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Bettelli, F.1; Giusti, D.1; Morselli, M.1; Paolini, A.1; Colaci, E.1; Nasillo, V.1; Messerotti, A.1; pioli, V.1; Arletti, L.1; Gilioli, A.1; Celli, M.1; Donatelli, F.1; Iotti, S.1; Catellani, H.1; Galassi, L.1; Colasante, C.1; Vallerini, D.1; Barozzi, P.1; Lagreca, I.1; Maffei, R.1; Riva, G.1; Franceschini, E.2; Codeluppi, M.2; Mussini, C.2; Marasca, R.1; Narni, F.1; Potenza, L.1; Luppi, M.1; Forghieri, F.1

doi: 10.1097/01.HS9.0000563376.59593.e6
Poster Session II: Infectious diseases

1Medical and surgical sciences

2Infectious diseases, University of Modena and Reggio Emilia, Modena, Italy

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Immunocompromised patients, especially those with hematologic malignancies or receiving hematopoietic stem cell transplant (HSCT), are susceptible to developing active tuberculosis (TB) disease with a relative risk 2-40 times higher than general population. However, scanty information is reported on prevalence and management of latent TB infection (LTBI) in patients with newly diagnosed acute leukemia or aplastic anemia (AA), especially from Western Countries

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To investigate epidemiology of LTBI in patients with acute leukemia and aplastic anemia.

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We retrospectively analyzed the prevalence of LTBI, investigated by the interferon-γ release assay (IGRA) Quantiferon®-TB (QFT) test, and the incidence of TB reactivation in 269 HIV-negative patients (median age 58 years, range 15-83) affected with either acute leukemia (AML 196, ALL 62), undergoing intensive chemotherapy or severe AA (11), under immunosuppressive regimens. Most patients (91.4%) were Caucasian, while 8.6% of subjects from our series was foreign born. Tuberculin skin test was not performed in our cohort.

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Over a period of 9 years (2010-2018), QFT results at diagnosis were available for 261 patients from our Institution. Collectively, QFT test was positive in 20 subjects (7.7%), namely 17 with AML and 3 with ALL, only 2 of them foreign born. In 34 cases (13%) QFT results were initially indeterminate due to low positive control values. However, 8 of these cases were subsequently negative on test repetition, so that the final rate of indeterminate QFT results was 9.9%. QFT test yielded positive results in 4 of 10 cases with previous TB contact. Among the 20 positive patients, LTBI was diagnosed in 19 cases, whereas a 35-year old Italian woman presented with active pulmonary TB at AML diagnosis, therefore treated with a 4-drug combination approach while receiving remission induction chemotherapy. Radiological findings consistent with LTBI, such as lung nodules or calcifications, were observed by either chest X-ray or CT scan in 7 of 19 (36.8%) positive cases. Patients with LTBI were significantly older (median age 62, range 20-78) than those with negative QFT test (median age 55, range 19-83) (p = 0.027). Treatment of LTBI with oral isoniazid (INH) 300 mg/day and concurrent pyridoxine supplementation was administered to 18 patients during intensive chemotherapy treatments, including HSCT in 6 subjects, for a median of 6 months (range 0.2-18). Conversely, one patient did not receive prophylaxis because of weak positivity of QFT test and subsequent early death secondary to septic shock during neutropenic phase. Subsequent lung infections occurred in 10 patients with LTBI, without evidence of active TB on cultural and molecular examinations. Moreover, no cases of atypical mycobacteriosis were diagnosed in QFT-positive patients. INH toxicity occurred in 6/18 cases (33.3%), namely hepatotoxicity (3), psychosis (1), skin toxicity (1) and peripheral neuropathy (in 2 patients with ALL concurrently receiving vincristine), leading to either temporary or definitive drug withdrawal in 3 and 2 patients, respectively.

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In our observational retrospective study, we documented a low prevalence of LTBI (7.3%) in newly diagnosed acute leukemia patients from an Italian center, using an IGRA as screening tool. None of these cases developed overt TB reactivation despite immunodeficiency and intensive chemotherapy. INH prophylaxis was thus feasible and active. However, prospective controlled studies are needed to further investigate efficacy and ideal duration of INH therapy for LTBI in hematologic patients.

Copyright © 2019 The Authors. Published by Wolters Kluwer Health Inc., on behalf of the European Hematology Association.