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

• Published in: Annals of hematology 2014-09, Vol.93 (9), p.1579-1586
• Main Authors: Michaelis, Sebastian U., Mezger, Markus, Bornhäuser, Martin, Trenschel, Rudolf, Stuhler, Gernot, Federmann, Birgit, Oevermann, Lena, Kanz, Lothar, Handgretinger, Rupert, Bethge, Wolfgang A.
• Format: Article
• Language: English
• Subjects: Adult; Antigens, CD19 - genetics; Antigens, CD19 - metabolism; Blood Group Incompatibility - complications; Blood Group Incompatibility - genetics; CD3 Complex - genetics; CD3 Complex - metabolism; Cell Separation; Female; Haplotypes; Hematologic Neoplasms - genetics; Hematologic Neoplasms - surgery; Hematology; Hematopoietic Stem Cell Transplantation - adverse effects; Hematopoietic Stem Cells - cytology; Hematopoietic Stem Cells - immunology; Hematopoietic Stem Cells - metabolism; Histocompatibility Antigens Class I - genetics; Histocompatibility Testing; Humans; Incidence; Male; Medicine; Medicine & Public Health; Middle Aged; Oncology; Original Article; Receptors, KIR - genetics; Recurrence; Transplantation Conditioning - adverse effects; Transplantation Conditioning - methods; Transplantation, Homologous; Young Adult
• ISSN: 0939-5555; 1432-0584
• DOI: 10.1007/s00277-014-2084-2

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.