title: 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.
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.
authors.affiliation: Department of Haematology, Singapore General Hospital, Block 6 level 5, Outram Road, Singapore 169608, Singapore. linn.yeh.ching@sgh.com.sg
authors.forename: Y C
authors.initials: YC
authors.lastname: Linn
authors.forename: C Y
authors.initials: CY
authors.lastname: Phang
authors.forename: T J
authors.initials: TJ
authors.lastname: Lim
authors.forename: S F
authors.initials: SF
authors.lastname: Chong
authors.forename: K K
authors.initials: KK
authors.lastname: Heng
authors.forename: J J
authors.initials: JJ
authors.lastname: Lee
authors.forename: Y
authors.initials: Y
authors.lastname: Loh
authors.forename: W
authors.initials: W
authors.lastname: Hwang
authors.forename: Y T
authors.initials: YT
authors.lastname: Goh
authors.forename: M
authors.initials: M
authors.lastname: Koh
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006650:Histocompatibility Testing; D006801:Humans; D007938:Leukemia / Q000401:mortality / Q000628:therapy*; D008024:Ligands; D008297:Male; D008875:Middle Aged; D019653:Myeloablative Agonists / Q000627:therapeutic use; D011379:Prognosis; D054340:Receptors, KIR / Q000032:analysis*; D012042:Registries; D012189:Retrospective Studies; D035781:Siblings; D012846:Singapore; D016019:Survival Analysis; D055815:Young Adult
chemical_list: D008024:Ligands; D019653:Myeloablative Agonists; D054340:Receptors, KIR