ACUTE LEUKEMIA AND LATENT TUBERCULOSIS INFECTION IN ITALY: QUANTIFERON-TB TEST SCREENING IN A LOW TUBERCULOSIS INCIDENCE COUNTRY

Main Article Content

Andrea Nunzi
Luigi Della Valle
Elisa Linnea Lindfors Rossi
Giorgia Ranucci
Flavia Mallegni
Federico Moretti
Elisa Meddi
Luca Guarnera
Ilaria Tiravanti
Kristian Taka
Elisa Buzzatti
Fabiana Esposito
Roberto Secchi
Francesca Di Giuliano
Flavia Chirico
Raffaele Palmieri
Luca Maurillo
Francesco Buccisano
Carmelo Gurnari
Giovangiacinto Paterno
Adriano Venditti
Maria Ilaria Del Principe

Keywords

Acute Leukemia, tubercolosis, latent tuberculosis infection, prophylaxis, Acute Myeloid Leukemia, Acute Lymphoblastic Leukemia

Abstract

Background and objectives


Identification of latent tuberculosis infection (LTBI) is a critical step of tuberculosis surveillance, especially in low incidence countries, and is limited to situations with a higher probability of developing active disease, e.g., patients with hematological malignancies. According to guidelines, in TB non-endemic countries no clear screening program is established at diagnosis for patients with acute leukemia (AL).


The primary endpoint of this study was to establish the LTBI incidence in patients with diagnosis of AL using QuantiFERON (QFT)-TB. Secondarily, TB-specific prophylaxis efficacy and safety, and features driving increased risk of LTBI were evaluated.


Methods


QFT-TB screening was performed before induction, consolidation or during follow-up, in all patients with AL (myeloid and lymphoid), treated at our Institution between October 2019 and August 2023.


Results


We accrued 62 patients, of whom 7 (11,3%) tested positive, without any symptoms or signs of active TB, and 2 (3,2%) resulted as indeterminate. All positive patients started prophylaxis with isoniazid 300 mg/die, while patients whose test was indeterminate did not receive any prophylaxis. Active TB was excluded by imaging, as well as microscopic, cultural, and molecular examination on bronchoalveolar lavage. During the 46-month period of observation, none of the patients developed TB reactivation.


Conclusions


In our country, LTBI is not uncommon as expected. Despite the low sample size, 1 out of 10 of our patients had prior TB exposure. This finding suggests implementing TB screening in the pre-treatment setting, particularly in a time when more numerous active treatments are becoming available also for patients ineligible to intensive chemotherapy.

