KIR haplotype B donors but not KIR-ligand mismatch result in a reduced incidence of relapse after haploidentical transplantation using reduced intensity conditioning and CD3/CD19-depleted grafts.
Natural killer (NK)-cell alloreactivity after allogeneic hematopoietic cell transplantation (HCT) is influenced by the interaction of killer-cell immunoglobulin-like receptors (KIRs) on donor NK cells and human leukocyte antigen (HLA) class I ligands on recipient cells. We investigated the influence of donor KIR haplotype and KIR-ligand mismatch (MM) on relapse in 57 patients with hematologic malignancies receiving haploidentical HCT after reduced intensity conditioning and graft CD3/CD19 depletion. Of the 57 donors, 17 had KIR haplotype A (29.8 %) and 40 had KIR haplotype B (70.2 %). A KIR-ligand MM was found in 34 of 57 patients (59.6 %). There was no difference between donor KIR haplotypes in non-relapse mortality (NRM, p = 0.200) but had a significantly reduced incidence of relapse for patients with a haplotype B donor (p = 0.001). In particular, patients in partial remission (PR) benefited more from a haplotype B graft (p = 0.008) than patients in complete remission (CR, p = 0.297). Evaluating KIR-ligand MM cumulative incidences of relapse (p = 0.680) or NRM (p = 0.579), we found no significant difference. In conclusion, in the setting of reduced intensity conditioning (RIC) and CD3/CD19-depleted haploidentical HCT, we could not confirm the positive data with KIR-ligand MM but observed a significant lower risk of relapse with a KIR haplotype B donor.
Department of General Paediatrics, Haematology and Oncology, University Children's Hospital, 72076, Tuebingen, Germany.
Sebastian U
SU
Michaelis
Markus
M
Mezger
Martin
M
Bornhäuser
Rudolf
R
Trenschel
Gernot
G
Stuhler
Birgit
B
Federmann
Lena
L
Oevermann
Lothar
L
Kanz
Rupert
R
Handgretinger
Wolfgang A
WA
Bethge
D000328:Adult; D018941:Antigens, CD19 / Q000235:genetics / Q000378:metabolism; D001787:Blood Group Incompatibility / Q000150:complications / Q000235:genetics; D017252:CD3 Complex / Q000235:genetics / Q000378:metabolism; D002469:Cell Separation; D005260:Female; D006239:Haplotypes; D019337:Hematologic Neoplasms / Q000235:genetics / Q000601:surgery*; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000276:immunology / Q000378:metabolism; D015395:Histocompatibility Antigens Class I / Q000235:genetics*; D006650:Histocompatibility Testing; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D054340:Receptors, KIR / Q000235:genetics*; D012008:Recurrence; D019172:Transplantation Conditioning / Q000009:adverse effects / Q000379:methods; D014184:Transplantation, Homologous; D055815:Young Adult
D018941:Antigens, CD19; D017252:CD3 Complex; D015395:Histocompatibility Antigens Class I; D054340:Receptors, KIR