Tuberculosis (TB) is rare following hematopoietic cell transplantation (HCT). In this multinational retrospective study, we report the frequency, characteristics, and outcome of TB following HCT performed during 2000-2019. Fifty-two patients (35 (67%) males, 15 (29%) children) from 24 centers developed TB following allogeneic (n = 47) or autologous (n = 5) HCT; with the relative frequency of 0.21% and 0.025%, respectively. Forty (77%) were bacteriologically, 12 (23%) clinically confirmed. The median time from HCT to TB was 135 (range, 16-3225) days. Eighteen (35%) patients with extrapulmonary TB (mainly involving lymph nodes and liver/spleen) were significantly younger, developed TB shorter after HCT, more often had inherited underlying disease, and received immunosuppressive therapy at TB diagnosis as compared to pulmonary TB. Five (22%) of 23 patients with drug-susceptibility testing performed, were resistant to at least one anti-TB drug. Treatment success was achieved in 38/50 (76%) of treated patients. One-year overall survival reached 75.7% and the 1-year cumulative incidence of TB-associated death was 18.1%. Concluding, TB is a rare, albeit severe complication, which can develop any time after HCT, frequently involves extrapulmonary sites, and results in high mortality rates. High proportion of drug-resistant TB warrants routine susceptibility testing.

Acibadem Saglik Hizm ve Tic A S Istanbul Turkey

Adnan Menderes University Med Faculty Aydin Turkey

Central Clinical Hospital Medical University of Warsaw Warsaw Poland

Central Hospital of Southern Pest Budapest Hungary

Centre Hospitalier Lyon Sud Lyon France

Centre National de Greffe de Moelle Tunis Tunisia

Charles University Hospital Pilsen Czech Republic

Collegium Medicum UMK University Hospital Bydgoszcz Poland

Department of Haematology Sheffield Teaching Hospitals NHS Foundation Trust Sheffield United Kingdom

Department of Hematology Poznan University of Medical Sciences Poznan Poland

EBMT Leiden Statistical Unit Leiden the Netherlands

EBMT Leiden Study Unit Leiden The Netherlands

Erasmus MC Cancer Institute Rotterdam Netherlands

Erciyes University Faculty of Medicine Kayseri Turkey

Fundeni Clinical Institute Bucharest Romania

Glasgow Royal Infirmary Glasgow United Kingdom

HELIOS Klinikum Berlin Buch Berlin Germany

Hospital Clínico Salamanca Spain

Hospital de la Princesa Madrid Spain

IRCCS Institute G Gaslini Genova Italy

IRCCS Ospedale Policlinico San Martino Genova Italy

Istanbul University Cerrahpasa Istanbul Turkey

Karolinska University Hospital Stockholm Sweden

King Abdulaziz Medical City Riyadh Saudi Arabia

King Faisal Specialist Hospital and Research Centre Riyadh Saudi Arabia

Pediatric Infectious Diseases Faculty of Medicine Hebrew University of Jerusalem; Hadassah Medical Center Jerusalem Israel

RM Gorbacheva Research Institute Pavlov University Petersburg Russian Federation

San Matteo Pavia Transplant Programme Pavia Italy

Sheffield Childrens NHS Foundation Trust Sheffield United Kingdom

University Clinical Centre in Gdansk Gdansk Poland

University Hospital | Uppsala Uppsala Sweden

University Hospital Basel Basel Switzerland

University Hospital Eppendorf Hamburg Germany

University of Genoa and IRCCS Ospedale Policlinico San Martino Genova Italy

University of Napoli Napoli Italy

Zobrazit více v PubMed

Behr MA, Kaufmann E, Duffin J, Edelstein PH, Ramakrishnan L. Latent tuberculosis: two centuries of confusion. Am J Respir Crit Care Med 2021;204:142–8. PubMed DOI PMC

Bergeron A, Mikulska M, De Greef J, Bondeelle L, Franquet T, Herrmann J-L, et al. Mycobacterial infections in adults with haematological malignancies and haematopoietic stem cell transplants: guidelines from the 8th European Conference on Infections in Leukaemia. Lancet Infect Dis. 2022;22:e359-e369.

