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    Reactivation of pulmonary tuberculosis in malignancy. Karnak Demet,Kayacan Oya,Beder Sumru Tumori AIMS AND BACKGROUND:Deterioration of immunity due to local or systemic effects of the tumor itself and/or administered chemotherapeutics or radiotherapy may play roles in the reactivation of tuberculosis, increasing the mortality in patients with various malignancies. In a country with a high prevalence of tuberculosis such as Turkey, most people have inactive tuberculous lesions and tuberculin test positivity. Therefore, a prospective study was carried out to investigate the frequency of tuberculosis reactivation in patients with a malignancy. METHODS:Seventy-three patients with a malignancy and undergoing diagnostic fiberoptic bronchoscopy were enrolled in the study during a 2-year period (1993-1995). Bronchoscopic biopsies and cytologic materials were obtained. Bronchoalveolar lavage fluids, bronchial washings, and pre- and postbronchoscopic sputum specimens were also evaluated for acid-fast bacilli. A diagnosis of tuberculosis was based on smear and/or culture positivity for acid-fast bacilli. RESULTS:The mean age of the patients was 56.2 +/- 13.6 years, with a male/female ratio of 69/4. The biopsy proven malignancies were as follows: primary lung carcinoma (n = 66, 90.4%), lymphoma (n = 5, 6.8%), metastatic breast adenocarcinoma (n = 1, 1.4%), and acute myelocytic leukemia (n = 1, 1.4%). Thirty-one of all patients had findings compatible with tuberculosis on radiology. The sputa and bronchial washing specimens were smear negative in all patients. Acid-fast bacilli were grown on culture in 6 patients (8%) (primary lung cancer, n = 5; non-Hodgkin lymphoma, n = 1). Four of these 6 patients had positive radiology for tuberculosis. These subjects were treated with a three- or four-drug anti-tuberculosis regimen. Two months later, smears remained acid-fast bacilli negative, or no bacilli were grown on culture. CONCLUSIONS:The possibility of coexisting tuberculosis should be kept in mind in patients with a malignancy, especially those with lung carcinoma in countries with a high prevalence of tuberculosis. Pulmonary infections encountered in such patients should raise the suspicion of tuberculosis reactivation, and in addition to direct microscopic evaluation, sputum specimens and materials obtained by fiberoptic bronchoscopy should be cultivated for tuberculosis. Three-four-drug anti-tuberculosis regimens should be given, especially in countries with high drug-resistance rates for eradicating tuberculosis.
    Utilization of whole genome sequencing for resolution of discrepant drug susceptibility results: A case report. Realegeno Susan,Adeyiga Oladunni,Winston Drew J,Beaird Omer E,Garner Omai B,Yang Shangxin IDCases A 44-year-old woman undergoing therapy for acute promyelocytic leukemia (APL) developed disseminated tuberculosis. (TB) was isolated from the blood and sputum. Initial drug susceptibility testing (DST) of the blood isolate revealed resistance to isoniazid and ethambutol but the sputum isolate showed no resistance. Due to drug resistance concerns, the patient was treated with multiple second and third-line drugs, and suffered from drug side effects. To further investigate the DST discrepancies, whole genome sequencing (WGS) was performed on both isolates. No known resistance mutations to first line or second line drugs were identified in either isolate, which was confirmed by additional susceptibility testing performed by a different reference laboratory and the California Department of Public Health (CDPH) laboratory. Treatment was reduced to a simpler and less toxic regimen due to these investigations. WGS is shown to be a valuable tool for resolving discordant phenotypic DST results of TB isolates and has the potential to provide accurate and timely results guiding appropriate therapy in the clinical setting. 10.1016/j.idcr.2021.e01308
    Localized lymphadenopathy with myelodysplastic syndrome associated with tuberculosis. Nakaya Aya,Ishii Kazuyoshi,Shimizu Toshiki,Tamaki Takeshi,Ishiura Yoshihisa,Inaba Mayumi,Uemura Yoshiko,Nakamine Hirokazu,Nomura Shosaku Hematology reports We report the case of a man who developed myelodysplastic syndrome (MDS) and refractory cytopenia of unilineage dysplasia, 5 months after aortic valve replacement surgery. He also developed fever of unknown origin. After bone marrow- and other laboratory examinations, he was diagnosed with tuberculosis. 10.4081/hr.2019.8147
    Mycobacterial Infections With Ruxolitinib: A Retrospective Pharmacovigilance Review. Anand Kartik,Burns Ethan A,Ensor Joe,Rice Lawrence,Pingali Sai Ravi Clinical lymphoma, myeloma & leukemia BACKGROUND:Ruxolitinib is a selective Janus kinase inhibitor (JAKI) 1/2 approved for the treatment of myelofibrosis (MF) and polycythemia vera (PV). These patients may be at risk for developing opportunistic infections. We assessed the number of patients that developed typical (Mycobacterium tuberculosis [MTB]) and atypical mycobacterial infections (AMI) while on treatment with ruxolitinib by utilizing the United States Food and Drug Administration (FDA) adverse events reporting system (FAERS). MATERIALS AND METHODS:This is a retrospective study utilizing FAERS, a pharmacovigilance database. We queried FAERS for cases of MTB and AMI secondary to ruxolitinib between January 1, 2011 and December 31, 2018. Disproportionality signal analysis was done by calculating the reporting odds ratio (ROR). ROR was considered significant when the lower limit of 95% confidence interval (CI) was > 1. RESULTS:There were 91 reported cases of MTB associated with ruxolitinib compared with 4575 cases from all other drugs. The ROR was significant at 9.2 (95% CI, 7.5-11.4). There were 23 reports of AMI with ruxolitinib compared with 1287 reported with all other drugs. The ROR was significant at 8.3 (95% CI, 5.5-12.6). Twelve (13.2%) patients with MTB and 8 (34.8%) with AMI died. CONCLUSION:Patients on ruxolitinib are at increased risk of developing MTB and AMI. Clinicians should be aware of this risk and consider screening patients for latent MTB prior to initiating ruxolitinib. 10.1016/j.clml.2019.08.008
