Delayed NK Cell Reconstitution and Reduced NK Activity Increased the Risks of CMV Disease in Allogeneic-Hematopoietic Stem Cell Transplantation.

Ki Hyun Park,Ji Hyeong Ryu,Hyunjoo Bae,Hyeyoung Lee,Joo Hee Jang,Byung Sik Cho,Sojeong Yun,Eun-Jee Oh,Hee-Je Kim,Kyungja Han

doi:10.3390/ijms21103663

Abstract

Cytomegalovirus (CMV) infection has a significant impact in patients after allogeneic hematopoietic stem cell transplantation (HSCT). We investigated natural killer (NK) cell reconstitution and cytotoxic/cytokine production in controlling CMV infection, especially severe CMV disease in HSCT patients. Fifty-eight patients with acute myeloid leukemia (AML) who received allo-HSCT were included. We monitored NK reconstitution and NK function at baseline, 30, 60, 90, 120, 150, and 180 days after HSCT, and compared the results in recipients stratified on post-HSCT CMV reactivation (n = 23), non-reactivation (n = 24) versus CMV disease (n = 11) groups. The CMV disease group had a significantly delayed recovery of CD56dim NK cells and expansion of FcRγ-CD3ζ+NK cells started post-HSCT 150 days. Sequential results of NK cytotoxicity, NK cell-mediated antibody-dependent cellular cytotoxicity (NK-ADCC), and NK-Interferon-gamma (NK-IFNγ) production for 180 days demonstrated delayed recovery and decreased levels in the CMV disease group compared with the other groups. The results within 1 month after CMV viremia also showed a significant decrease in NK function in the CMV disease group compared to the CMV reactivation group. It suggests that NK cells’ maturation and cytotoxic/IFNγ production contributes to CMV protection, thereby revealing the NK phenotype and functional NK monitoring as a biomarker for CMV risk prediction, especially CMV disease.

Highlights

Hematopoietic stem cell transplantation (HSCT) is a well-established treatment for patients with acute myeloid leukemia (AML) [1]
HSCT from matched unrelated donor (MUD) and familial mismatched donor (FMD) has demonstrated a higher incidence of CMV viremia and delayed immune constitution compared to HSCT from human leukocyte antigen (HLA)-matched related donors, suggesting the employment of novel approaches, such as immunotherapy or more aggressive CMV prophylaxis, in these patients [3]
We monitored the sequential data of 58 AML patients who received HSCT from MUD or FMD

Summary

Introduction

Hematopoietic stem cell transplantation (HSCT) is a well-established treatment for patients with acute myeloid leukemia (AML) [1]. The range of CMV infection after HSCT can be different because HSCT patients have diverse CMV serostatus, different CMV prophylaxis, conditioning methods, genetic polymorphism, and inconstant post-HSCT immune reconstitution against CMV infection [5,7,9,11,12]. Considering these differences, CMV-specific immunity plays a vital role in controlling CMV reactivation and disease development. Verification and monitoring of the patient’s immune cells can be an important tool for the defense of CMV infection

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