A 58-year-old man was admitted to a local hospital in March 2022 due to nausea and vomiting. His blood test results showed that he had a white blood cell count (WBC) of 25.3 x 109/L, hemoglobin (HB) 65 g/L, and platelet (PLT) 190 x 109/L. At the time, the doctor considered the possibility of acute leukemia. He was then transferred to the Hematology Department of The First Affiliated Hospital, Zhejiang University School of Medicine. When the patient's bone marrow was examined, the findings revealed that there was clearly active mononuclear system hyperplasia, with 51% of original mononuclear cells and immature mononuclear cells. Bone marrow flow cytometry indicated that the original myeloid cell population accounted for 20.46% of non-erythroid cells, expressing CD117, CD34, CD33, CD13, HLA-DR, CD38, CD123, and CD56. The chromosome was a normal karyotype. BCR/ABL, AML1/ETO, and PML/RaRalphafusion genes were all negative. DNMT3A (mutation rate 48.02%), FLT3-TKD (mutation rate 36.3%), and IDH2 (mutation rate 45.95%) were found by next-generation sequencing (NGS). The patient was diagnosed as having acute myeloid leukemia (AML)-M5b with DNMT3A, FLT3-TKD, and IDH2 mutations. Following the admission, the patient's general condition was assessed and symptomatic supportive care was intensified. But chest computed tomography (CT) revealed two pulmonary tuberculosis (TB). In the sputum, acid-fast bacillus (AFB) 3+ was found. The patient received 2 months of TB pleurisy treatment 30 years ago and then stopped taking tuberculous drugs.
On March 23, the patient was transferred to the TB Department of our hospital. Blood counts were WBC 29.9 x 109/L, neutrophils 17.9 x 109/L, HB 60 g/L, PLT 175 x 109/L, with manual classification showing abnormal cells in 15%. Two pulmonary TB lesions were visible on a chest CT, and the right upper lung cavity had formed (Figures 1A1, A2). The patient immediately received HRZE (Isohydrazide 0.3 g QD + Rifampicin 0.45 g QD + Pyrazinamide 1.5 g QD + Ethambutol 0.75 g QD) regimen anti-TB therapy. The patient's WBC did, nevertheless, reach a maximum of 99 x 109/L, and neutrophils reached 59.8 x 109/L. He was treated with hydroxycarbamide for the purpose of reducing his WBC count. When sputum smears were negative for 3 consecutive times, blood counts were WBC 11.9 x 109/L, neutrophils 7.8 x 109/L, HB 52 g/L, and PLT 74 x 109/L.
On April 8, he was transferred to the Hematology Department of our hospital and started receiving VA (Venetoclax 100 mgd1, 200 mg d2-7+Azacytidine 100 mgd1-7) regimen anti-leukemia therapy immediately. Due to venetoclax and rifampicin conflict, the regimen of anti- TB regimen was adjusted to Levofloxacin 0.5 g QD + Isohydrazide 0.45 g QD + Pyrazinamide 1.5 g QD + Ethambutol 0.75 g QD. Following one course of the VA regimen, the bone marrow routine showed 4% primitive mononuclear cells and 35% naive mononuclear cells. A total 28% of juvenile mononuclear cells were identified by bone marrow flow cytometry. The chromosome was a normal karyotype. NGS highlighted DNMT3A (mutation rate 45.6%), FLT3-TKD (mutation rate 26.7%) and IDH2 (mutation rate 32.9%). On May 6, the patient was given HVA (Homoharringtonine 2 mg d1-7 + Venetoclax 100 mg d1, 200 mg d2-7 + Azacytidine 100 mg d1-7) regimen anti-leukemia therapy. On May 25, the blood counts routine showed WBC 5.2 x 109/L, neutrophils 4.7 x 109/L, HB 64 g/L, and PLT 336 x 109/L. The original mononuclear cells in the bone marrow routine were only 1%. Flow cytometry of bone marrow showed no blasts with obvious immunophenotypic abnormalities. NGS test exhibited DNMT3A (mutation rate 44.7%), and no mutation was detected in IDH2 and FLT3-TKD. After that, the patient underwent three cycles of the HVA regimen anti-leukemia therapy consecutively on June 1, July 8, and August 9, and no abnormalities were found in multiple bone marrow routines and flow cytometry. On August 23, NGS showed DNMT3A (mutation rate 46.5%), with no mutation detected in IDH2 and FLT3-TKD. Moreover, on July 5, and on August 3, respectively reviews of chest CT suggested the lung TB foci progressive reduction (Figures 1B1, B2, C1, C2). No AFB was repeatedly detected in the sputum. He was treated with intrathecal chemotherapy three times (cytarabine 50 mg + methotrexate 15 mg + dexamethasone 5 mg) for the purpose of preventing the growth of central leukemia. On September 15, the blood routine showed WBC 4.1 x 109/L, neutrophils 2.63 x 109/L, HB 121 g/L, and PLT 242 x 109/L. The patient has now had a bone marrow transplant. The adverse reactions of the patient during the use of HVA regimen are shown in Table 1.