    Disseminated tuberculosis in a patient treated with a JAK2 selective inhibitor: a case report. Colomba Claudia,Rubino Raffaella,Siracusa Lucia,Lalicata Francesco,Trizzino Marcello,Titone Lucina,Tolomeo Manlio BMC research notes BACKGROUND:Primary myelofibrosis is a myeloproliferative disorder characterized by bone marrow fibrosis, abnormal cytokine expression, splenomegaly and anemia. The activation of JAK2 and the increased levels of circulating proinflammatory cytokines seem to play an important role in the pathogenesis of myelofibrosis. Novel therapeutic agents targeting JAKs have been developed for the treatment of myeloproliferative disorders. Ruxolitinib (INCB018424) is the most recent among them. CASE PRESENTATION:To our knowledge, there is no evidence from clinical trials of an increased risk of tuberculosis during treatment with JAK inhibitors. Here we describe the first case of tuberculosis in a patient treated with Ruxolitinib, a male with a 12-year history of chronic idiopathic myelofibrosis admitted to our Institute because of fever, night sweats, weight loss and an enlarging mass in the left inguinal area for two months. CONCLUSION:Treatment with Ruxolitinib may have triggered the reactivation of latent tuberculosis because of an inhibition of Th1 response. Our case highlights the importance of an accurate screening for latent tuberculosis before starting an anti-JAK 2 treatment. 10.1186/1756-0500-5-552
    Disseminated tuberculosis associated with ruxolitinib. Hopman R K,Lawrence S J,Oh S T Leukemia 10.1038/leu.2014.104
    Ruxolitinib-associated tuberculosis: a case of successful ruxolitinib rechallenge. Palandri Francesca,Polverelli Nicola,Catani Lucia,Vianelli Nicola Annals of hematology 10.1007/s00277-014-2183-0
    Reactivation of Pulmonary Tuberculosis following Treatment of Myelofibrosis with Ruxolitinib. Abidi Maheen Z,Haque Javeria,Varma Parvathi,Olteanu Horatiu,Guru Murthy Guru Subramanian,Dhakal Binod,Hari Parameswaran Case reports in hematology Ruxolitinib is widely in use for treatment of myeloproliferative disorders. It causes inhibition of the Janus kinase (JAK) signal transducer and activation of transcription (STAT) pathway, which plays a key role in the underlying pathophysiology of myeloproliferative diseases. We describe a case of reactivation pulmonary tuberculosis in a retired physician while on treatment with ruxolitinib. We also review the literature on opportunistic infections following use of ruxolitinib. Our case highlights the importance of screening for latent tuberculosis in patients from highly endemic areas prior to start of therapy with ruxolitinib. 10.1155/2016/2389038
    Tuberculosis and atypical mycobacterial infections in ruxolitinib-treated patients with primary or secondary myelofibrosis or polycythemia vera. Lescuyer Sylvain,Ledoux Marie-Pierre,Gravier Simon,Natarajan-Amé Shanti,Duval Céline,Maloisel Fréderic,Mauvieux Laurent,Toussaint Elise,Fornecker Luc-Matthieu,Herbrecht Raoul International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases Ruxolitinib is a JAK-1/JAK-2 inhibitor indicated for the treatment of polycythemia vera and primary or secondary myelofibrosis. Only one patient (0.2%) was diagnosed with tuberculosis among the 485 patients receiving ruxolitinib in the four pivotal trials. Fourteen cases of tuberculosis have since been reported. We observed two (3%) mycobacterial infections (one due to Mycobacterium tuberculosis and one due to Mycobacterium avium complex) in our cohort of 65 patients receiving ruxolitinib. This observation suggests that the rate of mycobacterial infection might be higher than that observed in the pivotal trials and that atypical mycobacterial infections can also occur. 10.1016/j.ijid.2019.01.002
    A journey through infectious risk associated with ruxolitinib. Sant'Antonio Emanuela,Bonifacio Massimiliano,Breccia Massimo,Rumi Elisa British journal of haematology Ruxolitinib has proved to be effective for the treatment of patients with myelofibrosis (either primary or secondary) and polycythaemia vera, and its approval led to a significant change in the current treatment algorithm. Despite its efficacy and beyond its well described haematological toxicity, a peculiar immunosuppressive effect emerged as our clinical experience grew, both within and outside of a clinical trial setting. Definite and negative interactions with multiple pathways of the immune system of patients have been reported so far, involving both adaptive and innate immune responses. These pathophysiological mechanisms may contribute to the increased risk of reactivation of silent infections (e.g., tuberculosis, hepatitis B virus and varicella zoster virus) that have been associated with the drug. Even though such infectious events may be fatal or may lead to significant impairment of organ function, compromising the eligibility of patients for an allotransplant procedure, there are no dedicated guidelines that may help us in assessing and managing the risk of developing serious infections. On this basis, our aim for the present work was to review the current knowledge on the pathophysiological mechanisms through which ruxolitinib may exert its immunosuppressive effect, and to illustrate our personal approach to the management of three peculiar clinical scenarios, for which a risk-based algorithm is suggested. 10.1111/bjh.16174
