Annals of Oncology Advance Access originally published online on April 13, 2007
Annals of Oncology 2007 18(7):1243-1245; doi:10.1093/annonc/mdm107
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© 2007 European Society for Medical Oncology
supportive care |
The effect of short-term intensive chemotherapy on reactivation of tuberculosis
1 Department of Medical Oncology
2 Department of Pathology, Tata Memorial Hospital, Mumbai, Parel, Mumbai-400012, India
* Correspondence to: Dr P. Parikh, Department of Medical Oncology, Tata Memorial Hospital, Parel, Mumbai-400012, India. Tel: 22-24177213; Fax: 22-24161574; E-mail: medicaloncology{at}tatahospital.org
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Abstract |
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Background: Various malignancies and cytotoxic chemotherapy have been proposed to increase the risk of reactivation of tuberculosis. Available literature to support this observation is still conflicting. There is scarcity of data from countries with rampant tubercular infection, such as India, in this regard.
Design and methods: In the present retrospective analysis, patients with high-grade non-Hodgkin's lymphoma with past history of tuberculosis and have had adequate antitubercular therapy were identified from a Lymphoma Group study. These patients were followed up during cytotoxic chemotherapy and later to assess the risk of reactivation.
Results: A cohort of eight patients with past history of tuberculosis was selected from 141 patients of high-grade non-Hodgkin's lymphoma. The median age was 33.5 years (range, 24–53 years). Median duration between completion of antitubercular treatment and diagnosis of lymphoma was 5 years (range, 1.5–10 years). All patients received cyclical cytotoxic chemotherapy. The median duration of follow up after completion of chemotherapy was 5 years (range, 10 months to 5 years). None of these patients developed reactivation of tuberculosis.
Conclusion: Cyclical chemotherapy for non-Hodgkin's lymphoma does not lead to reactivation of tuberculosis.
Key words: cyclical chemotherapy, cytotoxic chemotherapy, lymphoma treatment, non-Hodgkin's lymphoma, reactivation, tuberculosis
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introduction |
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TopAbstractintroductionpatients and methodsresultsdiscussionconclusionsAcknowledgementsReferences |
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Since 1970, it has been recognized that cancer increases the risk for tuberculosis, especially during treatment of leukemias and Hodgkin's disease [1]. Cancer care has changed in many ways with new and more intensive treatment modalities routinely available, such as purine analogues, antilymphocyte monoclonal antibodies and hematopoietic stem-cell transplantation, which in turn influence the risk for tuberculosis. Also, improved cancer survival may have increased the number of people at risk. The current USA guidelines for the management of latent tuberculous infection indicate that foreign-born patients with underlying hematological neoplasm have a tuberculosis rate 50–100 times higher than USA-born patients, whereas USA-born patients with an underlying solid tumor had the same tuberculosis rate as USA-born persons without cancer [2].
The initial cancer types and treatment listed in 1970 which increased the risk for tuberculosis include ‘prolonged corticosteroid treatment, gastrectomy, leukemias and Hodgkin's disease’ [3]. In the early 1980s, ‘persons with head and neck cancer were added in the guidelines followed by hematological and reticulo-endothelial diseases and in year 2000 organ transplant recipients and patients receiving corticosteroid treatment’ [4, 5].
Tuberculosis continues to be a common infection in India with reported prevalence of cases in Chengulpet in Tamil Nadu as high as 10.8 per 1000 persons [6]. Among people with latent tuberculosis who have additional clinical, epidemiologic or radiographic features, the risk is considerably higher.
In the present study, we treated a group of newly diagnosed human immunodeficiency virus (HIV) seronegative adult patients with high-grade non-Hodgkin's lymphoma with a short course of chemotherapy. A cohort of patients with past history of tuberculosis was retrospectively analyzed in an attempt to assess the risk of reactivation of tuberculosis during chemotherapy treatment and follow-up.
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patients and methods |
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TopAbstractintroductionpatients and methodsresultsdiscussionconclusionsAcknowledgementsReferences |
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One forty one patients above the age of 14 years were enrolled on a Lymphoma Group study from January 1997 to January 2002. They were included in the study if they had a morphological diagnosis of high-grade non-Hodgkin's lymphoma. All patients were staged by Ann Arbor staging system and those with stage I or II disease with B symptoms and/or bulky disease (
7 cm) and stage III and IV were included in the study. Other inclusion criteria were as follows: performance status (Eastern Cooperative Oncology Group) two or less, adequate organ function (cardiac, hepatic and renal) and marrow reserve (hemoglobin 8 gm/dl, total leucocyte count 3000/cumm, absolute neutrophil count 1500/cumm and platelet count 100 14000/cumm). Patients with history of prior therapy, HIV seropositivity, and with other significant comorbidities precluding the administration of cytotoxic chemotherapy were excluded. All patients were treated with the sequential chemotherapy cycles as mentioned in Table 1 [7].
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Among this study population, a cohort with past history of tuberculosis was identified retrospectively. Those patients with definite history of tuberculosis in past and who had received adequate treatment with standard antitubercular drugs were prospectively followed up during cytotoxic chemotherapy (up to relapse/progression or the date of last visit) to assess the rate of reactivation of tuberculosis. This included thorough clinical history, examination supported with radiology (X-ray chest or computed tomography) and histopathologic examination as and when indicated.
