RBC Alloimmunization Impacts Pediatric Sickle Cell Disease Transplant Outcomes and Transfusion Burden: A STAR Registry Report

Patients with sickle cell disease (SCD) commonly receive red blood cell (RBC) transfusions and can become RBC alloimmunized. This study was designed to investigate if RBC alloimmunization before hematopoietic cell transplant (HCT) was associated with post-HCT outcomes and transfusion support using the multicenter Sickle cell Transplant Advocacy and Research (STAR) retrospective registry. From a cohort of 229 pediatric patients with SCD who underwent human leukocyte antigen (HLA)-matched related donor HCT with myeloablative or reduced intensity conditioning, 40 patients (17%) were RBC alloimmunized pre-HCT. The RBC alloimmunized group had a significantly higher incidence of grade III-IV acute graft-versus-host disease (GVHD) (15% vs. 3.7%, p = 0.013), which remained significant (OR 4.22, 95% CI, 1.19, 14.3; p = 0.027) when controlling for pre-HCT RBC transfusion burden and conditioning intensity. Graft failure occurred in 10% of RBC alloimmunized patients compared with 2.6% of non-alloimmunized patients, p = 0.052. Patients with RBC alloimmunization had lower 5-year severe GVHD-free, rejection-free survival (69% vs. 88%, p = 0.004), which remained significant when controlling for age. Post-HCT patients received a median 3 RBC units (IQR 2, 6) and 11 platelet transfusions (IQR 7, 19). Pre-HCT RBC alloimmunization was associated with a greater requirement for post-HCT platelet transfusions, but not post-HCT RBC units transfused. We postulate that the observed associations of pre-HCT RBC alloimmunization with severe acute GVHD and post-HCT platelet transfusion burden are due to inherent immunologic characteristics that render patients at increased risk of developing multiple immune-mediated complications.