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References

1. World Health Organization. (2023). Tuberculosis surveillance and monitoring in Europe 2023: 2021 data. Accessed October 30, 2023. Available at: https://www.ecdc.europa.eu/sites/default/files/documents/tuberculosis-surveillance-monitoring-2023.pdf
2. Getahun, H., Matteelli, A., Abubakar, I., Aziz, M. A., Baddeley, A., Barreira, D., Den Boon, S., Borroto Gutierrez, S. M., Bruchfeld, J., Burhan, E., Cavalcante, S., Cedillos, R., Chaisson, R., Chee, C. B.-E., Chesire, L., Corbett, E., Dara, M., Denholm, J., de Vries, G., ... Raviglione, M. (2015). Management of latent Mycobacterium tuberculosis infection: WHO guidelines for low tuberculosis burden countries. European Respiratory Journal, 46(6), 1563–1576. https://doi.org/10.1183/13993003.01245-2015
3. Erkens CG, Kamphorst M, Abubakar I, Bothamley GH, Chemtob D, Haas W, Migliori GB, Rieder HL, Zellweger JP, Lange C. Tuberculosis contact investigation in low prevalence countries: a European consensus. Eur Respir J. 2010;36(4):925-49. https://doi.org/10.1183/09031936.00201609
4. Compagno M, Navarra A, Campogiani L, Coppola L, Rossi B, Iannetta M, Malagnino V, Parisi SG, Mariotti B, Cerretti R, Arcese W, Goletti D, Andreoni M, Sarmati L. Latent Tuberculosis Infection in Haematopoietic Stem Cell Transplant Recipients: A Retrospective Italian Cohort Study in Tor Vergata University Hospital, Rome. Int J Environ Res Public Health. 2022;19(17):10693. https://doi.org/10.3390/ijerph191710693
5. Cheng MP, Kusztos AE, Bold TD, Ho VT, Glotzbecker BE, Hsieh C, Baker MA, Baden LR, Hammond SP, Marty FM. Risk of Latent Tuberculosis Reactivation After Hematopoietic cell Transplantation. Clin Infect Dis. 2019;69(5):869-72. https://doi.org/10.1093/cid/ciz048
6. Corradi M, Durando P, Lamberti M, Lodi V, Matteelli A, Nicosia V, Pagliaro G, Placidi D, Verso MG, Sotgiu G. (2018). Gestione e prevenzione della tubercolosi in ambito occupazionale in paesi a bassa incidenza. Giornale italiano di Medicina del Lavoro ed Ergonomia. 2018;40, 27-27.
7. Osorio-López, E. A., Vilar-Compte, D., García-Tirado, J., & Martin-Onraet, A. (2021). Prevalence of latent tuberculosis in patients with hematological neoplasms in a cancer referral hospital in Mexico City. BMC Infectious Diseases, 21(1). https://doi.org/10.1186/s12879-021-06236-y
8. Taha R, Kothari S, Foroutan F, Gitman M, Gupta V, Nguyen T, Rotstein C. Implementation of a Routine Screening Program for Latent Tuberculosis Infection among Patients with Acute Leukemia at a Canadian Cancer Center. Curr Oncol. 2022;29(12):9325-34. https://doi.org/10.3390/curroncol29120731
9. Bettelli F, Giusti D, Morselli M, Colaci E, Nasillo V, Pioli V, Gilioli A, Iotti S, Galassi L, Giubbolini R, Colasante C, Catellani H, Barozzi P, Lagreca I, Vallerini D, Maffei R, Franceschini E, Mussini C, Banchelli F, D’Amico R, Marasca R, Narni F, Potenza L, Comoli P, Luppi M, Forghieri F. Epidemiology and clinical outcomes of latent tuberculosis infection in adults affected with acute leukemia or aplastic anemia: a retrospective single-center study. Ann Hematol. 2020;99(9):2201-3. https://doi.org/10.1007/s00277-020-04191-3
10. Arber DA, Orazi A, Hasserjian R, Thiele J, Borowitz MJ, Le Beau MM, Bloomfield CD, Cazzola M, Vardiman JW. The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia. Blood. 2016;127(20):2391-405. https://doi.org/10.1182/blood-2016-03-643544
11. Döhner H, Estey E, Grimwade D, Amadori S, Appelbaum FR, Büchner T, Dombret H, Ebert BL, Fenaux P, Larson RA, Levine RL, Lo-Coco F, Naoe T, Niederwieser D, Ossenkoppele GJ, Sanz M, Sierra J, Tallman MS, Tien HF, Wei AH, Löwenberg B, Bloomfield CD. Diagnosis and management of AML in adults: 2017 ELN recommendations from an international expert panel. Blood. 2017 Jan 26;129(4):424-47. https://doi.org/10.1182/blood-2016-08-733196
