Anti‐tuberculosis agents may be associated with myelodysplastic syndromes

Therapy-related myelodysplastic syndrome (t-MDS) always occurs as a late complication of cytotoxic chemotherapy and/or radiation therapy administered for a prior neoplastic or non-neoplastic disorder. Noncytotoxic drug-related MDS is extremely rare in t-MDS. Herein, we present a case of a tuberculosis patient who had possible t-MDS after receiving antituberculosis (anti-TB) agents for 3 months. A 65-year-old male without systemic diseases presented with fever, cough with scanty sputum, and weight loss of 5 kg within 1 month. He visited our hospital on August 3, 2016, and chest X-ray revealed bilateral effusion (Figure 1A). His blood test revealed a normal white blood cell (WBC) count, 4.09 × 1000/μL, and absence of blast cells in peripheral blood. Pleural effusion acid-fast staining and TB polymerase chain reaction revealed positive results for TB. Both pleural effusion and sputum TB cultures confirmed TB infection, which had low-grade resistance to isoniazid. Therefore, a standard anti-TB treatment in combination with rifampin, isoniazid, ethambutol, and pyrazinamide was soon administered once daily. He received anti-TB drugs until day 97, which were then stopped due to severe pancytopenia (WBC count 1.56 × 1000/μL, platelet count 40 × 1000/μL, and hemoglobin 9.6 g/dL) with young cells. Bone marrow biopsy revealed MDS-refractory anemia with excess blast-2 (Figure 1B-D) with blast cells around 20%, and cytogenetic analysis revealed a normal karyotype of 46,XY, indicating the possibility of secondary MDS; in other words, it may be t-MDS. First-line chemotherapy was initiated from January 19, 2017, consisting of a 7-day course of 100 mg azacitidine administered subcutaneously every month until July 2017. His MDS also gradually stabilized after chemotherapy treatment. Meanwhile, we restarted anti-TB treatment course from March 3, 2017, comprising rifampin, pyrazinamide, and ethambutol every day until day 183. Neither pleural effusion nor further evidence of TB was detected later. This may be the first case report of anti-TB therapy-related MDS in Taiwan. t-MDS has been reported after treatment for various hematologic and solid malignancies; both radiation and cytotoxic chemotherapy have been associated with t-MDS.1 About 10% to 20% of cases of therapy-related myeloid neoplasm/MDS occur in patients treated receiving radiotherapy or chemotherapy.2 Patients with stomach, colorectal, liver, breast, endometrial, prostate, and kidney cancers who receive therapeutic radiation therapy seem to be at a significantly higher risk of developing t-MDS, and patients treated with chemotherapy for their primary malignancy have an increased risk of t-MDS.1 Approximately 16.6% of patients who received first-line anti-TB drugs developed leukopenia after 8 weeks.3 t-MDS has been reported in patients who received rifampicin.4 Recently, a case-control study showed that previous anti-TB drug administration was an independent risk factor for MDS.5 In addition, though chromosomal abnormalities are seen in 80% to 90% of cytotoxic- and radiotherapy-related MDS cases,1 no chromosomal abnormality was detected in this case; maybe the anti-TB agents were not cytotoxic. Since Taiwan is an endemic area of TB infection, adverse drug reactions and/or side effects of anti-TB agents are important. In this report, we highlight the possibility of occurrence of t-MDS with anti-TB therapy.