Hyun J, Lee M, Jung I, Kim E, Hahn SM, Kim YR, et al. Changes in tuberculosis risk after transplantation in the setting of decreased community tuberculosis incidence: a national population-based study, 2008-2020. Ann Clin Microbiol Antimicrob 2024;23:1. PubMed DOI PMC

Cordonnier C, Martino R, Trabasso P, Held TK, Akan H, Ward MS, et al. Mycobacterial infection: a difficult and late diagnosis in stem cell transplant recipients. Clin Infect Dis 2004;38:1229–36. PubMed DOI

de la Cámara R, Martino R, Granados E, Rodriguez-Salvanés FJ, Rovira M, Cabrera R, et al. Tuberculosis after hematopoietic stem cell transplantation: incidence, clinical characteristics and outcome. Spanish Group on Infectious Complications in Hematopoietic Transplantation. Bone Marrow Transplant 2000;26:291–8. PubMed DOI

Lee HJ, Lee DG, Choi SM, Park SH, Cho SY, Choi JK, et al. The demanding attention of tuberculosis in allogeneic hematopoietic stem cell transplantation recipients: High incidence compared with general population. PLoS One 2017;12:e0173250. PubMed DOI PMC

Zeng QZ, Zhang YY, Wu YJ, Zhang ZY, Zhang JN, Fu HX, et al. Frequency, risk factors, and outcome of active tuberculosis following allogeneic hematopoietic stem cell transplantation. Biol Blood Marrow Transplant 2020;26:1203–9. PubMed DOI

de Oliveira Rodrigues M, de Almeida Testa LH, Dos Santos ACF, Zanetti LP, da Silva Ruiz L, de Souza MP, et al. Latent and active tuberculosis infection in allogeneic hematopoietic stem cell transplant recipients: a prospective cohort study. Bone Marrow Transplant 2021;56:2241–7. PubMed DOI

Kapoor J, Mirgh SP, Khushoo V, Mehta P, Ahmed R, Bansal N, et al. Study of clinical characteristics, risk factors and outcomes for tuberculosis post allogeneic stem cell transplant: never count it out. Ther Adv Infect Dis 2021;8:20499361211008674. PubMed PMC

Ip MS, Yuen KY, Woo PC, Luk WK, Tsang KW, Lam WK, et al. Risk factors for pulmonary tuberculosis in bone marrow transplant recipients. Am J Respir Crit Care Med 1998;158:1173–7. PubMed DOI

Yoo JW, Jo KW, Kim SH, Lee SO, Kim JJ, Park SK, et al. Incidence, characteristics, and treatment outcomes of mycobacterial diseases in transplant recipients. Transpl Int 2016;29:549–58. PubMed DOI

Roy V, Weisdorf D. Mycobacterial infections following bone marrow transplantation: a 20 year retrospective review. Bone Marrow Transplant 1997;19:467–70. PubMed DOI

Ku SC, Tang JL, Hsueh PR, Luh KT, Yu CJ, Yang PC. Pulmonary tuberculosis in allogeneic hematopoietic stem cell transplantation. Bone Marrow Transplant 2001;27:1293–7. PubMed DOI

Erdstein AA, Daas P, Bradstock KF, Robinson T, Hertzberg MS. Tuberculosis in allogeneic stem cell transplant recipients: still a problem in the 21st century. Transpl Infect Dis 2004;6:142–6. PubMed DOI

Aljurf M, Gyger M, Alrajhi A, Sahovic E, Chaudhri N, Musa M, et al. Mycobacterium tuberculosis infection in allogeneic bone marrow transplantation patients. Bone Marrow Transplant 1999;24:551–4. PubMed DOI

Agrawal N, Aggarwal M, Kapoor J, Ahmed R, Shrestha A, Kaushik M, et al. Incidence and clinical profile of tuberculosis after allogeneic stem cell transplantation. Transpl Infect Dis. 2018;20.

Lee J, Lee MH, Kim WS, Kim K, Park SH, Lee SH, et al. Tuberculosis in hematopoietic stem cell transplant recipients in Korea. Int J Hematol 2004;79:185–8. PubMed DOI

Definitions and reporting framework for tuberculosis—2013 revision (updated December 2014 and January 2020): World Health Organization; 2020 [Available from: https://apps.who.int/iris/bitstream/handle/10665/79199/?sequence=1 .

Nahid P, Dorman SE, Alipanah N, Barry PM, Brozek JL, Cattamanchi A, et al. Official American Thoracic Society/Centers for disease Control and Prevention/Infectious Diseases Society of America Clinical Practice Guidelines: treatment of drug-susceptible tuberculosis. Clin Infect Dis 2016;63:e147–e95. PubMed DOI PMC

Companion handbook to the WHO guidelines for the programmatic management of drug-resistant tuberculosis 2014 [Available from: https://apps.who.int/iris/bitstream/handle/10665/130918/9789241548809_eng.pdf .

