Pediatr Blood Cancer 2014;61:1484–1485
BRIEF REPORT Tuberculosis in Pediatric Oncology and Bone Marrow Transplantation Patients Andrea T. Cruz,
1,2 MD, MPH, *
Gladstone Airewele, MBBS, MPH,3 and Jeffrey R. Starke,
Five children with malignancies (3 hematologic, 1 medulloblastoma, 1 hepatoblastoma) and one bone marrow transplant patient were treated for tuberculosis over a 30-year period. Three had pulmonary disease, 3 disseminated tuberculosis, and 1 had scrofula. Four of five had positive tuberculin skin tests, cultures were positive in 5/6 children. One child died of disseminated TB after engraftment,
MD
1
and one child had hepatotoxicity likely related to tuberculosis therapy. All cases were potentially preventable had they been screened due to established risk factors of foreign birth (4/6) or parental foreign birth (2/6). All children should be screened for latent tuberculosis before chemotherapy. Pediatr Blood Cancer 2014;61: 1484–1485. # 2014 Wiley Periodicals, Inc.
Key words: latent tuberculosis infection (LTBI); Mycobacterium tuberculosis; pediatric; prevention
INTRODUCTION Prolonged fever is a common clinical scenario for pediatric oncology patients and bone marrow transplant (BMT) recipients. The evaluation has centered around fungal disease. Mycobacterium tuberculosis (TB) rarely is considered early in the evaluation process, in part due to the low-incidence of TB in the United States [1] and other industrialized nations [2]. In part due to this low-incidence, screening children for latent TB infection (LTBI) is not part of the standard evaluation for infection done before chemotherapy or conditioning for BMT. We describe six hematology-oncology patients who developed TB disease and discuss some lessons we can learn from these children.
CASES Six children with malignancy (5) or bone marrow transplantation (1) were identified from 1983 to 2013 from records of the Children’s Tuberculosis Clinic and Texas Children’s Hospital (Houston, TX) (Table I) after institutional review board approval was obtained. All presented with fever; one child also had chronic cervical adenopathy. Four of five children had positive tuberculin skin tests (TSTs); the other child was diagnosed post-mortem and a TST was not obtained. Cultures were positive in 5/6 (83%); the other child had a positive TST and a pleural punch biopsy demonstrating granulomas. Only patient #5 had been screened for latent TB infection (LTBI) prior to starting chemotherapy; he had a positive TST and was started on isoniazid. His pre-chemotherapy chest radiograph showed massive intrathoracic adenopathy and a small apical cavitary lesion thought to represent a cavitating lymphoma. While the adenopathy improved with treatment of his lymphoma, he had doubling of a pulmonary cavitary lesion by computed tomography. As he could not produce sputum, an aspirate of this lesion was performed and revealed acid-fast organisms; the culture grew M. tuberculosis. His isolate was resistant to isoniazid, but he responded well to a 9-month course of rifampin, levofloxacin, pyrazinamide, and ethambutol. Patient #3 developed hepatitis after starting multidrug TB therapy, requiring a change from standard therapy (isoniazid, rifampin, ethambutol, pyrazinamide) to a relatively liver-sparing regimen of rifampin, levofloxacin, and ethambutol. The five oncology patients received 9 months of treatment with complete resolution of their TB. Patient #6 underwent BMT for sickle cell disease and recurrent stroke. She was not screened for TB pre-BMT,
C
2014 Wiley Periodicals, Inc. DOI 10.1002/pbc.24985 Published online 20 February 2014 in Wiley Online Library (wileyonlinelibrary.com).
developed fulminant respiratory failure after engraftment, and died. Post-mortem blood and lung biopsy cultures grew M. tuberculosis.
