Original Article

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Blood Res 2013; 48(1):

Published online March 31, 2013

https://doi.org/10.5045/br.2013.48.1.35

© The Korean Society of Hematology

Poor prognostic significance of Mycobacterium tuberculosis infection during bortezomib-containing chemotherapy in patients with multiple myeloma

Jae-Sook Ahn1,*, Sung Yoon Rew1,*, Deok-Hwan Yang1, Sung-Hoon Jung1, Seung-Ji Kang2, Mi-Young Kim1, Seung-Shin Lee1, Yeo-Kyeoung Kim1, Hyeoung-Joon Kim1, and Je-Jung Lee1,3*

1Department of Hematology-Oncology, Chonnam National University Hwasun Hospital, Hwasun, Korea.

2Department of Infectious Disease, Chonnam National University Hwasun Hospital, Hwasun, Korea.

3The Brain Korea 21 Project, Center for Biomedical Human Resources at Chonnam National University, Gwangju, Korea.

Correspondence to : Correspondence to Je-Jung Lee, M.D., Ph.D. Department of Hematology-Oncology, Chonnam National University Hwasun Hospital, 322, Seoyang-ro, Hwasun 519-763, Korea. The Brain Korea 21 Project, Center for Biomedical Human Resources at Chonnam National University, Gwangju, Korea. Tel: +82-61-379-7638, Fax: +82-61-379-7628, drjejung@chonnam.ac.kr

Received: August 16, 2012; Revised: January 23, 2013; Accepted: February 13, 2013

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

Bortezomib administration leads to a transient decrease in CD4+ T cells, increasing the susceptibility to opportunistic infections. The activation and proliferation of CD4+ T cells are particularly important in the host's defense against tuberculosis infection. The aim of this study was to determine the incidence and clinical significance of tuberculosis infection in patients with multiple myeloma (MM) treated with a bortezomib-containing regimen.

Methods

We retrospectively investigated the incidence of Mycobacterium tuberculosis in 115 patients with MM who were given a bortezomib-containing regimen and studied the disease prognosis.

Results

All patients received chemotherapy prior to bortezomib administration, and the median duration from diagnosis to bortezomib administration was 12.4 months (range, 0.2-230). We diagnosed tuberculosis in 8 patients (8/115, 7%): 7 patients had a pulmonary granulomatous lesion prior to chemotherapy and 1 developed reactivation of tuberculosis, but none of them died of uncontrolled tuberculosis infection. In 50% of patients with tuberculosis, bortezomib-containing therapy was interrupted. This resulted in significantly lower response rates to the bortezomib-containing therapy (P<0.05) and significantly shorter overall survival times amongst tuberculosis vs. non-tuberculosis patients (P=0.017).

Conclusion

Tuberculosis infection was not uncommon among the patients with MM who were treated with bortezomib-containing therapy, and tuberculosis infection in these patients resulted in an interruption of bortezomib administration, which significantly affected patient outcomes. Therefore, early diagnosis and treatment of tuberculosis infection are critical to avoid worsening outcomes in such patients.

Keywords Bortezomib, Mycobacterium tuberculosis, Multiple myeloma

Article

Original Article

Blood Res 2013; 48(1): 35-39

Published online March 31, 2013 https://doi.org/10.5045/br.2013.48.1.35

Copyright © The Korean Society of Hematology.

Poor prognostic significance of Mycobacterium tuberculosis infection during bortezomib-containing chemotherapy in patients with multiple myeloma

Jae-Sook Ahn1,*, Sung Yoon Rew1,*, Deok-Hwan Yang1, Sung-Hoon Jung1, Seung-Ji Kang2, Mi-Young Kim1, Seung-Shin Lee1, Yeo-Kyeoung Kim1, Hyeoung-Joon Kim1, and Je-Jung Lee1,3*

1Department of Hematology-Oncology, Chonnam National University Hwasun Hospital, Hwasun, Korea.

2Department of Infectious Disease, Chonnam National University Hwasun Hospital, Hwasun, Korea.

