Early Cytomegalovirus Reactivation and Expansion of CD56brightCD16dim/−DNAM1+ Natural Killer Cells Are Associated with Antileukemia Effect after Haploidentical Stem Cell Transplantation in Acute Leukemia

Ji Eun Jang, Doh Yu Hwang, Haerim Chung, Soo Jeong Kim, Ju In Eom, Hoi Kyung Jeung, Jaewoo Song, Jin Seok Kim, June Won Cheong, Yoo Hong Min

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Cytomegalovirus (CMV) infection is a major complication after allogeneic hematopoietic stem cell transplantation but is suggested to exert a strong antileukemia effect in part due to alterations in the composition of natural killer (NK) cells. We evaluated the impact of early CMV reactivation and changes in NK cell subset recovery on relapse rate and survival after haploidentical stem cell transplantation (haploSCT) for acute leukemia. Fifty patients with acute leukemia who received haploSCT were analyzed. Expression of T cells and specific receptors (NKG2A, NKG2D, DNAM1, and CD57) on circulating NK cells (CD56brightCD16dim/ or CD56dimCD16+ cells) was serially measured using multiparametric flow cytometry. CMV reactivation during the first 100 days was observed in 41 patients (82%) at a median of 23 days after haploSCT. The incidence of acute graft-versus-host disease (GVHD) and chronic GVHD tended to be higher in patients with CMV reactivation, although this difference was not statistically significant. Multivariate analysis showed that CMV reactivation (P =.011) and a dose of infused T cells > 3.2 × 108/kg (P =.027) were independent predictors of a reduced relapse risk and only CMV reactivation (P =.029) was an independent predictor of improved leukemia-free survival. CD56brightCD16dim/−DNAM1+NK cell counts increased from day 30 to 90 in patients with CMV reactivation but decreased after day 30 in patients without CMV reactivation. An increase in CD56brightCD16dim/−DNAM1+ NK cells was not associated with the occurrence of chronic GVHD but was associated with a reduced cumulative relapse rate (16.4% versus 58.0%, P =.019). Multivariate analysis indicates that an increase in the CD56brightCD16dim/−DNAM1+NK cell count was an independent predictor of reduced relapse risk. Our study demonstrates a significant correlation between low relapse rates and CMV reactivation as well as the recovery of CD56brightCD16dim/−DNAM1+ NK cells, providing valuable information for understanding the plausible immunologic mechanism of the graft-versus-leukemia effect.

Original languageEnglish
Pages (from-to)2070-2078
Number of pages9
JournalBiology of Blood and Marrow Transplantation
Volume25
Issue number10
DOIs
Publication statusPublished - 2019 Oct

Fingerprint

Stem Cell Transplantation
Cytomegalovirus
Natural Killer Cells
Leukemia
Recurrence
Graft vs Host Disease
Multivariate Analysis
Cell Count
Hematopoietic Stem Cell Transplantation
Cytomegalovirus Infections
T-Cell Antigen Receptor
Flow Cytometry
Survival Rate
T-Lymphocytes
Transplants
Survival
Incidence