    [Blood diseases & severe tuberculous septicemia; case report of acute leukemia with multivisceral necrosing tuberculosis]. JUSTIN-BESANCON L,PEQUIGNOT H,LOCKHART A La semaine des hopitaux : organe fonde par l'Association d'enseignement medical des hopitaux de Paris
    Disseminated tuberculosis in acute leukemia. Menon B S,Maziah W,Aiyar S,Zainul F,Shuaib I,Noh L Pediatrics international : official journal of the Japan Pediatric Society 10.1046/j.1442-200x.2001.01354.x
    Differential diagnosis between AML infiltration, lymphoma and tuberculosis in a patient presenting with fever and mediastinal lymphadenopathy: A case report. Zhao Na,Yang Jun-Jie,Zhang Guang-Sen Oncology letters The diagnosis of tuberculosis in immunocompromised hosts is often difficult as the hosts have atypical tuberculosis symptoms. The current study presents a case of scrofula and pulmonary tuberculosis with acute myelocytic leukemia (AML). As the disease became aggravated, the patient presented with fever, hemophagocytosis in the bone marrow, lymphadenopathy of the supraclavicular fossa, and mediastinal and nodular shadow in the chest by computed tomography. The symptoms presented successively or were coexistent, which made differentiation between tuberculosis, lymphoma, AML infiltration or other infections challenging. The diagnosis of tuberculosis was based on clinical and radiographic observations, morphological observation of the biopsies and the positive effect of antituberculosis drugs, while Ziehl-Neelsen stainings for acid fast bacilli were negative. The patient was treated with antituberculosis drugs, while receiving chemotherapy for AML. It is important to distinguish tuberculosis in adults with AML from other causes of fever, mediastinal masses in radiographic observations and hemophagocytosis in the bone marrow. 10.3892/ol.2014.1785
    Infections in acute myeloid leukemia: an analysis of 382 febrile episodes. Gupta Ajay,Singh Mansher,Singh Harkirat,Kumar Lalit,Sharma Atul,Bakhshi Sameer,Raina Vinod,Thulkar Sanjay Medical oncology (Northwood, London, England) Neutropenic fever is an important cause of morbidity and mortality during therapy of acute myeloid leukemia (AML). We retrospectively analyzed 382 febrile episodes encountered during induction and consolidation chemotherapy to determine the potential etiology, microbiologic spectrum, response/resistance to antibiotics and outcome. Between May, 2001 and December, 2006, 95 patients with de novo non-M3 AML received remission induction chemotherapy followed by consolidation in those who achieved complete remission. Patients median age was 28 years, ranging from 2 to 61 years, 26 patients were ≤15 years of age. There were 57 males and 38 females. Febrile neutropenia was defined as per international guidelines. A total of 382 febrile episodes were recorded; neutropenic 347 (induction phase 172, consolidation phase 175) and non-neutropenic 35 (induction 16, consolidation 19). Clinical, microbiological and radiological evidence of infection could be identified in 64% of the febrile episodes (74% during induction, 52% during consolidation). Pulmonary infections were most common, both during induction and consolidation phase. Microbiologically gram-negative infections predominated. There were 60 possible/probable/definite episodes of fungal infection. Six cases of tuberculosis (pulmonary 5 and spine 1) and 3 cases of malaria (including one case of cerebral malaria) were also identified. Nineteen patients died (17 during induction, 2 during consolidation); 17 deaths were infection related, 12/17 possibly due to fungal infections. We suggest that evaluation of antibacterial resistance patterns in an institution must be done routinely in order to choose empiric antibiotics therapy. Careful selection of antibiotics and early institution of antifungal therapy besides considering alternative diagnosis peculiar to the region (e.g. tuberculosis, malaria) may help in reducing morbidity and mortality during AML therapy. 10.1007/s12032-009-9330-9
    Cancer and tuberculosis: case series. Abul Y,Eryuksel E,Balci M,Yumuk F,Karakurt S,Ceyhan B Journal of B.U.ON. : official journal of the Balkan Union of Oncology Tuberculosis is seen with an increased frequency in cancer patients. Possible reasons of reactivation are thought to be related to chemotherapy and insufficient nutrition together with compromised immune system. The diagnosis of tuberculosis may be missed in cancer patients and may be diagnosed with newly developed radiological and clinical findings during treatment. In this case, tuberculosis should be considered and related diagnostic work up should be completed. Also, PPD test should be applied to cancer patients and if needed isoniazid prophylaxis should be initiated. We present herein 4 cancer patients diagnosed with pulmonary tuberculosis. Two patients suffered from solid malignancies (lung cancer) and 2 from non-solid malignancies (acute myeloid leukemia).