Sun H-Y, Singh N. Opportunistic infection-associated immune reconstitution syndrome in transplant recipients. Clinical Infectious Diseases 2011;53:168–76. PubMed DOI

Global tuberculosis report 2023. Geneva: World Health Organization; 2023. Licence: CC BY-NC-SA 3.0 IGO. Geneva;2024.

Roy Chowdhury R, Vallania F, Yang Q, Lopez Angel CJ, Darboe F, Penn-Nicholson A, et al. A multi-cohort study of the immune factors associated with M. tuberculosis infection outcomes. Nature 2018;560:644–8. PubMed DOI

Elkington P, Polak ME, Reichmann MT, Leslie A. Understanding the tuberculosis granuloma: the matrix revolutions. Trends Mol Med 2022;28:143–54. PubMed DOI

Fan WC, Liu CJ, Hong YC, Feng JY, Su WJ, Chien SH, et al. Long-term risk of tuberculosis in haematopoietic stem cell transplant recipients: a 10-year nationwide study. Int J Tuberc Lung Dis 2015;19:58–64. PubMed DOI

Orfao NH, Andrade RLP, Ruffino-Netto A, da Silva LWF, Villa TCS, Seifert ML, et al. Influence of COVID-19 on the notification of drug-resistant pulmonary tuberculosis cases. BMC Infect Dis 2023;23:497. PubMed DOI PMC

8th European Conference on Infection in Leukemia. Tuberculosis (TB). 2019 [cited 2022 7 March 2022]. Available from: https://www.ebmt.org/sites/default/files/2019-12/ECIL%208-Tuberculosis%20and%20atypical%20mycobacterial%20infections%20-%20Final%20Slide%20Set.pdf .

Global Tuberculosis Report 2021. Geneva: World Health Organization; 2021. Licence: CC BY-NC-SA 3.0 IGO. Geneva;2021.

Organization WH. WHO consolidated guidelines on tuberculosis. Module 4: treatment-drug-susceptible tuberculosis treatment: World Health Organization; 2022.

Shaw ES, Stoker NG, Potter JL, Claassen H, Leslie A, Tweed CD, et al. Bedaquiline: what might the future hold? Lancet Microbe. 2024:100909.

Yamashita F, Sasa Y, Yoshida S, Hisaka A, Asai Y, Kitano H, et al. Modeling of rifampicin-induced CYP3A4 activation dynamics for the prediction of clinical drug-drug interactions from in vitro data. PLoS One 2013;8:e70330. PubMed DOI PMC

Tuloup V, France M, Garreau R, Bleyzac N, Bourguignon L, Tod M, et al. Model-based comparative analysis of rifampicin and rifabutin drug-drug interaction profile. Antimicrob Agents Chemother 2021;65:e0104321. PubMed DOI

Zelunka EJ. Intravenous cyclosporine-rifampin interaction in a pediatric bone marrow transplant recipient. Pharmacotherapy 2002;22:387–90. PubMed DOI

Almaghrabi RS, Nizami I, Alameer R, Alshehri N, Almohaizeie A, Alrajhi AA, et al. Successful use of rifamycin-sparing regimens for the treatment of active tuberculosis in lung transplant recipients. Exp Clin Transplant 2021;19:359–66. PubMed DOI

Suzuki H, Matsuda Y, Noda M, Oishi H, Watanabe T, Sado T, et al. Management of De Novo mycobacterial infection after lung transplantation without rifampicin: case series of a single institution. Transplant Proc 2018;50:2764–7. PubMed DOI

Sun HY, Munoz P, Torre-Cisneros J, Aguado JM, Lattes R, Montejo M, et al. Mycobacterium tuberculosis-associated immune reconstitution syndrome in solid-organ transplant recipients. Transplantation 2013;95:1173–81. PubMed DOI

Luetkemeyer AF, Kendall MA, Nyirenda M, Wu X, Ive P, Benson CA, et al. Tuberculosis immune reconstitution inflammatory syndrome in A5221 STRIDE: timing, severity, and implications for HIV-TB programs. J Acquir Immune Defic Syndr 2014;65:423–8. PubMed DOI