All Science Journal Classification (ASJC) codes

  • Hematology
  • Transplantation

Cite this

Jang, Ji Eun ; Hwang, Doh Yu ; Chung, Haerim ; Kim, Soo Jeong ; Eom, Ju In ; Jeung, Hoi Kyung ; Song, Jaewoo ; Kim, Jin Seok ; Cheong, June Won ; Min, Yoo Hong. / Early Cytomegalovirus Reactivation and Expansion of CD56brightCD16dim/−DNAM1+ Natural Killer Cells Are Associated with Antileukemia Effect after Haploidentical Stem Cell Transplantation in Acute Leukemia. In: Biology of Blood and Marrow Transplantation. 2019 ; Vol. 25, No. 10. pp. 2070-2078.
@article{55c8a620c28f46569319d78583b3f54d,
title = "Early Cytomegalovirus Reactivation and Expansion of CD56brightCD16dim/−DNAM1+ Natural Killer Cells Are Associated with Antileukemia Effect after Haploidentical Stem Cell Transplantation in Acute Leukemia",
abstract = "Cytomegalovirus (CMV) infection is a major complication after allogeneic hematopoietic stem cell transplantation but is suggested to exert a strong antileukemia effect in part due to alterations in the composition of natural killer (NK) cells. We evaluated the impact of early CMV reactivation and changes in NK cell subset recovery on relapse rate and survival after haploidentical stem cell transplantation (haploSCT) for acute leukemia. Fifty patients with acute leukemia who received haploSCT were analyzed. Expression of T cells and specific receptors (NKG2A, NKG2D, DNAM1, and CD57) on circulating NK cells (CD56brightCD16dim/ – or CD56dimCD16+ cells) was serially measured using multiparametric flow cytometry. CMV reactivation during the first 100 days was observed in 41 patients (82{\%}) at a median of 23 days after haploSCT. The incidence of acute graft-versus-host disease (GVHD) and chronic GVHD tended to be higher in patients with CMV reactivation, although this difference was not statistically significant. Multivariate analysis showed that CMV reactivation (P =.011) and a dose of infused T cells > 3.2 × 108/kg (P =.027) were independent predictors of a reduced relapse risk and only CMV reactivation (P =.029) was an independent predictor of improved leukemia-free survival. CD56brightCD16dim/−DNAM1+NK cell counts increased from day 30 to 90 in patients with CMV reactivation but decreased after day 30 in patients without CMV reactivation. An increase in CD56brightCD16dim/−DNAM1+ NK cells was not associated with the occurrence of chronic GVHD but was associated with a reduced cumulative relapse rate (16.4{\%} versus 58.0{\%}, P =.019). Multivariate analysis indicates that an increase in the CD56brightCD16dim/−DNAM1+NK cell count was an independent predictor of reduced relapse risk. Our study demonstrates a significant correlation between low relapse rates and CMV reactivation as well as the recovery of CD56brightCD16dim/−DNAM1+ NK cells, providing valuable information for understanding the plausible immunologic mechanism of the graft-versus-leukemia effect.",
author = "Jang, {Ji Eun} and Hwang, {Doh Yu} and Haerim Chung and Kim, {Soo Jeong} and Eom, {Ju In} and Jeung, {Hoi Kyung} and Jaewoo Song and Kim, {Jin Seok} and Cheong, {June Won} and Min, {Yoo Hong}",
year = "2019",
month = "10",
doi = "10.1016/j.bbmt.2019.06.008",
language = "English",
volume = "25",
pages = "2070--2078",
journal = "Biology of Blood and Marrow Transplantation",
issn = "1083-8791",
publisher = "Elsevier Inc.",
number = "10",

}

Early Cytomegalovirus Reactivation and Expansion of CD56brightCD16dim/−DNAM1+ Natural Killer Cells Are Associated with Antileukemia Effect after Haploidentical Stem Cell Transplantation in Acute Leukemia. / Jang, Ji Eun; Hwang, Doh Yu; Chung, Haerim; Kim, Soo Jeong; Eom, Ju In; Jeung, Hoi Kyung; Song, Jaewoo; Kim, Jin Seok; Cheong, June Won; Min, Yoo Hong.

In: Biology of Blood and Marrow Transplantation, Vol. 25, No. 10, 10.2019, p. 2070-2078.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Early Cytomegalovirus Reactivation and Expansion of CD56brightCD16dim/−DNAM1+ Natural Killer Cells Are Associated with Antileukemia Effect after Haploidentical Stem Cell Transplantation in Acute Leukemia

