Successful engraftment after cord blood transplantation from an HLA‐homozygous donor (homo‐to‐hetero cord blood transplantation) in a primary myelofibrosis patient with broad HLA antibodies

Abstract

BACKGROUND: Donor-specific human leukocyte antigen (HLA) antibodies are a significant risk factor for graft failure in cord blood transplantation (CBT). Although there are several treatments to decrease HLA antibodies, such as platelet transfusion, plasma exchange, rituximab, and bortezomib, their effectiveness has not been established. STUDY DESIGN AND METHODS:We herein report the case of a primary myelofibrosis (PMF) patient with broad HLA antibodies who underwent CBT from an HLAhomozygous donor in which the alleles were matched only in the host-versus-graft direction (homo-tohetero CBT). RESULTS:The cord blood was killer cell immunoglobulin-like receptor (KIR) ligand matched. She received a reduced-intensity conditioning regimen. We used tacrolimus and mycophenolate mofetil as prophylaxis against graft-versus-host disease (GVHD). The neutrophils engrafted on Day 31. A chimerism analysis with fluorescence in situ hybridization of peripheral blood cells showed 99.9% donor type on Day 33. She developed only mild acute skin GVHD and chronic skin GVHD. CONCLUSION: This case indicates the usefulness ofhomo-to-hetero CBT in a patient with broad HLA antibodies with a strong mean fluorescence intensity, which is a significant risk factor for graft failure. Further studies are necessary to determine the risk of GVHD and to elucidate the association between KIR ligand incompatibility and graft failure in homo-to-hetero CBT. ABBREVIATIONS: CBT = cord blood transplantation; HCT = hematopoietic cell transplantation; KIR = killer cell immunoglobulin-like receptor; PMF = primary myelofibrosis; TAC = tacrolimus.From the

Impact of Homozygous Conserved Extended HLA Haplotype on Single Cord Blood Transplantation: Lessons for Induced Pluripotent Stem Cell Banking and Transplantation in Allogeneic Settings

“…As discussed in a previous report [25], KIR ligand mismatch was reported to induce a poorer engraftment failure rate than KIR ligand match in unrelated hematopoietic stem cell transplant [32,37] and in unrelated CBT [38] A recent in vitro experiment showed NK cell alloreactivity against KIR ligandÀmismatched HLA-haploidentical tissue derived from HLA HP homo iPSCs [21], and experimental studies avoiding the alloreactivity of NK cells have been attempted [22,23]. In the field of clinical CBT, this information for HLA homo-hetero CBT are useful for the selection of single cord blood based on HLA matching in CBT, especially in patients with broad donor-specific HLA antibodies to mismatched HLA antigens [39].…”