title: Detrimental effect of natural killer cell alloreactivity in T-replete hematopoietic cell transplantation (HCT) for leukemia patients.
abstract: In hematopoietic cell transplantation (HCT), natural killer cell alloreactivity conferred by inhibitory ligands of killer immunoglobulin-like receptors (iKIRLs) may result in beneficial or detrimental outcomes. More data may contribute to resolution of this complex issue. We analyzed 378 primary allogeneic transplants with T-replete grafts for acute lymphoblastic leukemia (n = 101), acute myeloid leukemia and myelodysplastic syndrome (n = 149), and chronic myeloid leukemia (n = 128). The cohort was divided into 3 groups: in group 1, HLA class I matched at the antigen level (n = 260); in group 2, HLA class I mismatched at the antigen level (n = 57); and in group 3, HLA class I and iKIRLs mismatched (n = 61). One-year overall survival (OS) across groups 1 (59%), 2 (49%), and 3 (30%) was significantly different (P = .002). In contrast to group 2, group 3 had statistically lower OS (P = .05) and event-free survival (P = .01). Relapse and relapse-free mortality appeared to contribute to the low OS in group 3. The detrimental effect of natural killer alloreactivity was also evident when HLA-matched transplants were analyzed for patients lacking iKIRLs. One-year OS in patients lacking the HLA-Cw group 1 or 2 iKIRL was significantly lower than that in patients having the iKIRLs (55% vs 67%, n = 246, P = .01). Our observations indicate that, in T-replete unrelated HCT, iKIRL mismatches and the absence of iKIRLs confer higher risk to patients after HCT.
authors.affiliation: Division of Hematology and HCT, City of Hope National Medical Center and Beckman Research Institute, Duarte, California 91010, USA.
authors.forename: Joel Y
authors.initials: JY
authors.lastname: Sun
authors.forename: Andrew
authors.initials: A
authors.lastname: Dagis
authors.forename: Laima
authors.initials: L
authors.lastname: Gaidulis
authors.forename: Marcia M
authors.initials: MM
authors.lastname: Miller
authors.forename: Roberto
authors.initials: R
authors.lastname: Rodriguez
authors.forename: Pablo
authors.initials: P
authors.lastname: Parker
authors.forename: Auayporn
authors.initials: A
authors.lastname: Nademanee
authors.forename: Peter
authors.initials: P
authors.lastname: Falk
authors.forename: Joseph
authors.initials: J
authors.lastname: Rosenthal
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Forman
authors.forename: David
authors.initials: D
authors.lastname: Senitzer
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D002675:Child, Preschool; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects* / Q000379:methods; D006801:Humans; D007223:Infant; D007694:Killer Cells, Natural / Q000276:immunology*; D007938:Leukemia / Q000628:therapy*; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000628:therapy*; D011971:Receptors, Immunologic / Q000276:immunology*; D054340:Receptors, KIR; D012189:Retrospective Studies; D016019:Survival Analysis; D014184:Transplantation, Homologous / Q000009:adverse effects / Q000379:methods
chemical_list: D011971:Receptors, Immunologic; D054340:Receptors, KIR