DISCUSSION This case series demonstrates some important epidemiologic features of childhood tuberculosis and illustrates missed opportunities for prevention. There are three potential risk factors for TB in children. The first is the risk of acquisition of LTBI, which is an epidemiologic phenomenon. The second is the risk of progression to disease, which is associated with age and immune status. The third risk is disease severity; this is associated with age and immune status and may also be due to symptom duration prior to diagnosis. A recent review of U.S. pediatric TB cases found that only 25% of US children with TB lacked an international connection [3]. All patients in this series were either born abroad or had foreign-born parents. In low-incidence nations, TB often is more common in certain populations (e.g., First Nations persons in Canada [4]). Screening strategies may vary based upon local knowledge of TB epidemiology. Using standard indications for screening children for LTBI [5] alone potentially would have captured almost 70% of our patients. However, these children would have had another indication for screening: they were about to initiate chemotherapy. The most recent edition of the Red Book states that “an initial TST or interferon gamma release assay should be performed before initiation of immunosuppressive therapy, including prolonged corticosteroid administration, use of TNF-alpha antagonists, or other immunosuppressive therapy in any child requiring these treatments [6].” Despite this recommendation, many oncology patients are not routinely tested for LTBI prior to starting chemotherapy. This many stem, in part, from the perceived low risk in countries with low prevalence. Also, clinicians often do not test because they think the
1
Department of Pediatrics, Sections of Infectious Diseases, Baylor College of Medicine, Houston, Texas; 2Department of Emergency Medicine, Baylor College of Medicine, Houston, Texas; 3Department of Hematology/Oncology, Baylor College of Medicine, Houston, Texas Conflict of interest: Nothing to report. Correspondence to: Andrea T. Cruz, 6621 Fannin Street, Suite A2210, Houston, TX 77030. E-mail: [email protected]
Received 9 January 2014; Accepted 24 January 2014
TB in Pediatric Hematology-Oncology Patients
1485
TABLE I. Clinical Course for Five Children With Cancer Or Bone Marrow Transplantation and Tuberculosis Age # (years)/sex Race/ethnicity 1
2/M
Hispanic
2 3 4 5 6
5/M 10/M 10/M 18/M 18/F
Asian Hispanic Asian Asian Black
Malignancy
Site of disease
Country of birth TST (mm)
Hepatoblastoma
Disseminated (abdominal, pulmonary) ALL Pulmonary Hodgkin Lymph node Medulloblastoma Pulmonary Hodgkin Pulmonary S/p BMT for Hgb SS Disseminated (pulmonary, bacteremia)
CXR
Culture
TB outcome
US
16
Infiltrate
Positive
Survived
US Mexico Vietnam Vietnam Nigeria
18 15 0 10 ND
Pleural effusion Normal Apical nodules Cavity Infiltrates
Negative Positive Positive Positive Positive (blood and lung) at autopsy
Survived Survived Survived Survived Died
None of the children had known TB contacts, and none were known to have been screened before except for patient #5. ALL, acute lymphoblastic leukemia; BMT, bone marrow transplantation; CXR, chest radiograph; F, female; Hgb SS, hemoglobin SS disease; M, male; ND, not done; TB, tuberculosis; TST, tuberculin skin test; US, United States.
tests will be falsely negative. Both arguments have flaws. The most recent estimate of LTBI in adults in the United States was 4% [7], with estimates of 11–63% in immigrants and refugees from the five countries sending the most persons to the US (Philippines, Mexico, Burma, Vietnam, and the Dominican Republic) [8]. Approximately one-third of the global population has LTBI, and the vast majority never receive preventive therapy. Oncology patients often are screened for infections that occur at lower rates, or for infections when no therapy is available. As to the argument regarding low TST sensitivity, sensitivity is likely lower than in otherwise healthy children, so a negative test is not very helpful. However, a positive TST or an interferon gamma release assay (IGRA) provides an opportunity to treat TB LTBI, and a higher false negative rate for TSTs does not negate testing in this high-risk population. In our study, the TST was positive in 80% of children who were receiving immunosuppressive medication. While IGRAs were not available or were poorly studied in children for much of the study period, their role in augmenting the diagnosis of LTBI in oncology patients is unclear. However, in other high-risk patient populations, such as patients receiving tumor necrosis factor antagonists, some professional organizations are moving toward using both TSTs and IGRAs for LTBI testing [9]. In these patients, either test being positive would prompt evaluation for TB disease and, if disease is ruled-out, treatment for LTBI. There are multiple reports of TB in children undergoing chemotherapy or in the post-BMT period from both high- [10–12] and low-incidence [13–15] TB countries. One Indian study found that almost 2% of infections after BMT were due to M. tuberculosis [9]. Biral et al. [16] reported a case of M. tuberculosis bacteremia and pneumonia 2 months following allogeneic stem cell transplant in a Ukrainian child. The authors point out that children from high TB-incidence nations who receive BMTs in that setting have a higher rate of post-transplant BMT than children from the same settings whose BMTs occur in low TB-incidence nations. Whether this is a consequence of untreated LTBI in the donor or increased risk of exposure in the post-BMT period is unclear. An early report found higher rates of TB disease in children with hematologic malignancies and head and neck tumors compared to other common solid tumors [17]. Only one of our five oncology patients had a solid tumor outside the central nervous system (hepatoblastoma); however, this simply may reflect the epidemiology of childhood cancer. Pediatr Blood Cancer DOI 10.1002/pbc
There were limitations to this study. Given the retrospective nature, not all data elements were available for all children. Additionally, we did not have data on the total number of hematology/oncology patients cared for during the study period, precluding incidence estimates. As Houston has higher TBincidence rates than many large US cities [1], the findings may not be generalizable to other metropolitan settings. In conclusion, in this small series of six oncology or BMT patients, most children had potentially preventable disease had they been tested for LTBI prior to the initiation of chemotherapy. While TB is not a common occurrence in the pediatric oncology population in many industrialized countries, the risk of severe, sometimes fatal, disease when LTBI reactivates indicates that the benefit of testing outweighs the risk of LTBI treatment. Consideration should be given to testing children for LTBI prior to chemotherapy.
