Donor-derived anti-HLA antibodies in a haploidentical hematopoietic cell transplant recipient shortly after transplant.

A pediatric patient with acute myeloid leukemia was referred to our institution for investigational therapy after disease relapse following a mismatched unrelated donor hematopoietic cell transplant (HCT). Prior to second HCT, the patient's serum was negative for antibodies to class I and class II HLA. Eight days after receiving a maternal donor haploidentical transplant, the patient became platelet refractory and highly sensitized to multiple class I HLA. Serum from the patient's mother was positive for the strongest antibodies present in the patient, suggesting the antibodies were donor-derived. Patient sera showed magnified and expanded sensitization over time in the context of 100% donor chimerism and despite undetectable circulating B cells. Escalating sensitization suggests active transfer of rituximab-resistant antibody-producing passenger lymphocytes from a haploidentical donor to a transplant recipient at the time of progenitor cell infusion. Evaluation of donor sensitization status may be a consideration prior to HLA mismatched HCT.
Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Akshay Sharma has received consultant fees from Spotlight Therapeutics, Medexus Inc., Vertex Pharmaceuticals, Sangamo Therapeutics, and Editas Medicine. He is a medical monitor for the RCI BMT CSIDE clinical trial, for which receives financial compensation. He has also received research funding from CRISPR Therapeutics and honoraria from Vindico Medical Education. Dr. Sharma is the St. Jude Children’s Research Hospital site principal investigator for clinical trials of genome editing of sickle cell disease sponsored by Vertex Pharmaceuticals/CRISPR Therapeutics (NCT03745287), Novartis Pharmaceuticals (NCT04443907), and Beam Therapeutics (NCT05456880). The industry sponsors provide funding for the clinical trials, which includes salary support paid to Dr Sharma’s institution. Dr Sharma has no direct financial interest in these therapies. Shane Cross has received consultant fees for Lexicomp (Wolters Kluwer). The other authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
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