    Clinical characteristics and outcomes of Mycobacterium tuberculosis disease in adult patients with hematological malignancies. Chen Chien-Yuan,Sheng Wang-Huei,Cheng Aristine,Tsay Woei,Huang Shang-Yi,Tang Jih-Luh,Chen Yee-Chun,Wang Jaun-Yuan,Tien Hwei-Fang,Chang Shan-Chwen BMC infectious diseases BACKGROUND:Diseases caused by Mycobacterium tuberculosis (TB) among adult patients with hematological malignancies have rarely been investigated. METHODS:Adult patients with hematological malignancies at National Taiwan University Hospital between 1996 and 2009 were retrospectively reviewed. Patients with positive serology for HIV were excluded. TB disease is diagnosed by positive culture(s) in the presence of compatible symptoms and signs. The demographics, laboratory and, microbiological features, were analyzed in the context of clinical outcomes. RESULTS:Fifty-three of 2984 patients (1.78%) were diagnosed with TB disease. The estimated incidence was 120 per 100,000 adult patients with hematological malignancies. Patients with acute myeloid leukemia had a significantly higher incidence of TB disease than other subtypes of hematological malignancies (2.87% vs. 1.21%, p = 0.002, odds ratio, 2.40; 95% confidence interval, 1.39-4.41). Thirty-eight patients (72%) with non-disseminated pulmonary TB disease presented typically with mediastinal lymphadenopathy (53%), pleural effusion (47%) and fibrocalcific lesions (43%) on chest imaging. The 15 (28%) patients with extra-pulmonary disease had lower rates of defervescence within 72 h of empirical antimicrobial therapy (13% vs 45%, p = 0.03) and a higher 30-day in-hospital mortality (20% vs. 0%, p = 0.004) compared to those with disease confined to the lungs. CONCLUSIONS:TB disease is not uncommon among patients with hematological malignancies in Taiwan. Patients who received a diagnosis of extra-pulmonary TB suffered higher mortality than those with pulmonary TB alone. Clinicians should consider TB in the differential diagnoses of prolonged fever in patients with hematological malignancies, particularly in regions of high endemicity. 10.1186/1471-2334-11-324
    Tuberculosis screening: prevention in the patient with immunosuppression. McConn Kelly K,Viola George M JAAPA : official journal of the American Academy of Physician Assistants
    Mediastinal lymphadenopathy in a patient with previously treated T-cell acute lymphoblastic leukaemia. Karanth Narayan,Prabhash Kumar P,Karanth Pranjali N,Shet Tanuja,Banavali Shripad D,Parikh Purvish The Medical journal of Australia Mediastinal lymphadenopathy in a patient with previously treated T-cell acute lymphoblastic leukaemia is a diagnostic problem. The differential diagnosis in an adult is sarcoidosis, metastases, lymphoma or, rarely, tuberculosis. Mediastinal lymph node involvement is uncommon in tuberculosis. In view of its relative rarity but good prognosis, it is important to distinguish tuberculous mediastinal lymphadenitis in adults from other causes of mediastinal masses. 10.5694/j.1326-5377.2008.tb01537.x
    Acute myeloid leukemia presenting with pulmonary tuberculosis. Thomas Merlin,AlGherbawe Mushtak Case reports in infectious diseases We report the case of a 58-year-old immunocompetent man presenting with fever, cough, anorexia, weight loss, and cervical lymphadenopathy. Blood investigations revealed severe neutropenia with monocytosis. Chest imaging showed bilateral reticular infiltrates with mediastinal widening. Bronchoalveolar lavage culture and molecular test were positive for Mycobacterium tuberculosis and treatment with isoniazid, rifampicin, pyrazinamide, and ethambutol was started. Although pulmonary tuberculosis could explain this clinical presentation we suspected associated blood dyscrasias in view of significant monocytosis and mild splenomegaly. Bone marrow aspiration revealed acute myeloid leukemia. Thereafter the patient received induction chemotherapy and continued antituberculous treatment. After first induction of chemotherapy patient was in remission and successfully completed 6 months antituberculosis therapy without any complications. To our knowledge there has been no such case reported from the State of Qatar to date. 10.1155/2014/865909
    [Clinical features and toxicity of tuberculosis treatment in patients with cancer]. Cuéllar Luis,Castañeda Carlos A,Rojas Katerin,Flores Claudio,Dolores-Cerna Ketty,Castillo Miluska,Vicente William Revista peruana de medicina experimental y salud publica OBJECTIVES:To assess the clinical and epidemiological characteristics of active tuberculosis in patients with malignancy and to assess the influence of TB treatment on cancer management at the National Institute of Neoplastic Diseases from 2008 to 2013. MATERIALS AND METHODS:Observational study of TB cases diagnosed by positive sputum microscopy in patients with cancer. Clinical information, evolution, and pathologic information of neoplasia was reviewed. RESULTS:76 cases of active tuberculosis after being diagnosed with cancer were found. The median age was 51.3 years. Median follow-up was 2.1 years. The most common cancers were acute lymphocytic leukemia (14.5%), for the hematologic cancers; and cancer of the cervix (14.5%), breast (10.5%), and gastric (7.9%) for non-hematological cancers. 27.6% of patients had recurrence of the tumor; TB diagnosis confounded the initial staging by 6.9% and was initially stated as cancer recurrence in 11.1% (breast and colon cancers). The diagnosis of tuberculosis delayed or influenced the dose reduction of the antineoplastic treatment in 11.1% of the cases (acute lymphocytic leukemia and non-Hodgkin lymphoma). 8.3% of patients had toxicity to the TB treatment. CONCLUSIONS:Cancer patients may have active tuberculosis infection. The interference effect of diagnosis and treatment of tuberculosis on the assessment of cancer and cancer treatment in our series is minimal.