REFERENCES 1. Centers for Disease Control and Prevention. Trends in tuberculosis—United States, 2012. Morbid Mortal Wkly Rep 2013;62:201–205. 2. World Health Organization. Global tuberculosis report. 2013. Available online at: http://www.who.int/tb/ publications/global_report/en/. Accessed December 4, 2013. 3. Winston CA, Menzies HJ. Pediatric and adolescent tuberculosis in the United States, 2008-2010. Pediatrics 2012;130:e1425–e1432. 4. Smeja C, Brassard P. Tuberculosis infection in an Aboriginal (First Nations) population of Canada. Int J Tuberc Lung Dis 2000;4:925–930. 5. Centers for Disease Control and Prevention. Targeted tuberculin testing and treatment of latent tuberculosis infection. MMWR Recomm Rep 2000;49:1–51. 6. American Academy of Pediatrics. Tuberculosis. In: Pickering LK, editor. Red Book: 2012 Report of the Committee on Infectious Diseases. 29th edition. Elk Grove Village: American Academy of Pediatrics; 2012. Table 3. 76. 7. Bennett DE, Courval JM, Onorato I. et al. Prevalence of tuberculosis infection in the United States population the national health and nutrition examination survey 1999-200. Am J Respir Crit Care Med 2008;177:348–355. 8. Lee D, Philen R, Wang Z, et al. Disease surveillance among newly arriving refugees and immigrants— Electronic disease notification system, United States, 2009. Morbid Mortal Wkly Rep 2013;62:1–24. 9. Solovic I, Sester M, Gomez-Reino JJ. The risk of tuberculosis related to tumour necrosis factor antagonist therapies: A TBNET consensus statement. Eur Respir J 2010;36:1185–1206. 10. Karakas Z, Agaoglu L, Taravari B, et al. Pulmonary tuberculosis in children with Hodgkin’s lymphoma. Hematol J 2003;4:78–81. 11. George B, Mathews V, Viswabandya A, et al. Infections in children undergoing allogeneic bone marrow transplantation in India. Pediatr Transplantation 2006;10:48–54. 12. Lee JW, Kwon H-J, Jang P-S, et al. Two children with differing outcomes after treatment for pulmonary tuberculosis diagnosed after allogeneic hematopoietic stem cell transplantation. Transpl Infect Dis 2011;13:520–523. 13. Lancioni C, LaBeaud AD, Esper F, et al. Pulmonary tuberculosis presenting as fever without source in a pediatric patient with acute lymphoblastic leukemia. Pediatr Blood Cancer 2009;53:1318–1320. 14. Klossek A, Dannenberg C, Rodriguez-Feuerhahn M, et al. Pulmonary tuberculosis in a child receiving intensive chemotherapy for acute myeloblastic leukemia. J Pediatr Hematol Oncol 2004;26:64–67. 15. Vecino R, Santago B, Baquero-Artiago F, et al. Tuberculosis in pediatric solid organ and hematopoietic stem cell transplant recipients. Pediatr Infect Dis J 2012;31:774–777. 16. Biral E, Faraci M, Lanino E, et al. Mycobacterium tuberculosis pneumonia and bacteremia after allogeneic hematopoietic stem cell transplant: Report of an instructive pediatric case. New Microbiol 2012;35:353–357. 17. Kaplan M, Armstrong D, Rosen P. Tuberculosis complicating neoplastic disease: A review of 201 cases. Cancer 1974;33:850–858.