3The Brain Korea 21 Project, Center for Biomedical Human Resources at Chonnam National University, Gwangju, Korea.

Correspondence to: Correspondence to Je-Jung Lee, M.D., Ph.D. Department of Hematology-Oncology, Chonnam National University Hwasun Hospital, 322, Seoyang-ro, Hwasun 519-763, Korea. The Brain Korea 21 Project, Center for Biomedical Human Resources at Chonnam National University, Gwangju, Korea. Tel: +82-61-379-7638, Fax: +82-61-379-7628, drjejung@chonnam.ac.kr

Received: August 16, 2012; Revised: January 23, 2013; Accepted: February 13, 2013

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

Bortezomib administration leads to a transient decrease in CD4+ T cells, increasing the susceptibility to opportunistic infections. The activation and proliferation of CD4+ T cells are particularly important in the host's defense against tuberculosis infection. The aim of this study was to determine the incidence and clinical significance of tuberculosis infection in patients with multiple myeloma (MM) treated with a bortezomib-containing regimen.

Methods

We retrospectively investigated the incidence of Mycobacterium tuberculosis in 115 patients with MM who were given a bortezomib-containing regimen and studied the disease prognosis.

Results

All patients received chemotherapy prior to bortezomib administration, and the median duration from diagnosis to bortezomib administration was 12.4 months (range, 0.2-230). We diagnosed tuberculosis in 8 patients (8/115, 7%): 7 patients had a pulmonary granulomatous lesion prior to chemotherapy and 1 developed reactivation of tuberculosis, but none of them died of uncontrolled tuberculosis infection. In 50% of patients with tuberculosis, bortezomib-containing therapy was interrupted. This resulted in significantly lower response rates to the bortezomib-containing therapy (P<0.05) and significantly shorter overall survival times amongst tuberculosis vs. non-tuberculosis patients (P=0.017).

Conclusion

Tuberculosis infection was not uncommon among the patients with MM who were treated with bortezomib-containing therapy, and tuberculosis infection in these patients resulted in an interruption of bortezomib administration, which significantly affected patient outcomes. Therefore, early diagnosis and treatment of tuberculosis infection are critical to avoid worsening outcomes in such patients.

Keywords: Bortezomib, Mycobacterium tuberculosis, Multiple myeloma

Fig 1.

Figure 1.

Overall survival analyses in multiple myeloma patients with or without tuberculosis infection during bortezomib-containing chemotherapy (P=0.017).

Blood Research 2013; 48: 35-39https://doi.org/10.5045/br.2013.48.1.35

Table 1 . Patient characteristics and the results of bortezomib-containing chemotherapy in patients with and without tuberculosis infection..

a)P value is the comparison according to the tuberculous infection. b)P value is the comparison according to the intact immunoglobulin versus light chain disease..

Abbreviations: TB, tuberculosis; ECOG, Eastern Cooperative Oncology Group; ISS, international staging system; Vel-CD, bortezomib, cyclophosphamide, and dexamethasone; Vel-CTD, vel-CD and thalidomide; CR, complete response; VGPR, very good partial response; PR, partial response; SD, stable disease..


Table 2 . Characteristics of multiple myeloma patients diagnosed with tuberculosis infection..

Abbreviations: M, male; F, female; DSS, Durie-Salmon stage; Dx, diagnosis; ISS, international staging system; Vel, bortezomib; CTD, cyclophosphamide, thalidomide, dexamethasone; TD, thalidomide, dexamethasone; dexa, dexamethasone; VAD, vincristine, adriamycin, dexamethasone; CD, cyclophosphamide, dexamethasone; MTP, melphalan, prednisolone, thalidomide; Tx, treatment; TB, tuberculosis; VGPR, very good partial response; PR, partial response; SD, stable disease; CR, complete remission; N, no; Y, yes; CT, computed tomography; AFB, acid-fast bacillus; MM, multiple myeloma; Auto-PBSCT, autologous stem cell transplantation..


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