A possible role for the production of multiple HLA antibodies in fatal platelet transfusion refractoriness after peripheral blood progenitor cell transplantation from the mother in a patient with relapsed leukemia

BACKGROUND: There has been controversy over whether HLA alloimmunization is a risk factor for platelet (PLT) transfusion refractoriness (PTR) in hematopoietic peripheral blood progenitor cell transplantation (HPBPCT). STUDY DESIGN AND METHODS: Reported here is a boy with relapsed leukemia who developed fatal PTR after a peripheral blood progenitor cell transplantation (PBPCT) as a second HPBPCT from his mother. To elucidate the cause of PTR, a single‐antigen assay (FlowPRA, One Lambda), a magnetic particles mixed passive hemagglutination test, and anti‐human immunoglobulin‐lymphocyte cytotoxicity test were performed on serum samples of the patient and his mother. RESULTS: Although HLA Class I antibodies were absent in his serum sample before HPBPCT, the serum sample after the first bone marrow transplantation (BMT) reacted weakly with beads coated with multiple HLA Class I molecules. After PBPCT, the positive reaction markedly increased. Although HLA‐B44 antibody emerged transiently after BMT, the apparent generation of antibodies against HLA‐A2 and ‐A24 as well as HLA‐B44 occurred after PBPCT. The continuous appearance of HLA Class I antibodies coincided with the duration of marked PTR after PBPCT. The patient, however, had no antibodies against PLT‐specific glycoproteins. Unidentified HLA Class I–reactive antibodies were detected in maternal serum sample. CONCLUSION: Although the patient appeared to be immunized to allogeneic HLA Class I molecules after BMT, profound HLA alloimmunization might have occurred after PBPCT in this case. It is possible that the administration of large numbers of immunocompetent cells sensitive to alloantigens at PBPCT causes the aberrant and persistent production of the HLA Class I antibodies.