12. Khoury JD, Solary E, Abla O, Akkari Y, Alaggio R, Apperley JF, Bejar R, Berti E, Busque L, Chan JK, Chen W, Chen X, Chng WJ, Choi JK, Colmenero I, Coupland SE, Cross NC, De Jong D, Elghetany MT, Takahashi E, Emile JF, Ferry J, Fogelstrand L, Fontenay M, Germing U, Gujral S, Haferlach T, Harrison C, Hodge JC, Hu S, Jansen JH, Kanagal-Shamanna R, Kantarjian HM, Kratz CP, Li XQ, Lim MS, Loeb K, Loghavi S, Marcogliese A, Meshinchi S, Michaels P, Naresh KN, Natkunam Y, Nejati R, Ott G, Padron E, Patel KP, Patkar N, Picarsic J, Hochhaus A. The 5th edition of the World Health Organization Classification of Haematolymphoid Tumours: Myeloid and Histiocytic/Dendritic Neoplasms. Leukemia https://doi.org/10.1038/s41375-022-01613-1
13. Döhner H, Wei AH, Appelbaum FR, Craddock C, DiNardo CD, Dombret H, Ebert BL, Fenaux P, Godley LA, Hasserjian RP, Larson RA, Levine RL, Miyazaki Y, Niederwieser D, Ossenkoppele GJ, Röllig C, Sierra J, Stein EM, Tallman MS, Tien HF, Wang J, Wierzbowska A, Löwenberg B. Diagnosis and Management of AML in Adults: 2022 ELN Recommendations from an International Expert Panel. Blood. 2022. https://doi.org/10.1182/blood.2022016867
14. Charlson ME, Pompei P, Ales KL, MacKenzie CR. A new method of classifying prognostic comorbidity in longitudinal studies: Development and validation. J Chronic Dis. Jan 1987;40(5):373-83. https://doi.org/10.1016/0021-9681(87)90171-8
15. Anibarro L, Pena A. Tuberculosis in patients with hematological malignancies. Mediterr J Hematol Infect Dis. 2014;6(1). https://doi.org/10.4084/mjhid.2014.026
16. Al-Anazi, K., Al-Jasser, A., & Evans, D. (2007). Infections caused by mycobacterium tuberculosis in patients with hematological disorders and in recipients of hematopoietic stem cell transplant, a twelve-year retrospective study. Annals of Clinical Microbiology and Antimicrobials, 6(1), 16. https://doi.org/10.1186/1476-0711-6-16
17. Parrish, N. M., Dick, J. D., & Bishai, W. R. (1998). Mechanisms of latency in Mycobacterium tuberculosis. Trends in Microbiology, 6(3), 107–112. https://doi.org/10.1016/s0966-842x(98)01216-5
18. Hernández-Pando, R., Jeyanathan, M., Mengistu, G., Aguilar, D., Orozco, H., Harboe, M., Rook, G., & Bjune, G. (2000). Persistence of DNA from Mycobacterium tuberculosis in superficially normal lung tissue during latent infection. The Lancet, 356(9248), 2133–2138. https://doi.org/10.1016/s0140-6736(00)03493-0
19. Arriaga, A. K., Orozco, E. H., Aguilar, L. D., Rook, G. A. W., & Pando, R. H. (2002). Immunological and pathological comparative analysis between experimental latent tuberculous infection and progressive pulmonary tuberculosis. Clinical & Experimental Immunology, 128(2), 229–237. https://doi.org/10.1046/j.1365-2249.2002.01832.x
20. Barrios-Payán, J., Saqui-Salces, M., Jeyanathan, M., Alcántara-Vazquez, A., Castañon-Arreola, M., Rook, G., & Hernandez-Pando, R. (2012). Extrapulmonary Locations of Mycobacterium tuberculosis DNA During Latent Infection. The Journal of Infectious Diseases, 206(8), 1194–1205. https://doi.org/10.1093/infdis/jis381
21. Narasimhan, P., Wood, J., MacIntyre, C. R., & Mathai, D. (2013). Risk Factors for Tuberculosis. Pulmonary Medicine, 2013, 1–11. https://doi.org/10.1155/2013/828939
22. Pai, M., Denkinger, C. M., Kik, S. V., Rangaka, M. X., Zwerling, A., Oxlade, O., Metcalfe, J. Z., Cattamanchi, A., Dowdy, D. W., Dheda, K., & Banaei, N. (2014). Gamma Interferon Release Assays for Detection of Mycobacterium tuberculosis Infection. Clinical Microbiology Reviews, 27(1), 3–20. https://doi.org/10.1128/cmr.00034-13
23. Deuffic-Burban, S., Atsou, K., Viget, N., Melliez, H., Bouvet, E., & Yazdanpanah, Y. (2010). Cost-effectiveness of QuantiFERON®-TB test vs. tuberculin skin test in the diagnosis of latent tuberculosis infection. The International journal of tuberculosis and lung disease, 14(4), 471-481.
24. Huang, C.-C., Jerry Teng, C.-L., Wu, M.-F., Lee, C.-H., Chen, H.-C., & Huang, W.-C. (2021). Features of indeterminate results of QuantiFERON-TB Gold In-Tube test in patients with haematological malignancies. Therapeutic Advances in Hematology, 12, 204062072110284. https://doi.org/10.1177/20406207211028437
25. Sánchez-García, E. M., Gamallo, R., Blanco-Moure, A., Viejo, M. A., Amador, L., & Anibarro, L. (2013). Toxicity and adherence to treatment for latent tuberculosis infection in patients with hematologic malignancies. Infection, 41(5), 903–907. https://doi.org/10.1007/s15010-013-0489-9