Allogeneic Hematopoietic Stem Cell Transplantation in Acute Myeloid Leukemia With Active Left Neck Tuberculosis: A Case Report

Dear Editor, A 63-year-old male was diagnosed with acute myeloid leukemia (AML-M2, AML-ETO fusion gene positive, ASXL1 mutation frequency 39%, chromosomal karyotype analysis: 45, X, -Y, t(8;21)(q22;q22), del(9)(q13q32)[19]/46, XY [1]) in June 2021 with multiple enlarged lymph nodes in the left cervical regions. Neck ultrasound showed multiple lymph node echoes were detected in the left cervical region II, III, and V. Given that the patient is a Tibetan resident with a personal history of frequent consumption of raw, unpasteurized milk and the patient's recurrent manifestations of low-grade fever, he was at risk for tuberculosis (TB) infection and the differential diagnosis for the lymphadenitis included AML and TB. Anti-TB therapy was not started with a plan to assess the lymphadenitis after the first round of chemotherapy. Following the first round chemotherapy of the IDA regimen (Idarubicin 10 mg on day 1,20 mg on days 2–3; Cytarabine 200 mg daily from day 1 to 7), a repeat ultrasound revealed that there were still several enlarged lymph nodes in zones II, III, and VB of the left neck, which were not reduced compared with those before the first chemotherapy treatment, and there was partial necrosis in zone II. A puncture biopsy of the left neck mass (Figure 1) demonstrated necrotizing granulomatous inflammation in lymphoid tissue, immunohistochemical staining was negative for CD117, CD34, MPO, and Mycobacterium tuberculosis polymerase chain reaction was positive. γ-interferon release test with reagents provided by Beijing Wantai Biopharmaceutical Company was positive. A definite diagnosis of left cervical lymph node TB was made. He was started on anti-TB therapy (isoniazid 0.3 g/day, pyrazinamide 1.0 g/day, ethambutol 1.0 g/day, and rifampicin 0.45 g/day) that had no impact on chemotherapy after a detailed consultation in the Department of Infectious Diseases and Department of Clinical Pharmacy. The second round of chemotherapy of the IDA regimen was given and the follow-up bone marrow smear and flow pattern were negative. The third round of chemotherapy of cytarabine was given to consolidate the treatment, and the repeat bone marrow showed the quantification of the AML-ETO gene in bone marrow was 0.05%. At this stage, the left cervical lesion gradually increased in size, forming a sinus tract(Figure 2A)despite 3 months of anti-TB treatment. After re-consultation with the Department of Infectious Diseases, in view of the deteriorating condition of the left cervical prior TB lesion, the original anti-TB regimen was adjusted to intensive anti-TB regimen: increasing the dose of isoniazid 0.5 g/day, pyrazinamide 1.5 g/day, and no change in the dose of ethambutol and rifampicin while the localized area was tamponaded with gauze strips containing isoniazid for drainage of secretions and local anti-infection [1]. After the fourth course of chemotherapy, the repeat bone marrow showed the patient's AML disease was in complete remission (CR). According to international guidelines [2], this patient had a high risk of relapse of AML and needed to undergo allogeneic hematopoietic stem cell transplantation(allo-HSCT) as soon as possible along with original intensive anti-TB treatment to eradicate AML and prevent disease relapse. In January 2022, we performed mixed related allo-HSCT and were given cyclosporine, mycophenolate mofetil, and a short course of methotrexate for graft-versus-host-disease (GVHD). Considering the drug interaction that rifampicin accelerates the metabolism of cyclosporine to the extent that it increases the risk of developing GVHD, the original intensive anti-TB regimen was changed from rifampicin to moxifloxacin 0.4 g/day at the beginning of transplantation preconditioning and continued during and after transplantation. Leukocyte engraftment on day +16 and platelet engraftment on day +19 of transplantation, and bone marrow smear, flow, and gene were negative after leukocyte engraftment, and peripheral blood T-cell chimerism showed complete chimerism. The prior TB lesion was gradually improved 3 months post-allo-HSCT (Figure 2B). The patient was treated with an intensive anti-TB program for 6 months after HSCT, and the total anti-TB course was 10 months [1]. At present, the patient is more than 3 years after HSCT, neither AML disease nor TB has recurred, and has returned to normal life and work status. Mycobacterium tuberculosis, an acid-fast, aerobic bacillus, stands as a major infectious disease globally [3-5]. TB is also known to be a serious opportunistic infection in HSCT recipients, with 10–40 times higher than in the general population [3, 6]. A history of previously treated active TB before transplantation and inactive TB at the time of transplantation are independent risk factors for active TB after allo-HSCT [7]. HSCT recipients exhibit immunosuppression due to underlying hematological malignancies, the requisite chemotherapy and radiation, immunosuppressive therapies, and the potential for GVHD [4]. HSCT recipients with severe immunodeficiency can develop an outbreak of pre-existing active TB infection, which ultimately leads to graft failure and may be life-threatening due to an outbreak of TB infection [8]. Therefore, it is necessary to adequately control the TB infection prior to transplantation and perform allo-HSCT after the infection has reached a stable state. However, in certain critical cases, such as AML, where CR is eventually achieved after multiple induction chemotherapy, even though active TB has not been fully controlled, urgent allo-HSCT with ongoing anti-TB therapy to prevent relapse [9]. Transplant recipients with TB are more likely to develop disseminated disease, take longer to make a definitive diagnosis, require more invasive diagnostic procedures, and experience greater toxicity associated with anti-TB treatment than the general population. Evidence suggests that transplant recipients with prior exposure to mycobacterium tuberculosis should receive treatment appropriate for latent TB infection [10, 11]. Achieving optimal management of active TB in this context is especially challenging due to the complex drug-drug interactions between anti-TB medications and immunosuppressive therapies. Fortunately, it had been reported in the literature [9] that five patients with active TB underwent transplantation on an emergency basis and all of them recovered. It further proves that specific cases in critical condition can undergo transplantation and continue to receive anti-TB treatment after transplantation. It is critical to balance the risk of progression and death without further chemotherapy and/or HSCT with the risk of progressive TB. With multi-drug therapy for TB, it may be possible to bridge the patient through the immunologic defect induced by transplant. This case supports the growing literature that patients with active TB are on active therapy and undergo urgent allo-HSCT due to the high risk of relapse of AML. Decisions to proceed should be individualized to the specifics of the patient, the susceptibility pattern of the infecting organism, and the potential drug-drug interactions that the transplant and its supportive therapies require. Yan Deng performed medical record writing, Ying He wrote the manuscript, and Hai Yi approved the version to be published. The authors thank the relatives of the patient for their consent to use his data for publication. The authors declare no conflicts of interest. None. Data supporting the results of this study are available from the corresponding author upon reasonable request.