BRIEF REPORT Tuberculosis in Pediatric Oncology and Bone Marrow Transplantation Patients Andrea T. Cruz,
1,2 MD, MPH, *
Gladstone Airewele, MBBS, MPH,3 and Jeffrey R. Starke,
Five children with malignancies (3 hematologic, 1 medulloblastoma, 1 hepatoblastoma) and one bone marrow transplant patient were treated for tuberculosis over a 30-year period. Three had pulmonary disease, 3 disseminated tuberculosis, and 1 had scrofula. Four of five had positive tuberculin skin tests, cultures were positive in 5/6 children. One child died of disseminated TB after engraftment,
MD
1
and one child had hepatotoxicity likely related to tuberculosis therapy. All cases were potentially preventable had they been screened due to established risk factors of foreign birth (4/6) or parental foreign birth (2/6). All children should be screened for latent tuberculosis before chemotherapy. Pediatr Blood Cancer 2014;61: 1484–1485. # 2014 Wiley Periodicals, Inc.
Key words: latent tuberculosis infection (LTBI); Mycobacterium tuberculosis; pediatric; prevention
INTRODUCTION Prolonged fever is a common clinical scenario for pediatric oncology patients and bone marrow transplant (BMT) recipients. The evaluation has centered around fungal disease. Mycobacterium tuberculosis (TB) rarely is considered early in the evaluation process, in part due to the low-incidence of TB in the United States [1] and other industrialized nations [2]. In part due to this low-incidence, screening children for latent TB infection (LTBI) is not part of the standard evaluation for infection done before chemotherapy or conditioning for BMT. We describe six hematology-oncology patients who developed TB disease and discuss some lessons we can learn from these children.
CASES Six children with malignancy (5) or bone marrow transplantation (1) were identified from 1983 to 2013 from records of the Children’s Tuberculosis Clinic and Texas Children’s Hospital (Houston, TX) (Table I) after institutional review board approval was obtained. All presented with fever; one child also had chronic cervical adenopathy. Four of five children had positive tuberculin skin tests (TSTs); the other child was diagnosed post-mortem and a TST was not obtained. Cultures were positive in 5/6 (83%); the other child had a positive TST and a pleural punch biopsy demonstrating granulomas. Only patient #5 had been screened for latent TB infection (LTBI) prior to starting chemotherapy; he had a positive TST and was started on isoniazid. His pre-chemotherapy chest radiograph showed massive intrathoracic adenopathy and a small apical cavitary lesion thought to represent a cavitating lymphoma. While the adenopathy improved with treatment of his lymphoma, he had doubling of a pulmonary cavitary lesion by computed tomography. As he could not produce sputum, an aspirate of this lesion was performed and revealed acid-fast organisms; the culture grew M. tuberculosis. His isolate was resistant to isoniazid, but he responded well to a 9-month course of rifampin, levofloxacin, pyrazinamide, and ethambutol. Patient #3 developed hepatitis after starting multidrug TB therapy, requiring a change from standard therapy (isoniazid, rifampin, ethambutol, pyrazinamide) to a relatively liver-sparing regimen of rifampin, levofloxacin, and ethambutol. The five oncology patients received 9 months of treatment with complete resolution of their TB. Patient #6 underwent BMT for sickle cell disease and recurrent stroke. She was not screened for TB pre-BMT,
C
2014 Wiley Periodicals, Inc. DOI 10.1002/pbc.24985 Published online 20 February 2014 in Wiley Online Library (wileyonlinelibrary.com).
developed fulminant respiratory failure after engraftment, and died. Post-mortem blood and lung biopsy cultures grew M. tuberculosis.