    Infections in patients on BCR-ABL tyrosine kinase inhibitor therapy: cases and review of the literature. Knoll Bettina M,Seiter K Infection The introduction of BCR-ABL-tyrosine kinase inhibitors (TKI) for treatment of hematologic malignancies has made a significant impact on patient outcome. Contingent upon their targeted and off-target activity, therapy-associated infectious complications may occur. We present a case of cytomegalovirus pneumonitis and a case of adenovirus hemorrhagic cystitis in two patients with Philadelphia chromosome-positive acute lymphoblastic leukemia on BCR-ABL TKI treatment and review the literature to summarize the infectious complications based on clinical data. As life-threatening infections may occur, treating physicians should maintain a heightened awareness in patients treated with BCR-ABL TKIs. Based on the frequent reports of hepatitis B virus (HBV) reactivation under the treatment BCR-ABL TKIs, screening for and prophylactic therapy of chronic HBV infection should be considered. Similarly, patients would benefit from screening for and treatment of latent tuberculosis. 10.1007/s15010-017-1105-1
    [Clinical analysis of 44 cases of leukemia complicated with active tuberculosis-a single-center report]. Li Jun,Jiang Meng,Yang Yi-ming,Liu Ting,Niu Ting Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi OBJECTIVE:To analyze the prevalence, clinical features, diagnosis, potential risk factors, anti-tuberculosis treatment efficacy and prognosis of the patients with leukemia complicated with active tuberculosis (TB). METHODS:A retrospective study was performed to analyze the clinical characteristics, relevant examination data, diagnosis methods and follow-up data about 44 leukemia cases complicated with active TB from January 2006 to December 2011 in our single center. RESULTS:The prevalence of leukemia complicated with active TB was 1.70% (pulmonary TB 1.35%, extra-pulmonary TB 0.35%) and no statistically significant difference was found between each subgroup of acute and chronic leukemia groups (P>0.05). Most of the patients were men, with a male to female ratio of 2.14:1, the median age of 40 years old (range 16 to 78), presenting as atypical clinical manifestations, such as high fever, cough, and so on. Eighteen patients (40.9%) were diagnosed with definitely etiological evidence while the other 26 patients (59.1%) were diagnosed clinically. The extra-pulmonary TB group had a higher purified protein derivative (PPD) test positive rate than that of the pulmonary TB group (88.9% vs 42.9%, P=0.020). The chest CT and T-cell spot of tuberculosis test (T-SPOT.TB) were helpful tools for diagnosis. The potential risk factors included age, sex, nutritional status, neutropenia, decreased cellular immunity, type and course of leukemia, etc. The significant differences in age, gender, administration route of immunosuppressive drugs were found between neutropenic and non-neutropenic groups (P<0.05). The efficacy of first-line anti-tuberculosis therapy was 83.7% and the total course to cure TB was around 12 months. Four patients were dead due to pulmonary TB with a 9.1% attributable mortality. CONCLUSION:The prevalence of leukemia complicated with active TB is higher than the general population in our single center. The main characteristics including various potential risk factors, atypical clinical features, diagnoses mainly made by clinical features were found in our patients with leukemia complicated with active TB. However, it showed that these patients demonstrated good responses to the first-line anti-tuberculosis therapy and relative lower attributable mortality. 10.3760/cma.j.issn.0253-2727.2013.07.003
    Endothelial lineage-specific interaction of Mycobacterium tuberculosis with the blood and lymphatic systems. Kim Paul M,Lee Jae-Jin,Choi Dongwon,Eoh Hyungjin,Hong Young-Kwon Tuberculosis (Edinburgh, Scotland) Mycobacterium tuberculosis (Mtb) has plagued humanity for tens of thousands of years, yet still remains a threat to human health. Its pathology is largely associated with pulmonary tuberculosis with symptoms including fever, hemoptysis, and chest pain. Mtb, however, also manifests in other extrapulmonary organs, such as the pleura, bones, gastrointestinal tract, central nervous system, and lymph nodes. Compared to the knowledge of pulmonary tuberculosis, extrapulmonary pathologies of Mtb are quite understudied. Lymph node tuberculosis is one of the most common extrapulmonary manifestations of tuberculosis, and presents significant challenges in its diagnosis, management, and treatment due to its elusive etiologies and pathologies. The objective of this review is to overview the current understanding of the tropism and pathogenesis of Mtb in endothelial cells of the extrapulmonary tissues, particularly, in lymph nodes. Lymphatic endothelial cells (LECs) are derived from blood vascular endothelial cells (BECs) during development, and these two types of endothelial cells demonstrate substantial molecular, cellular and genetic similarities. Therefore, systemic comparison of the differential and common responses of BECs vs. LECs to Mtb invasion could provide new insights into its pathogenesis, and may promote new investigations into this deadly disease. 10.1016/j.tube.2018.04.009
    Pulmonary tuberculosis reactivation following ruxolitinib treatment in a patient with primary myelofibrosis. Chen Yen-Hao,Lee Chen-Hsiang,Pei Sung-Nan Leukemia & lymphoma 10.3109/10428194.2014.963082
    Infectious complications in patients on treatment with Ruxolitinib: case report and review of the literature. Dioverti Maria Veronica,Abu Saleh Omar M,Tande Aaron J Infectious diseases (London, England) BACKGROUND:Primary myelofibrosis is a chronic myeloproliferative neoplasm that may cause debilitating symptoms, which can be improved with the use of Ruxolitinib, a Janus kinase 2 inhibitor. However, this agent has significant immunomodulatory effects which may increase the risk for infections. METHODS:We searched the literature and our institutional electronic medical record for reported cases of infections in adult patients on ruxolitinib treatment. RESULTS:We found 28 cases in our literature search and 4 cases from our Institution for a total of 32 cases. The most common infection was tuberculosis in 11/32 cases (34%), followed by cryptococcal infection in 3/32 (9%) and hepatitis B virus reactivation in 3/32 (9%). CONCLUSION:Opportunistic infections associated with ruxolitinib use are increasingly reported in the literature; further studies should investigate the role of systematic screening and prophylaxis against infections in this subset of patients. 10.1080/23744235.2017.1390248
