How do I approach ABO‐incompatible hematopoietic progenitor cell transplantation? (CME)

Abstract

H uman leukocyte antigen (HLA) matching is critically important for successful hematopoietic progenitor cell (HPC) transplantation because the rates of engraftment and transplant outcomes are strongly influenced by the degree of match. This is largely because HLA antigens are expressed on immature pluripotent stem cells. In contrast, ABO incompatibility is not a barrier to successful HPC transplantation because ABO blood group antigens are not expressed on pluripotent or early committed HPCs. HLA and ABO antigens are encoded by different genes; thus it is common that potential donors who are fully HLA matched have an ABO incompatibility. Approximately 40 to 50% of HPC transplants are ABO incompatible and are now performed using bone marrow (HPC-M), apheresis-derived peripheral blood progenitor cells (HPCA), and umbilical cord blood (HPC-C) as HPC sources. Three types of ABO incompatibility exist: major, minor, and bidirectional. A total of 20 to 25% of HPC transplants have a major ABO incompatibility, 20 to 25% a minor ABO incompatibility, and up to 5% a bidirectional incompatibility. Each presents a unique set of potential adverse consequences, including early acute hemolysis that can be ameliorated through HPC product processing to remove incompatible red blood cells (RBCs) or plasma (Table 1). In these cases, the recipient must be closely monitored both at the time of the infusion and in the posttransplant period because serious events can occur many days later. Accreditation agencies such as AABB and the Foundation for the Accreditation of Cellular Therapy (FACT) require that all donors be tested for ABO group and D type before the collection of HPC-A or HPC-M and that HPC-C be typed after product processing before cryopreservation. The testing and its required documentation in the medical record need to be done in accordance with institutional standard operating procedures. Current FACT standards also require that “for allogeneic cellular therapy products containing RBCs at the time of administration, a test for ABO group and Rh type shall be performed on the first product collected, or on blood obtained from the donor at the time of the first collection.” At our institution, the donor ABO group and D type is tested as part the donor evaluation process. Additional donor ABO group and D testing is performed on each collection day from blood samples obtained at time of collection. If donor blood sample is not available for a particular collection, confirmatory typing is performed on a product sample on the day of product processing. For all fresh HPC products received from outside facilities, confirmatory ABO group and D testing is performed before further product processing. HPC-C units are received in the frozen state and are not subject to repeat testing.