AU - Jang, Ji Eun

AU - Hwang, Doh Yu

AU - Chung, Haerim

AU - Kim, Soo Jeong

AU - Eom, Ju In

AU - Jeung, Hoi Kyung

AU - Song, Jaewoo

AU - Kim, Jin Seok

AU - Cheong, June Won

AU - Min, Yoo Hong

PY - 2019/10

Y1 - 2019/10

N2 - Cytomegalovirus (CMV) infection is a major complication after allogeneic hematopoietic stem cell transplantation but is suggested to exert a strong antileukemia effect in part due to alterations in the composition of natural killer (NK) cells. We evaluated the impact of early CMV reactivation and changes in NK cell subset recovery on relapse rate and survival after haploidentical stem cell transplantation (haploSCT) for acute leukemia. Fifty patients with acute leukemia who received haploSCT were analyzed. Expression of T cells and specific receptors (NKG2A, NKG2D, DNAM1, and CD57) on circulating NK cells (CD56brightCD16dim/ – or CD56dimCD16+ cells) was serially measured using multiparametric flow cytometry. CMV reactivation during the first 100 days was observed in 41 patients (82%) at a median of 23 days after haploSCT. The incidence of acute graft-versus-host disease (GVHD) and chronic GVHD tended to be higher in patients with CMV reactivation, although this difference was not statistically significant. Multivariate analysis showed that CMV reactivation (P =.011) and a dose of infused T cells > 3.2 × 108/kg (P =.027) were independent predictors of a reduced relapse risk and only CMV reactivation (P =.029) was an independent predictor of improved leukemia-free survival. CD56brightCD16dim/−DNAM1+NK cell counts increased from day 30 to 90 in patients with CMV reactivation but decreased after day 30 in patients without CMV reactivation. An increase in CD56brightCD16dim/−DNAM1+ NK cells was not associated with the occurrence of chronic GVHD but was associated with a reduced cumulative relapse rate (16.4% versus 58.0%, P =.019). Multivariate analysis indicates that an increase in the CD56brightCD16dim/−DNAM1+NK cell count was an independent predictor of reduced relapse risk. Our study demonstrates a significant correlation between low relapse rates and CMV reactivation as well as the recovery of CD56brightCD16dim/−DNAM1+ NK cells, providing valuable information for understanding the plausible immunologic mechanism of the graft-versus-leukemia effect.

AB - Cytomegalovirus (CMV) infection is a major complication after allogeneic hematopoietic stem cell transplantation but is suggested to exert a strong antileukemia effect in part due to alterations in the composition of natural killer (NK) cells. We evaluated the impact of early CMV reactivation and changes in NK cell subset recovery on relapse rate and survival after haploidentical stem cell transplantation (haploSCT) for acute leukemia. Fifty patients with acute leukemia who received haploSCT were analyzed. Expression of T cells and specific receptors (NKG2A, NKG2D, DNAM1, and CD57) on circulating NK cells (CD56brightCD16dim/ – or CD56dimCD16+ cells) was serially measured using multiparametric flow cytometry. CMV reactivation during the first 100 days was observed in 41 patients (82%) at a median of 23 days after haploSCT. The incidence of acute graft-versus-host disease (GVHD) and chronic GVHD tended to be higher in patients with CMV reactivation, although this difference was not statistically significant. Multivariate analysis showed that CMV reactivation (P =.011) and a dose of infused T cells > 3.2 × 108/kg (P =.027) were independent predictors of a reduced relapse risk and only CMV reactivation (P =.029) was an independent predictor of improved leukemia-free survival. CD56brightCD16dim/−DNAM1+NK cell counts increased from day 30 to 90 in patients with CMV reactivation but decreased after day 30 in patients without CMV reactivation. An increase in CD56brightCD16dim/−DNAM1+ NK cells was not associated with the occurrence of chronic GVHD but was associated with a reduced cumulative relapse rate (16.4% versus 58.0%, P =.019). Multivariate analysis indicates that an increase in the CD56brightCD16dim/−DNAM1+NK cell count was an independent predictor of reduced relapse risk. Our study demonstrates a significant correlation between low relapse rates and CMV reactivation as well as the recovery of CD56brightCD16dim/−DNAM1+ NK cells, providing valuable information for understanding the plausible immunologic mechanism of the graft-versus-leukemia effect.

UR - http://www.scopus.com/inward/record.url?scp=85068365561&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85068365561&partnerID=8YFLogxK

U2 - 10.1016/j.bbmt.2019.06.008

DO - 10.1016/j.bbmt.2019.06.008

M3 - Article

C2 - 31212079

AN - SCOPUS:85068365561

VL - 25

SP - 2070

EP - 2078

JO - Biology of Blood and Marrow Transplantation

JF - Biology of Blood and Marrow Transplantation

SN - 1083-8791

IS - 10

ER -