    Fatal Disseminated Tuberculosis during Treatment with Ruxolitinib Plus Prednisolone in a Patient with Primary Myelofibrosis: A Case Report and Review of the Literature. Tsukamoto Yasuhiro,Kiyasu Junichi,Tsuda Mariko,Ikeda Motohiko,Shiratsuchi Motoaki,Ogawa Yoshihiro,Yufu Yuji Internal medicine (Tokyo, Japan) A 73-year-old man with primary myelofibrosis (PMF) was being treated with hydroxyurea, which was changed to ruxolitinib treatment because of worsening constitutional symptoms. Although ruxolitinib rapidly induced relief, he developed a high-grade fever. A comprehensive fever work-up found no apparent cause of the fever, except for PMF. Therefore, we increased the dose of ruxolitinib and added prednisolone, which was gradually withdrawn with resolution of the fever. However, the patient subsequently developed disseminated tuberculosis and died eight months after initiation of ruxolitinib. Our case highlights the importance of assessing and monitoring the immune status of patients receiving ruxolitinib. 10.2169/internalmedicine.9165-17
    Reactivation of tuberculosis following ruxolitinib therapy for primary myelofibrosis: Case series and literature review. Khalid Farhan,Damlaj Moussab,AlZahrani Mohsen,Abuelgasim Khadega A,Gmati Giamal Edin Hematology/oncology and stem cell therapy Primary myelofibrosis (PMF) is a subtype of BCR-ABL1 negative myeloproliferative neoplasm. Its characteristic features include clonal myeloproliferation, dysregulation of kinase signaling pathway, abnormal release of cytokines leading to fibrosis in the bone marrow, osteosclerosis, and extramedullary hematopoiesis. Approximately 20% of deaths occur because of disease progression, but death may also result occur because of cardiovascular complications or as a consequence of either infection or bleeding. The only and curative option for PMF is allogeneic hematopoietic stem cell transplant (allo-HSCT); however, the Janus kinase (JAK) 1/2 inhibitor ruxolitinib is highly effective in reducing constitutional symptoms and spleen volume, and has been found to improve survival. Ruxolitinib decreases the activity of type I T-helper cells, leading to decreased release of cytokines including tumor necrosis factor-α, interleukin-1 (IL-1), IL-6, interferon-γ, and production of IL-12, which can be a risk factor for opportunistic infections. In this report, we describe three cases of tuberculosis reactivation shortly after initiation of ruxolitinib therapy followed by a literature review. 10.1016/j.hemonc.2020.02.003
    Tuberculosis in Patients with Primary Myelofibrosis During Ruxolitinib Therapy: Case Series and Literature Review. Infection and drug resistance BACKGROUND:The selective Janus-activated kinase inhibitor ruxolitinib (rux) is now widely used to treat myelofibrosis and polycythemia vera due to its remarkable effect of reducing splenomegaly and improving constitutional symptoms. With opportunistic infections secondary to rux constantly reported; however, an increasing number of studies have begun to investigate the mechanism and underlying immunosuppressive effect of rux. CASE PRESENTATION:We report two cases of tuberculosis (TB) in primary myelofibrosis patients during rux therapy. The first patient received rux soon after diagnosis, and tracheobronchial TB (TBTB) and bronchoesophageal fistula were found after 4 months. After discontinuation of rux, antituberculosis therapy (ATT) was introduced. The second patient initiated rux due to progressive splenomegaly after 7.5 years of interferon therapy and was diagnosed with disseminated TB after 2 months. He received ATT as well. His rux was maintained due to the high burden of systematic symptoms and splenomegaly. Both myelofibrosis and TB were well controlled in these patients. CONCLUSION:This is the first case report that describes rux-related TBTB accompanied by a bronchoesophageal fistula. Through a review of the literature, we provide supporting evidence to the finding that intrinsic disorders of myeloproliferative neoplasms and rux-induced immunologic deregulation together lead to TB. We highlight the importance of screening for latent TB infection and timely chemoprophylaxis before rux therapy. Once TB is diagnosed during treatment, rux is recommended to be stopped and active ATT should begin quickly. 10.2147/IDR.S267997
    Fatal Disseminated Tuberculosis and Concurrent Disseminated Cryptococcosis in a Ruxolitinib-treated Patient with Primary Myelofibrosis: A Case Report and Literature Review. Internal medicine (Tokyo, Japan) Ruxolitinib, a Janus kinase inhibitor, improves symptoms in patients with myelofibrosis. However, its association with the development of opportunistic infections has been a concern. We herein report a 71-year-old man with primary myelofibrosis who developed disseminated tuberculosis and concurrent disseminated cryptococcosis during ruxolitinib treatment. We also reviewed the literature on disseminated tuberculosis and/or cryptococcosis associated with ruxolitinib treatment. This is the first case of disseminated tuberculosis and concurrent disseminated cryptococcosis during treatment with ruxolitinib. We therefore suggest considering not only disseminated tuberculosis but also cryptococcosis in the differential diagnosis of patients with abnormal pulmonary shadows during ruxolitinib treatment. 10.2169/internalmedicine.6436-20
