Reduced leukemia relapse through cytomegalovirus reactivation in killer cell immunoglobulin-like receptor-ligand-mismatched cord blood transplantation

Hisayuki Yokoyama, Junya Kanda, Yuta Kawahara, Naoyuki Uchida, Masatsugu Tanaka, Satoshi Takahashi, Makoto Onizuka, Yuma Noguchi, Yukiyasu Ozawa, Yuna Katsuoka, Shuichi Ota, Takanori Ohta, Takafumi Kimura, Yoshinobu Kanda, Tatsuo Ichinohe, Yoshiko Atsuta, Hideki Nakasone, Satoko Morishima

Research output: Contribution to journalArticlepeer-review

Abstract

Cytomegalovirus (CMV) reactivation in cord blood transplantation (CBT) may result in the proliferation and maturation of natural killer (NK) cells. Similarly, a mismatch of the killer cell immunoglobulin-like receptor (KIR)-ligand induces NK cell activation. Therefore, if CMV reactivation occurs in the presence of KIR-ligand mismatch, it might improve CBT outcomes. We assessed the difference in the effect of CMV reactivation in the presence of KIR-ligand mismatch on disease relapse in the graft-versus-host direction. A total of 2840 patients with acute myeloid leukemia, acute lymphoblastic leukemia, myelodysplastic syndrome, and chronic myeloid leukemia were analyzed. Among those with a HLA-Bw4/A3/A11 (KIR3DL-ligand) mismatch, CMV reactivation up to 100 days following CBT had a favorable impact on relapse (18.9% vs. 32.9%, P = 0.0149). However, this effect was not observed in cases without the KIR3DL-ligand mismatch or in those with or without a HLA-C1/C2 (KIR2DL-ligand) mismatch. The multivariate analysis suggested that CMV reactivation had a favorable effect on relapse only in cases with a KIR3DL-ligand mismatch (hazard ratio 0.54, P = 0.032). Moreover, the interaction effect between CMV reactivation and KIR3DL-ligand mismatch on relapse was significant (P = 0.039). Thus, our study reveals the association between KIR-ligand mismatches and CMV reactivation, which will enhance CBT outcomes.

Original languageEnglish
JournalBone Marrow Transplantation
DOIs
Publication statusAccepted/In press - 2021

ASJC Scopus subject areas

  • Hematology
  • Transplantation

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