Impact of KIR-ligand mismatch on pediatric T-cell acute lymphoblastic leukemia in unrelated cord blood transplantation

Yuta Kawahara, Sae Ishimaru, Junji Tanaka, Shinichi Kako, Masahiro Hirayama, Minoru Kanaya, Hisashi Ishida, Maho Sato, Ryoji Kobayashi, Motohiro Kato, Kumiko Goi, Shoji Saito, Yuhki Koga, Yoshiko Hashii, Koji Kato, Atsushi Sato, Yoshiko Atsuta, Hirotoshi Sakaguchi

Onderzoeksoutput: Bijdrage aan tijdschriftArtikelpeer review

Samenvatting

Currently, allogeneic hematopoietic stem cell transplantation (allo-HSCT) is considered to be indicated for children and adolescents with high-risk or relapsed T-cell acute lymphoblastic leukemia (T-ALL); however, the outcomes are unsatisfactory. Killer cell immunoglobulin-like receptors (KIRs) are the main receptors on natural killer (NK) cells that play an important role in the graft-versus-leukemia effect after allo-HSCT. In allo-HSCT, when the recipient lacks a donor KIR-ligand (KIR-ligand mismatch in the graft-versus-host [GVH] direction), donor NK cells will be activated against recipient cells. KIR-ligand mismatch in the GVH direction improves outcomes after unrelated cord blood transplantation (UCBT) with acute myeloid leukemia, but the effect in T-ALL is unclear. We evaluated the impact of KIR-ligand mismatch in the GVH direction on the transplantation outcomes of children and adolescents with T-ALL who received UCBT. We conducted a retrospective study using a nationwide registry of the Japanese Society for Transplantation and Cellular Therapy. Patients diagnosed with T-ALL, aged 0 to 19 years, and who underwent first UCBT between 1999 and 2017 were included. A total of 91 patients were included in this study. In all, 23 (25.3%) percent of patients had KIR-ligand mismatch in the GVH direction. The 5-year leukemia-free survival (LFS) and overall survival (OS) rates after UCBT were 65.8% and 69.6%, respectively. In a multivariate analysis, KIR-ligand mismatch in the GVH direction was associated with a significant reduction in the relapse rate (hazard ratio [HR], 0.19; P =.002), resulting in better LFS (HR, 0.18; P =.010) and OS (HR, 0.26; P =.048) without increasing non-relapse mortality (NRM; HR, 1.90; P =.264). The cumulative incidence of GVH disease (GVHD) did not differ between patients with and without KIR-ligand mismatch (grade II-IV acute GVHD, 39.1% versus 36.8%, P =.648, grade III-IV acute GVHD, 13.0% versus 11.8%, P =.857, and chronic GVHD, 26.1% versus 22.9%, P =.736, respectively). Furthermore, acute and chronic GVHD were not associated with good patient outcomes. Notably, no relapse was observed in patients who received KIR-ligand mismatched UCBT in complete remission. KIR-ligand mismatch in the GVH direction improved LFS and decreased relapse rates without increasing NRM in children and adolescents with T-ALL who received UCBT, which was not mediated by GVHD.

Originele taal-2Engels
Pagina's (van-tot)598.e1-598.e8
TijdschriftTransplantation and Cellular Therapy
Volume28
Nummer van het tijdschrift9
DOI's
StatusGepubliceerd - sep. 2022

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