    Disseminated tuberculosis with myelofibrosis presentation: a case report. Khatuni Mahdi,Ghalamkari Marziyeh,Ameli Fereshteh,Yekehtaz Habibeh Journal of medical case reports BACKGROUND:Primary myelofibrosis is a rare myeloproliferative disorder in middle-aged and old adults and should be distinguished from secondary and reactive causes of bone marrow fibrosis because, in reactive fibrosis, treatment approaches depend on the underlying etiology. CASE PRESENTATION:Here we report the case of a middle-aged Iranian man who was diagnosed and treated as primary myelofibrosis at presentation, and whose final diagnosis was disseminated tuberculosis with reactive bone marrow fibrosis. CONCLUSIONS:It is prudent to evaluate the potential causes of myelofibrosis in any patient with the diagnosis primary myelofibrosis. Tuberculosis can be an important etiology of bone marrow fibrosis, especially in endemic areas. 10.1186/s13256-021-03038-3
    The risk of tuberculosis in cancer patients is greatest in lymphoma and myelodysplastic syndrome/myeloproliferative neoplasm: a large population-based cohort study. Ganzel Chezi,Silverman Barbara,Chemtob Daniel,Ben Shoham Assaf,Wiener-Well Yonit Leukemia & lymphoma Patients with cancer are at high risk for tuberculosis (TB). This study combined the Israeli databases of cancer and TB and examined the development of TB among all newly diagnosed cancer cases from 1993 to 2013. Patients were classified into groups according to their different malignancies. Among 495,335 cancer patients, 335 developed TB following cancer diagnosis. The cumulative incidence of TB following cancer diagnosis was highest among MDS/MPN (148.8/100,000 patients) and lymphoma (154.1/100,000 patients) (p = .023). The HR of TB following cancer among hematologic patients was 2.51 (p < .001), relative to patients with in situ carcinomas/skin cancer and highest among MDS/MPN and lymphoma patients (2.74, p = .012 and 2.70, p < .001, respectively). Among lymphoma patients, a significant increased HR was found only among NHL patients (2.72, p < .001). The limitations include lack of information regarding risk factors for TB and of anti-cancer treatments. In conclusion, these data may encourage a heightened awareness for TB among patients with a background of lymphoma and MDS/MPN. 10.1080/10428194.2018.1499904
    Anti-tuberculosis agents may be associated with myelodysplastic syndromes. Wu Da-Wei,Yang Chih-Jen,Tsai Jui-Hsiu,Hsiao Hui-Hua The Kaohsiung journal of medical sciences 10.1002/kjm2.12111
    Tuberculosis in acute leukemia: a clinico-hematological profile. Mishra Pravas,Kumar Rajat,Mahapatra Manoranjan,Sharma Sanjay,Dixit Ashish,Chaterjee Tathagat,Choudhry D R,Saxena Renu,Choudhry V P Hematology (Amsterdam, Netherlands) We studied 130 consecutive cases of acute leukemia over a 2-year period and identified 9 cases (6.9%) with active tuberculosis (TB). Eight patients with TB had acute myeloid leukemia (AML). Patients with AML were more likely to develop TB as compared to patients with acute lymphoblastic leukemia (ALL) despite the wider use of steroids and radiotherapy in ALL protocols {OR 4.41 (CI 0.53-36.44)}. Only 1 patient died of disseminated TB during post induction neutropenia. All other patients were successfully managed using current anti-tuberculous therapy (ATT). On the whole, TB did not cause any undue delay in chemotherapy and did not flare up during subsequent chemotherapy cycles. However it is not a commonly described infection in acute leukemia and a high index of suspicion is warranted especially in areas endemic for TB. 10.1080/10245330600915818
    Analysis of Clinical Profile and Outcome of Tuberculosis in Patients with Acute Leukemia. Jain Arihant,Prakash Gaurav,Singh Charanpreet,Lad Deepesh,Khadwal Alka,Suri Vikas,Malhotra Pankaj,Kumari Savita,Varma Neelam,Varma Subhash Indian journal of hematology & blood transfusion : an official journal of Indian Society of Hematology and Blood Transfusion Patients with acute leukemia (AL) are predisposed to develop infections including tuberculosis (TB). The risk is specifically higher in patients from TB endemic areas. Patients (≥12 years) with AL treated between January-2014 to January-2017 who developed TB were reviewed. Patients were classified into three groups: acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML) and acute promyelocytic leukemia (APML) and a systematic analysis of clinical features and outcomes was conducted. Over the study period, 26 patients of AL developed TB. The median time to diagnosis of TB was 8 weeks (0-432 weeks) following the diagnosis of AL and it was comparable between the three leukemia groups. The diagnosis of TB required alteration of anti-leukemia therapy in 26.9% patients and rescheduling in another 42.3% patients. Therapy alteration/rescheduling were more frequent in patients with AML as compared to ALL and APML ( < 0.03, <0.04). Disseminated TB was more common in AML patients ( < 0.016). ATT could be successfully administered in 86.9% patients with improvement of TB. The incidence of ATT induced hepatitis was 34.9%. Mortality was directly attributable to TB in 10% patients. Managing tuberculosis remains a challenge during treatment of acute leukemia. With this analysis, we advocate for a need of early suspicion and evaluation for TB in patients receiving treatment for acute leukemia. Rescheduling and or alteration of anticancer therapy due to TB is associated with significantly higher mortality. Therefore, in carefully selected cases, antileukemia therapy should continue after starting ATT as early as possible. 10.1007/s12288-017-0875-z