DISCUSSION This case series demonstrates some important epidemiologic features of childhood tuberculosis and illustrates missed opportunities for prevention. There are three potential risk factors for TB in children. The first is the risk of acquisition of LTBI, which is an epidemiologic phenomenon. The second is the risk of progression to disease, which is associated with age and immune status. The third risk is disease severity; this is associated with age and immune status and may also be due to symptom duration prior to diagnosis. A recent review of U.S. pediatric TB cases found that only 25% of US children with TB lacked an international connection [3]. All patients in this series were either born abroad or had foreign-born parents. In low-incidence nations, TB often is more common in certain populations (e.g., First Nations persons in Canada [4]). Screening strategies may vary based upon local knowledge of TB epidemiology. Using standard indications for screening children for LTBI [5] alone potentially would have captured almost 70% of our patients. However, these children would have had another indication for screening: they were about to initiate chemotherapy. The most recent edition of the Red Book states that “an initial TST or interferon gamma release assay should be performed before initiation of immunosuppressive therapy, including prolonged corticosteroid administration, use of TNF-alpha antagonists, or other immunosuppressive therapy in any child requiring these treatments [6].” Despite this recommendation, many oncology patients are not routinely tested for LTBI prior to starting chemotherapy. This many stem, in part, from the perceived low risk in countries with low prevalence. Also, clinicians often do not test because they think the
1
Department of Pediatrics, Sections of Infectious Diseases, Baylor College of Medicine, Houston, Texas; 2Department of Emergency Medicine, Baylor College of Medicine, Houston, Texas; 3Department of Hematology/Oncology, Baylor College of Medicine, Houston, Texas Conflict of interest: Nothing to report. Correspondence to: Andrea T. Cruz, 6621 Fannin Street, Suite A2210, Houston, TX 77030. E-mail: [email protected]
Received 9 January 2014; Accepted 24 January 2014
TB in Pediatric Hematology-Oncology Patients
1485
TABLE I. Clinical Course for Five Children With Cancer Or Bone Marrow Transplantation and Tuberculosis Age # (years)/sex Race/ethnicity 1
2/M
Hispanic
2 3 4 5 6
5/M 10/M 10/M 18/M 18/F
Asian Hispanic Asian Asian Black
Malignancy
Site of disease
Country of birth TST (mm)
Hepatoblastoma
Disseminated (abdominal, pulmonary) ALL Pulmonary Hodgkin Lymph node Medulloblastoma Pulmonary Hodgkin Pulmonary S/p BMT for Hgb SS Disseminated (pulmonary, bacteremia)
CXR
Culture
TB outcome
US
16
Infiltrate
Positive
Survived
US Mexico Vietnam Vietnam Nigeria
18 15 0 10 ND
Pleural effusion Normal Apical nodules Cavity Infiltrates
Negative Positive Positive Positive Positive (blood and lung) at autopsy
Survived Survived Survived Survived Died
None of the children had known TB contacts, and none were known to have been screened before except for patient #5. ALL, acute lymphoblastic leukemia; BMT, bone marrow transplantation; CXR, chest radiograph; F, female; Hgb SS, hemoglobin SS disease; M, male; ND, not done; TB, tuberculosis; TST, tuberculin skin test; US, United States.
tests will be falsely negative. Both arguments have flaws. The most recent estimate of LTBI in adults in the United States was 4% [7], with estimates of 11–63% in immigrants and refugees from the five countries sending the most persons to the US (Philippines, Mexico, Burma, Vietnam, and the Dominican Republic) [8]. Approximately one-third of the global population has LTBI, and the vast majority never receive preventive therapy. Oncology patients often are screened for infections that occur at lower rates, or for infections when no therapy is available. As to the argument regarding low TST sensitivity, sensitivity is likely lower than in otherwise healthy children, so a negative test is not very helpful. However, a positive TST or an interferon gamma release assay (IGRA) provides an opportunity to treat TB LTBI, and a higher false negative rate for TSTs does not negate testing in this high-risk population. In our study, the TST was positive in 80% of children who were receiving immunosuppressive medication. While IGRAs were not available or were poorly studied in children for much of the study period, their role in augmenting the diagnosis of LTBI in oncology patients is unclear. However, in other high-risk patient populations, such as patients receiving tumor necrosis factor antagonists, some professional organizations are moving toward using both TSTs and IGRAs for LTBI testing [9]. In these patients, either test being positive would prompt evaluation for TB disease and, if disease is ruled-out, treatment for LTBI. There are multiple reports of TB in children undergoing chemotherapy or in the post-BMT period from both high- [10–12] and low-incidence [13–15] TB countries. One Indian study found that almost 2% of infections after BMT were due to M. tuberculosis [9]. Biral et al. [16] reported a case of M. tuberculosis bacteremia and pneumonia 2 months following allogeneic stem cell transplant in a Ukrainian child. The authors point out that children from high TB-incidence nations who receive BMTs in that setting have a higher rate of post-transplant BMT than children from the same settings whose BMTs occur in low TB-incidence nations. Whether this is a consequence of untreated LTBI in the donor or increased risk of exposure in the post-BMT period is unclear. An early report found higher rates of TB disease in children with hematologic malignancies and head and neck tumors compared to other common solid tumors [17]. Only one of our five oncology patients had a solid tumor outside the central nervous system (hepatoblastoma); however, this simply may reflect the epidemiology of childhood cancer. Pediatr Blood Cancer DOI 10.1002/pbc
There were limitations to this study. Given the retrospective nature, not all data elements were available for all children. Additionally, we did not have data on the total number of hematology/oncology patients cared for during the study period, precluding incidence estimates. As Houston has higher TBincidence rates than many large US cities [1], the findings may not be generalizable to other metropolitan settings. In conclusion, in this small series of six oncology or BMT patients, most children had potentially preventable disease had they been tested for LTBI prior to the initiation of chemotherapy. While TB is not a common occurrence in the pediatric oncology population in many industrialized countries, the risk of severe, sometimes fatal, disease when LTBI reactivates indicates that the benefit of testing outweighs the risk of LTBI treatment. Consideration should be given to testing children for LTBI prior to chemotherapy.
