Original Article

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Blood Res 2014; 49(3):

Published online September 25, 2014

https://doi.org/10.5045/br.2014.49.3.162

© The Korean Society of Hematology

Influence of NK cell count on the survival of patients with diffuse large B-cell lymphoma treated with R-CHOP

Joong-Keun Kim, Joo-Seop Chung*, Ho-Jin Shin, Moo-Kon Song, Ji-Won Yi, Dong-Hun Shin, Dae-Sung Lee, and Sung-Min Baek

Department of Hematology-Oncology, Pusan National University Hospital Medical Research Institute, Busan, Korea.

Correspondence to : Correspondence to Joo-Seop Chung, M.D. Department of Hematology-Oncology, School of Medicine, Pusan National University, 1-10 Ami-dong, Gudeok-ro 179, Seo-gu, Busan 602-739, Korea. Tel: +82-51-240-7225, Fax: +82-51-254-3127, Hemon@pusan.ac.kr

Received: May 12, 2014; Revised: June 13, 2014; Accepted: July 23, 2014

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Background

Although adding rituximab to the chemotherapy regimen of cyclophosphamide, vincristine, doxorubicin, and prednisone (R-CHOP) has improved clinical outcomes of patients with diffuse large B-cell lymphoma (DLBCL), several recent studies have shown that the effect of rituximab is dominantly in the non-germinal center (non-GC) subtype compared to the germinal center (GC) subtype. Natural killer (NK) cell count, a surrogate marker of immune status, is associated with clinical outcomes in DLBCL patients in the rituximab era. We investigated whether the impact of NK cells on clinical outcomes differed according to the immunophenotype of DLBCL.

Methods

This study analyzed 72 DLBCL patients treated with R-CHOP between January 2010 and January 2014.

Results

Low NK cell counts (<100/µL) were associated with poor progression-free survival (PFS) and overall survival (OS) compared to high NK cell counts. In multivariate analysis, low NK cell count was an independent prognostic factor for PFS and OS. However, survival did not significantly differ between the GC and non-GC subtypes. We examined the clinical influence of NK cells according to the immunophenotype and found that low NK cell counts were significantly associated with poor PFS and OS in non-GC cases, but not in GC cases.

Conclusion

Low NK cell counts at diagnosis are associated with poor clinical outcomes in DLBCL patients treated with R-CHOP therapy. However, the impact is significant only in non-GC subtype DLBCL, not in the GC subtype.

Keywords Natural killer cell coun, Diffuse large B-cell lymphoma, Rituximab, Germinal center type, Non-germinal center type

Article

Original Article

Blood Res 2014; 49(3): 162-169

Published online September 25, 2014 https://doi.org/10.5045/br.2014.49.3.162

Copyright © The Korean Society of Hematology.

Influence of NK cell count on the survival of patients with diffuse large B-cell lymphoma treated with R-CHOP

Joong-Keun Kim, Joo-Seop Chung*, Ho-Jin Shin, Moo-Kon Song, Ji-Won Yi, Dong-Hun Shin, Dae-Sung Lee, and Sung-Min Baek

Department of Hematology-Oncology, Pusan National University Hospital Medical Research Institute, Busan, Korea.

Correspondence to: Correspondence to Joo-Seop Chung, M.D. Department of Hematology-Oncology, School of Medicine, Pusan National University, 1-10 Ami-dong, Gudeok-ro 179, Seo-gu, Busan 602-739, Korea. Tel: +82-51-240-7225, Fax: +82-51-254-3127, Hemon@pusan.ac.kr

Received: May 12, 2014; Revised: June 13, 2014; Accepted: July 23, 2014

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Background

Although adding rituximab to the chemotherapy regimen of cyclophosphamide, vincristine, doxorubicin, and prednisone (R-CHOP) has improved clinical outcomes of patients with diffuse large B-cell lymphoma (DLBCL), several recent studies have shown that the effect of rituximab is dominantly in the non-germinal center (non-GC) subtype compared to the germinal center (GC) subtype. Natural killer (NK) cell count, a surrogate marker of immune status, is associated with clinical outcomes in DLBCL patients in the rituximab era. We investigated whether the impact of NK cells on clinical outcomes differed according to the immunophenotype of DLBCL.

Methods

This study analyzed 72 DLBCL patients treated with R-CHOP between January 2010 and January 2014.

Results

Low NK cell counts (<100/µL) were associated with poor progression-free survival (PFS) and overall survival (OS) compared to high NK cell counts. In multivariate analysis, low NK cell count was an independent prognostic factor for PFS and OS. However, survival did not significantly differ between the GC and non-GC subtypes. We examined the clinical influence of NK cells according to the immunophenotype and found that low NK cell counts were significantly associated with poor PFS and OS in non-GC cases, but not in GC cases.

Conclusion

Low NK cell counts at diagnosis are associated with poor clinical outcomes in DLBCL patients treated with R-CHOP therapy. However, the impact is significant only in non-GC subtype DLBCL, not in the GC subtype.

Keywords: Natural killer cell coun, Diffuse large B-cell lymphoma, Rituximab, Germinal center type, Non-germinal center type

Fig 1.

Figure 1.

Comparison of clinical outcomes according to immunohistochemical staining for germinal center (GC) versus non-GC subtype (A, B) or natural killer (NK) cell counts in the entire population with diffuse large B-cell lymphoma (C, D).

Blood Research 2014; 49: 162-169https://doi.org/10.5045/br.2014.49.3.162

Fig 2.

Figure 2.

Comparison of clinical outcomes according to natural killer (NK) cell counts in germinal center (GC) type (A, B) or non-GC type (C, D).

Blood Research 2014; 49: 162-169https://doi.org/10.5045/br.2014.49.3.162

Table 1 . Baseline characteristics of DLBCL patients..

Abbreviations: DLBCL, diffuse large B-cell lymphoma; ECOG, Eastern Cooperative Oncology Group; IPI, International Prognostic Index; LDH, lactate dehydrogenase; NK, natural killer..


Table 2 . Comparison of patients according to immunophenotype and NK cell count..

Abbreviations: ECOG, Eastern Cooperative Oncology Group; GC, germinal center; IPI, International Prognostic Index; LDH, lactate dehydrogenase; NK, natural killer..


Table 3 . Univariate analysis for prognostic factors in DLBCL patients..

Abbreviations: CI, confidence interval; DLBCL, diffuse large B-cell lymphoma; GC, germinal center; HR, hazard ratio; IPI, International Prognostic Index; NK, natural killer..


Table 4 . Multivariate analysis for prognostic factors in DLBCL patients..

Abbreviations: CI, confidence interval; DLBCL, diffuse large B-cell lymphoma; HR, hazard ratio; IPI, International Prognostic Index; NK, natural killer..


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