    Successful treatment of extra-pulmonary tuberculosis presenting concomitantly with acute myeloid leukemia. Al-Tawfiq Jaffar A,Al-Khatti Adil Infection PURPOSE:There were reports of the occurrence of TB during therapy for leukemia with possible complications. In patients with acute leukemia, therapy might be delayed or complicated by the presence of tuberculosis. METHOD:We present a patient who was diagnosed with acute leukemia and concomitant tuberculosis. RESULTS:The patient's therapy of leukemia had to be delayed and he had relapse of leukemia but was subsequently treated successfully for both diseases despite a prolonged culture positivity for tuberculosis. He required a prolonged course of therapy and additional secondary anti-tuberculosis therapy. CONCLUSIONS:The possibility of tuberculosis should be considered in the differential diagnosis of patients with pneumonia, persistent fever, and those with focal signs or symptoms suggestive of tuberculosis. Despite having a sensitive organism, the infection was difficult to treat, even with the addition of two second-line drugs. The standard anti-tuberculosis therapy is usually adequate, but response may be slow, and inadequate even if the organism is sensitive requiring the addition of second-line agents. 10.1007/s15010-019-01334-1
    Epidemiology and clinical outcomes of latent tuberculosis infection in adults affected with acute leukemia or aplastic anemia: a retrospective single-center study. Bettelli Francesca,Giusti Davide,Morselli Monica,Colaci Elisabetta,Nasillo Vincenzo,Pioli Valeria,Gilioli Andrea,Iotti Silvia,Galassi Laura,Giubbolini Rachele,Colasante Corrado,Catellani Hillary,Barozzi Patrizia,Lagreca Ivana,Vallerini Daniela,Maffei Rossana,Franceschini Erica,Mussini Cristina,Banchelli Federico,D'Amico Roberto,Marasca Roberto,Narni Franco,Potenza Leonardo,Comoli Patrizia,Luppi Mario,Forghieri Fabio Annals of hematology 10.1007/s00277-020-04191-3
    Reactivation of Pulmonary Tuberculosis During Treatment of Chronic Myelomonocytic Leukemia. Pescatore Jay,Cohen Ashley,Moturi Krishna,Hernandez-Acosta Ruben Cureus A 76-year-old woman from a tuberculosis (TB) endemic region with chronic myelomonocytic leukemia (CMML) on Azacitidine presented with a non-productive cough. A CT scan of the chest revealed a lobulated opacity in the right upper lobe and antibiotic therapy was initiated for a potential bacterial pneumonia. However, a high suspicion for pulmonary TB remained given her nation of origin, immunosuppression, and imaging findings. Three sputum and bronchoalveolar lavage (BAL) acid-fast bacilli (AFB) smears with PCR testing for were negative, as were examinations for other potential fungal or bacterial etiologies of the patient's symptoms and imaging findings. While awaiting final TB culture results from BAL, her CMML underwent a transformation to acute myeloid leukemia (AML). Given the urgent need for initiation of chemotherapy, empiric treatment for TB was commenced while awaiting the final TB culture. Within 48-hours of initiating therapy for TB, the patient's fevers subsided. One week after discharge our team was notified of a positive culture from BAL. We suspect that our patient had a latent TB infection which reactivated due to her CMML. This case highlights the importance of maintaining a high clinical suspicion for TB in high-risk patients, even in the case of initially negative laboratory examinations. Further, it demonstrates the importance of screening and treating latent TB in patients with leukemias. 10.7759/cureus.15491
    Leukaemia and pulmonary tuberculosis. ABBATT J D,LEA A J Lancet (London, England) 10.1016/s0140-6736(57)92380-2
    Leukemia and tuberculosis. LOWTHER C P Annals of internal medicine 10.7326/0003-4819-51-1-52
    Tuberculosis complicating imatinib treatment for chronic myeloid leukaemia. Daniels J M A,Vonk-Noordegraaf A,Janssen J J W M,Postmus P E,van Altena R The European respiratory journal Although imatinib is not considered a predisposing factor for tuberculosis (TB), the present case report describes three patients in whom imatinib treatment for chronic myeloid leukaemia was complicated by TB. This raises the question of whether imatinib increases susceptibility to TB. There are several reports suggesting that imatinib might impair the immune system, leading to a variety of infections, including varicella zoster and hepatitis B. Control of TB in healthy individuals is achieved through acquired immunity, in which antigen-specific T-cells and macrophages arrest growth of Mycobacterium tuberculosis bacilli and maintain control over persistent bacilli. In the chronic stage of the infection, CD8+ T-cells assist macrophages in controlling intracellular mycobacteria. The T-cell receptor orchestrates this process. The fact that tyrosine kinases play an important role in T-cell receptor signal transduction and that imatinib has been shown to affect T-cell receptor signal transduction, presents a mechanism by which imatinib might impair control of Mycobacterium tuberculosis; thereby leaving the host susceptible to reactivation of tuberculosis. 10.1183/09031936.00025408
    Association of tuberculosis in patients with chronic myeloid leukemia: a treatment proposal based on literature review. Iqbal Phool,Soliman Ashraf,De Sanctis Vincenzo,Yassin Mohamed A Expert review of hematology : Chronic Myeloid leukemia (CML) is one of the first hematological malignancy linked with genetic alterations and have a targeted therapy with Tyrosine Kinase Inhibitors. However, there are certain unanswered questions and many unmet needs which limit its treatment. Concurrent Mycobacterium Tuberculosis (Mtb) infection is one of those significant factors. Tuberculosis (TB) is a highly prevalent disease in association with diabetes mellitus, malignancy, poor socioeconomic environment, HIV, and other immunosuppressive conditions in developed and developing countries. Anti-TB medications can affect other drug's pharmacokinetics by altering liver enzymes metabolism and poses treatment challenge with CML medications.: The authors performed a rigorous literature review between 2000 and 2020 using PubMed and Google Scholar, with the main focus on all articles addressing the topic of TB in CML. Authors highlighted the need to improve clinical diagnosis and to define management strategy for this dilemma.: In the current era, there are no clear guidelines or recommendations in the literature that address this problem. The aim of this review was to collect and carefully analyze the literature to highlight the need for comprehensive guidelines and propose an algorithm for better management of TB in patients with CML. 10.1080/17474086.2021.1875818