REFERENCES 1. Centers for Disease Control and Prevention. Trends in tuberculosis—United States, 2012. Morbid Mortal Wkly Rep 2013;62:201–205. 2. World Health Organization. Global tuberculosis report. 2013. Available online at: http://www.who.int/tb/ publications/global_report/en/. Accessed December 4, 2013. 3. Winston CA, Menzies HJ. Pediatric and adolescent tuberculosis in the United States, 2008-2010. Pediatrics 2012;130:e1425–e1432. 4. Smeja C, Brassard P. Tuberculosis infection in an Aboriginal (First Nations) population of Canada. Int J Tuberc Lung Dis 2000;4:925–930. 5. Centers for Disease Control and Prevention. Targeted tuberculin testing and treatment of latent tuberculosis infection. MMWR Recomm Rep 2000;49:1–51. 6. American Academy of Pediatrics. Tuberculosis. In: Pickering LK, editor. Red Book: 2012 Report of the Committee on Infectious Diseases. 29th edition. Elk Grove Village: American Academy of Pediatrics; 2012. Table 3. 76. 7. Bennett DE, Courval JM, Onorato I. et al. Prevalence of tuberculosis infection in the United States population the national health and nutrition examination survey 1999-200. Am J Respir Crit Care Med 2008;177:348–355. 8. Lee D, Philen R, Wang Z, et al. Disease surveillance among newly arriving refugees and immigrants— Electronic disease notification system, United States, 2009. Morbid Mortal Wkly Rep 2013;62:1–24. 9. Solovic I, Sester M, Gomez-Reino JJ. The risk of tuberculosis related to tumour necrosis factor antagonist therapies: A TBNET consensus statement. Eur Respir J 2010;36:1185–1206. 10. Karakas Z, Agaoglu L, Taravari B, et al. Pulmonary tuberculosis in children with Hodgkin’s lymphoma. Hematol J 2003;4:78–81. 11. George B, Mathews V, Viswabandya A, et al. Infections in children undergoing allogeneic bone marrow transplantation in India. Pediatr Transplantation 2006;10:48–54. 12. Lee JW, Kwon H-J, Jang P-S, et al. Two children with differing outcomes after treatment for pulmonary tuberculosis diagnosed after allogeneic hematopoietic stem cell transplantation. Transpl Infect Dis 2011;13:520–523. 13. Lancioni C, LaBeaud AD, Esper F, et al. Pulmonary tuberculosis presenting as fever without source in a pediatric patient with acute lymphoblastic leukemia. Pediatr Blood Cancer 2009;53:1318–1320. 14. Klossek A, Dannenberg C, Rodriguez-Feuerhahn M, et al. Pulmonary tuberculosis in a child receiving intensive chemotherapy for acute myeloblastic leukemia. J Pediatr Hematol Oncol 2004;26:64–67. 15. Vecino R, Santago B, Baquero-Artiago F, et al. Tuberculosis in pediatric solid organ and hematopoietic stem cell transplant recipients. Pediatr Infect Dis J 2012;31:774–777. 16. Biral E, Faraci M, Lanino E, et al. Mycobacterium tuberculosis pneumonia and bacteremia after allogeneic hematopoietic stem cell transplant: Report of an instructive pediatric case. New Microbiol 2012;35:353–357. 17. Kaplan M, Armstrong D, Rosen P. Tuberculosis complicating neoplastic disease: A review of 201 cases. Cancer 1974;33:850–858.