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results |
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TopAbstractintroductionpatients and methodsresultsdiscussionconclusionsAcknowledgementsReferences |
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Among 141 patients, a cohort of eight patients was identified with past history of tuberculosis. The characteristics of these patients are given in Table 2. Seven of them have had pulmonary tuberculosis and one was having tuberculous lymphadenitis. The median age was 33.5 years (range, 24–53 years). All but one were males. All the eight patients had diffuse large B-cell non-Hodgkin's lymphoma. Four patients had stage III/IV disease whereas stage I/II with adverse factors was seen in four patients. B symptoms were present in five patients at diagnosis. Two patients had bulky disease at presentation. In response to anticancer chemotherapy, five patients were in complete remission and one was in partial remission. Two patients had progressive disease. Median duration between completion of antitubercular treatment and diagnosis of lymphoma was 5 years (range, 1.5–10 years). All patients had received four-drug antitubercular treatment for 6–9 months. The median duration of follow-up after completion of chemotherapy was 5 years (range, 10 months to 5 years). Three patients had abnormal chest X-ray (granulomas, fibrotic lesions) at the time of diagnosis of lymphoma. None of the patients developed reactivation of tuberculosis (Table 2).
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discussion |
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TopAbstractintroductionpatients and methodsresultsdiscussionconclusionsAcknowledgementsReferences |
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The menace of tuberculosis has been a global issue especially in view of ever increasing threat of HIV-AIDS. World health organization (WHO) estimates that one-third of population of world has Mycobacterium tuberculosis infection. Eight million of new cases of active tuberculosis are diagnosed annually and 2 million people die of tuberculosis each year [8]. Tuberculosis is the foremost cause of death from a single infectious agent among adults [9]. In India, scenario is even worse as indicated by WHO's 2006 report on Global Tuberculosis Control. India ranks as the World's most heavily affected country with 1.8 million new tuberculosis cases i.e. one in five of worldwide cases [10].
The primary infection by M. tuberculosis is extremely common in areas with high prevalence. It is usually self limited by the host's immune mechanisms resulting in latent infection and nonspecific or no clinical manifestations. Most cases of active tuberculosis occur due to reactivation of this latent infection in face of impaired immunity. Patients with one episode of tuberculosis are at higher risk of developing recurrent episodes due to reinfection [11].
In patients with underlying malignancies, there are three main issues as far as tuberculosis is concerned—(i) diagnostic dilemma between tuberculosis versus malignancy versus both coexisting, (ii) increase predisposition for tuberculosis due to impaired immunity (underlying malignancy and cytotoxic therapy) and (iii) atypical presentation and/or behavior of tuberculosis resulting in delayed diagnosis and poor outcome with standard antitubercular treatment.
There is scarcity of data on incidence of reactivation of tuberculosis in patients undergoing anticancer chemotherapy. The available literature is also conflicting. Certain malignancies and anticancer chemotherapy schedules are considered as risk factor for the development of tuberculosis [4]. Impairment of host defenses, poor nutrition and debility has been proposed as attributing factors for the high incidence of tuberculosis in this group. The prevalence of tuberculosis in patients with hematological malignancies has been reported to be between 0.72% and 2.6% [12]. It has the potential to be particularly high in hematological malignancies with T-cell immunodeficiency caused by the underlying disease and/or its treatment.
These observations have been negated in a study which prospectively followed 174 patients with newly diagnosed lymphoproliferative disorders >2 years. None of the patients developed reactivation of tuberculosis despite lack of antitubercular prophylaxis [13]. Our study failed to demonstrate reactivation of tuberculosis in patients having high-grade non-Hodgkin's lymphoma with past history of tuberculosis when treated with cyclical cytotoxic chemotherapy. Patients had abnormal radiographs at diagnosis of lymphoma. Abnormalities such as granuloma, healed scar are supposed to have higher bacillary load and the spread of infection has been documented to occur from the site of healed scar [14]. However, reactivation was not seen even in these patients in our study. The proposed reasons are (i) cytotoxic chemotherapy induces short lasting and cyclical immunosuppression not enough to cause the reactivation of tuberculosis, (ii) suppression of T-cell immunity may not be significant with above used chemotherapy—a major defense mechanism against M. tuberculosis.
Issues regarding atypical presentation of tuberculosis in patients with malignancies are also controversial. A study conducted in allogeneic stem-cell transplant recipients indicates that tuberculosis may have atypical extrapulmonary/disseminated presentation in this group of patients [15]. However, study by Kim et al. [14] did not support this notion and proved that malignancy has no effect on either the presentation or on the response to antitubercular treatment.
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conclusions |
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TopAbstractintroductionpatients and methodsresultsdiscussionconclusionsAcknowledgementsReferences |
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Our study documents no reactivation of tuberculosis in patients with high-grade non-Hodgkin's lymphoma undergoing cytotoxic chemotherapy. Its limitation is due to smaller number of subjects. Future studies should be planned to assess the effect of cytotoxic chemotherapy on various subsets of T cells and macrophage function in patients who have history of tuberculosis. This may help in improving our understanding of interaction between tuberculosis and underlying malignancy and its treatment.
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Acknowledgements |
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The original study was supported by grant from Indian Council of Medical Research (Government agency). This study was presented as poster in 31st European Society of Medical Oncology Congress, Istanbul, Turkey (Poster #1045P).
Received for publication December 30, 2006. Accepted for publication February 19, 2007.
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References |
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