Management of severely HLA-alloimmunized patients who receive allogeneic hematopoietic stem cell transplantation or autologous gene therapy

Transfusion plays a critical role in supportive care for patients who receive allogeneic hematopoietic stem cell transplantation (HSCT) or autologous gene therapy. Platelet (PLT) transfusions are needed for prolonged aplasia periods and blood banks must ensure adequate transfusion management for every patient, even if complicated by severely alloimmunization against human leukocyte antigens (HLA). Today, there still is no consensus on the best strategy to treat severe HLA-alloimmunization or on the mean fluorescence intensity (MFI) threshold to be considered clinically significant in this setting.1

We report on 5 patients (age 17 to 23 years) who received HSCT or autologous gene therapy for different diseases (beta-thalassemia and myelodysplastic syndrome). All patients showed a long transfusion history and severe HLA-alloimunization: HLA-antibody-screen using Luminex technology revealed virtual panel reactive antibodies (vPRA) of 98-100%. Donors were selected, whose platelets lack the HLA antigens against which the patient´s alloantibodies are directed, focusing on HLA antibodies with MFI>5000. PLT transfusion effectivity was frequently controlled by 1-hour posttransfusion increment. When HSCT was scheduled clinicians got into contact with the transfusion medicine team. The blood bank established a list of possible donors in the donor data base, where around 4600 HLA-typed donors are listed and coordinated donor acquisition with the blood donation center.

In aplasia periods regularly 3-4 matched donors are needed weekly. One of the reported patients only needed 13 days until PLT independency after HSCT and received just 8 PLT transfusions, likely based on splenectomy done in childhood. The other patients needed 20 to 28 days to PLT recovery and received 17 to 30 PLT transfusions. There were no major bleeding events.

Platelet transfusion management of severely HLA-alloimmunized patients who receive allogeneic HSCT or autologous gene therapy is resource intensive as it requires proper pre-planning, close communication between hematologists, blood bank and blood donation center and a large HLA-typed donor pool. Without secured access to HLA-selected apheresis platelets innovative and curative therapies of hematologic diseases wouldn´t be possible.

1 Blandin et al.,Platelet transfusion refractoriness and anti-HLA immunization. Transfusion. 2021 Jun;61(6):1700-1704.doi:10.1111/trf.16358

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