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

Zaina Inam, Division of Hematology, Children's National Hospital, Washington, DC, USA.
Elizabeth Stenger, Aflac Cancer and Blood Disorders Center, Children's Healthcare of Atlanta/Emory University, Atlanta, Georgia, USA.
Tami D. John, Division of Pediatric Hematology, Oncology, Stem Cell and Regenerative Medicine, Stanford University, Palo Alto, California, USA.
Katie Liu, Pediatric Biostatics Core, Department of Pediatrics, Emory School of Medicine, Atlanta, Georgia, USA.
Scott Gillespie, Pediatric Biostatics Core, Department of Pediatrics, Emory School of Medicine, Atlanta, Georgia, USA.
Rikin Shah, Orlando Health - Arnold Palmer Hospital for Children, Orlando, Florida, USA.
Deepakbabu Chellapandian, Cancer and Blood Disorders Institute, Johns Hopkins All Children's Hospital, St Petersburg, Florida, USA.
Monica Bhatia, Division of Pediatric Hematology/Oncology/Stem Cell Transplantation, Columbia University Medical Center, New York, New York, USA.
Sonali Chaudhury, Division of Pediatric Hematology Oncology/Bone Marrow Transplantation, Ann and Robert H Lurie Children's Hospital of Chicago, Chicago, Illinois, USA.
Michael J. Eckrich, Pediatrics Hematology, Oncology, Transplant and Cellular Therapy, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, USA.
Gregory M. Guilcher, Section of Pediatric Hematology, Oncology and BMT, University of Calgary Cumming School of Medicine, Alberta Children's Hospital, Calgary, Alberta, Canada.
Jeanne E. Hendrickson, Department of Pathology and Laboratory Medicine, Emory University, Atlanta, Georgia, USA.
Monica L. Hulbert, Division of Hematology/Oncology, Boston Children's Hospital, Department of Pediatric Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts, USA.
Jennifer J. Jaroscak, Pediatric Hematology/Oncology, Medical University of South Carolina, Charleston, South Carolina, USA.
Kimberly A. Kasow, Division of Pediatric Hematology Oncology, University of North Carolina, Chapel Hill, North Carolina, USA.
Christine Camacho-Bydume, Pediatric Blood and Marrow Transplantation, Hackensack University Medical Center, Hackensack, New Jersey, USA.
Alexander Ngwube, Texas Children's Cancer & Hematology Center, Baylor College of Medicine, Houston, Texas, USA.
Timothy S. Olson, Cell Therapy and Transplant Section, Division of Oncology, Department of Pediatrics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.
Hemalatha G. Rangarajan, Department of Pediatric Hematology Oncology Blood and Marrow Transplant, Nationwide Children's Hospital, Columbus, Ohio, USA.
John T. Horan, Division of Hematology/Oncology, Boston Children's Hospital, Department of Pediatric Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts, USA.
Lakshmanan Krishnamurti, Section of Pediatric Hematology/Oncology/BMT, Department of Pediatrics, Yale University School of Medicine, New Haven, Connecticut, USA.
Shalini Shenoy, Division of Pediatric Hematology/Oncology/Bone Marrow Transplantation, Washington University in St. Louis, St. Louis, Missouri, USA.
Allistair Abraham, George Washington University School of Medicine and Health Sciences, Washington, DC, USA.
Robert Sheppard Nickel, Division of Hematology, Children's National Hospital, Washington, DC, USA.

Document Type

Journal Article

Publication Date

1-12-2026

Journal

American journal of hematology

DOI

10.1002/ajh.70200

Abstract

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.

Department

Pediatrics

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