Persistence of recipient human leucocyte antigen (HLA) antibodies and production of donor HLA antibodies following reduced intensity allogeneic haematopoietic stem cell transplantation

Br J Haematol. 2014 Aug;166(3):425-34. doi: 10.1111/bjh.12890. Epub 2014 Apr 18.

Abstract

The effects of reduced intensity conditioning (RIC) on human leucocyte antigen (HLA)-alloimmunization and platelet transfusion refractoriness (PTR) following allogeneic haematopoietic stem cell transplantation (Allo-HSCT) are unknown. We studied HLA-alloantibodies in a cohort of 16 patients (eight HLA-alloimmunized with pre-transplant histories of PTR and eight non-alloimmunized controls) undergoing Allo-HSCT using fludarabine/cyclophosphamide-based RIC. Pre- and post-transplant serum samples were analysed for HLA-antibodies and compared to myeloid, T-cell and bone marrow plasma cell chimaerism. Among alloimmunized patients, the duration that HLA-antibodies persisted post-transplant correlated strongly with pre-transplant HLA-antibody mean fluorescence intensity (MFI) and PRA levels (Spearman's rank correlation = 0·954 (P = 0·0048) and 0·865 (P = 0·0083) respectively). Pre-transplant MFI >10,000 was associated with post-transplant HLA antibody persistence >100 d (P = 0·029). HLA-antibodies persisted ≥100 d in 3/8 patients despite recipient chimaerism being undetectable in all lympho-haematopoietic lineages including plasma cells. Post-transplant de-novo HLA-antibodies developed in three control patients with two developing PTR; the donors for two of these patients demonstrated pre-existing HLA-antibodies of equivalent specificity to those in the patient, confirming donor origin. These data show HLA-antibodies may persist for prolonged periods following RIC. Further study is needed to determine the incidence of post-transplant PTR as a consequence of donor-derived HLA alloimmunization before recommendations on donor HLA-antibody screening can be made.

Keywords: HLA antibodies; allogeneic bone marrow transplantation; platelets.

Publication types

  • Research Support, N.I.H., Intramural

MeSH terms

  • Adolescent
  • Adult
  • Antibody Specificity / immunology
  • Child
  • Female
  • Graft Survival
  • HLA Antigens / immunology*
  • Hematopoietic Stem Cell Transplantation / adverse effects*
  • Humans
  • Isoantibodies / immunology*
  • Male
  • Middle Aged
  • Retrospective Studies
  • Transplantation Conditioning*
  • Treatment Outcome
  • Young Adult

Substances

  • HLA Antigens
  • Isoantibodies