Effect of missing killer-immunoglobulin-like receptor ligand in recipients undergoing HLA full matched, non-T-depleted sibling donor transplantation: a single institution experience of 151 Asian patients

Bone Marrow Transplant. 2010 Jun;45(6):1031-7. doi: 10.1038/bmt.2009.303. Epub 2009 Nov 9.

Abstract

This retrospective analysis studied the impact of natural killer (NK) alloreactivity based on the missing ligand model, for a cohort of recipients undergoing haemopoietic stem cell transplant without T-cell depletion from HLA full-matched sibling donors. All patients received a uniform myeloablative conditioning regimen and prophylaxis for GVHD. A total of 151 patients were studied, including 62 patients with AML or myelodysplastic syndrome, 42 patients with ALL and 47 patients with CML. We found that 81% of patients had at least one missing KIR-ligand (KIR-L), and HLA-C1 allogroup homozygosity is present in 70% of patients. From multivariate analysis, we observed that the only consistently significant factor that was associated with superior survival was disease stage. Missing KIR-L, whether considering HLA-Bw and HLA-C alleles, without or with HLA-A ligands or narrowing to only HLA-C alleles alone to classify the number of missing KIR-L, did not have any impact on OS or relapse-free survival. This negative finding implies that as the KIR-L composition of recipient is not important in this matched non-T-depleted setting, further immunotherapeutic measures involving adoptive NK cell infusions have to be explored to exploit the benefit of NK alloreactivity for such transplants.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Child
  • Child, Preschool
  • Cohort Studies
  • Female
  • Hematopoietic Stem Cell Transplantation / methods*
  • Histocompatibility Testing*
  • Humans
  • Leukemia / mortality
  • Leukemia / therapy*
  • Ligands
  • Male
  • Middle Aged
  • Myeloablative Agonists / therapeutic use
  • Prognosis
  • Receptors, KIR / analysis*
  • Registries
  • Retrospective Studies
  • Siblings
  • Singapore
  • Survival Analysis
  • Young Adult

Substances

  • Ligands
  • Myeloablative Agonists
  • Receptors, KIR