PERICARDIAL TUBERCULOSIS IN A PATIENT WITH REFRACTORY PERICARDIAL EFFUSION AND USE OF DASATINIB: CASE REPORT

• Published in: Hematology, Transfusion and Cell Therapy Vol. 46; pp. S505 - S506
• Main Authors: Oliveira, YVS, Barbosa, IR, Dezan, MFR, Lopes, LS, Farina, TR, Uliano, RL, Oliveira, LM, Palma, LC
• Format: Journal Article
• Language: English
• Published: Elsevier España, S.L.U 01.10.2024; Elsevier
• ISSN: 2531-1379
• DOI: 10.1016/j.htct.2024.09.850

Cardiovascular events have been reported in patients with chronic myeloid leukemia (CML) using tyrosine kinase inhibitors (TKIs). This study reports the occurrence of pericardial effusion (PE) refractory to usual therapy, with a final diagnosis of extrapulmonary tuberculosis (TB). By suppressing cellular immunity and compromising T lymphocyte signal transduction, TKIs are associated with tuberculosis. In vitro, dasatinib's action on Src-family kinases can impair cellular function and increase lysosomal acidification in macrophages, reducing Mycobacterium tuberculosis (Mtb) intracellular proliferation. In parallel, pleural effusion is a significant adverse effect of dasatinib. Its pathophysiology may involve increased vascular permeability via endothelial ABL kinases, Src kinases, and off-target inhibition of PDGFR-β. IgE-mediated histamine release by basophils has also been observed in vitro and may participate in dasatinib-related PE. A 45-year-old male patient was diagnosed with low-risk CML in 2019 (EUTOS, SOKAL, HASFORD). After loss of major molecular response to imatinib and grade 4 toxicity to nilotinib, he was started on dasatinib 100 mg/day. Two years and eight months later, he presented with moderate pleural and marked pericardial effusion with hemodynamic repercussions. The medication was discontinued, with pleural effusion improvement after ten days of diuretics and prednisone. Conversely, the pericardial effusion persisted. Pericardiocentesis was performed, draining 460 ml of citrine fluid. Analysis revealed glucose 126 mg/dL (serum 165 mg/dL); RBC < 10, WBC 196 cells/μL, MN 95%, PMN 3.9%; pH 7.49; Xpert MTB/RIF assay: negative. After clinical improvement and a brief reintroduction of reduced-dose dasatinib, a new severe PE occurred. Partial pleurectomy and pleuropericardial window were performed, draining 500 ml of serohematic fluid. Cytology disclosed macrophages and Xpert MTB/RIF assay trace result. The diagnosis of pericardial tuberculosis prompted the initiation of an alternative treatment with levofloxacin, isoniazid, pyrazinamide, and ethambutol due to the rifampicin-TKI interaction. Treatment resumed with bosutinib 100 mg/day, increasing to 300 mg/day, with satisfactory tolerance. A new BCR::ABL1 evaluation is in progress. Dasatinib affects Src kinases expressed by lymphocytes and macrophages, which are crucial in the response to Mycobacterium tuberculosis. The incidence of TB during TKI use varies geographically, and its incidence with dasatinib is not yet known. Nonetheless, extrapulmonary TB has been reported. The median time to development of TB after initiation of TKI treatment is not established. Dasatinib is associated with PE in 1-4% of cases. The complication usually occurs 8-12 months after treatment initiation. In severe cases, management includes dose interruption or reduction, diuretics, corticosteroids, and pericardiocentesis. Dasatinib is effective in CML, but its immunological effect requires further study. The incidence of TB varies geographically and possibly among TKIs since the dual action of dasatinib appears to interfere with cellular immunity and reduce Mtb growth in vitro. Cavitary effusions are reported at all doses of dasatinib and are generally mild and manageable, even if grade ≥3. Refractory effusions should raise suspicion of infection, especially in areas with a high prevalence of TB.