLA genomic region, locus information and disease associations: 2004.
Tissue Antigens.
2004;64:631.

HLA AND STEM CELL TRANSPLANT

   Definition

   Allogeneic hematopoietic stem cell transplantation (HSCT) has been established as the top treatment of choice for hematologic malignancies and other hematologic or immune disorders. HSCT is also emerging as the most common cell-based immunotherapy to treat solid tumors. Since human leukocyte antigen (HLA), the major histocompatibility complex (MHC) in humans, can elicit an immune response either by presentation of variable peptides or by recognition of polymorphic fragments of foreign HLA molecules, selection of an HLA identical or near-identical donor is preferred. HLA disparity has been associated with graft failure, delayed immune reconstitution, graft versus host disease (GVHD), and mortality.

   HLA is one of the most polymorphic gene systems in the human genome. Consequently, many patients lack HLA-matched donors. In recent years, advances in HLA testing and matching, extensive research on the role of each HLA locus mismatch on clinical outcome, and further knowledge of donor selection factors have made it easier to search for and select a partially matched donor. While the role of donor-specific HLA antibodies (DSA) in solid organ transplantation is well established, their importance in HSCT is only recently emerging. HLA antibody assessment should be incorporated into the HSCT donor selection process.

   Use

   The requirements for HLA testing can be very different based on various transplant protocols and conditioning regimens. A joint agreement, between the transplant program and the HLA lab, detailing the testing algorithm, which is customized to meet the needs of different programs and patient cohorts, is very important. Based on the requirements of ASHI, AABB, CAP, and FACT, a recommended testing algorithm is listed below:

   New transplant candidates:

   High-resolution typing of HLA-A, HLA-B, HLA-C, HLA-DRB1, and HLA-DQB1 loci and intermediate-resolution typing of HLA-DQA1 and -DRB345 loci

   HLA antibody screen and specificity identification using a highly sensitive method, for example, Luminex single antigen–bead (SAB) assay.

   If a patient is identified as having strong DPB1 antibodies at the time of evaluation by Luminex SAB assay, the patient and potential donors should be typed for DPB1 to confirm DPB1 antibody specificity and avoid selecting donors with corresponding DPB1 antigens. Matching DPB1 can also improve the transplant outcome.

   Recent transfusions should be documented. At least 2–3 weeks should pass prior to collecting a new sample for HLA antibody analysis after sensitizing events.

   Related donor typing