Pulmonary tuberculosis in a case of acute myeloid leukemia during consolidation chemotherapy

Abstract

Tuberculosis in acute myeloid leukemia (AML) has rarely been reported. Herein, we report the diagnosis and treatment of a patient with AML who was finally diagnosed with pulmonary tuberculosis following consolidation chemotherapy. In this case, chest CT showed space-occupying lesions near the right pulmonary hilum after the second cycle of consolidation chemotherapy. Initially, extramedullary infiltration of AML and lung cancer were considered. After consolidation chemotherapy, antibiotics were simultaneously administered, but persistent fever continued. Later, based on the positive acid-fast staining of the tissue puncture following tracheoscopy and the sputum, the patient was diagnosed to have pulmonary tuberculosis and immediately transferred to a dedicated tuberculosis hospital for anti-tuberculosis treatment. Unfortunately, the patient died of respiratory failure 3 months later. In conclusion, in cases wherein AML patients have persistent fever or pulmonary space-occupying lesions of unknown causes during chemotherapy, the possibility of tuberculosis should be considered. Early diagnosis and targeted anti-tuberculosis treatment may significantly improve the prognosis of patients.

Introduction

In recent years, the incidence of active pulmonary tuberculosis has gradually declined; however, patients with hematological malignancies are more prone to infections due to the disease itself, repeated intensive chemotherapy, and other reasons, sometimes even infection or resurgence of tuberculosis. Although the incidence rate of tuberculosis is high in the general population, tubercular re-activation is seldom suspected in patients with acute leukemia, and lesions found on imaging are usually considered as fungal causes. ¹ Following onset of tuberculosis, the routine chemotherapy of AML patients may need to be interfered, and if undiagnosed and untreated in time, the infection can be fatal. However, because the clinical manifestations of pulmonary tuberculosis are often atypical and leukemia itself may interfere with the interpretation of the routine diagnosis and limit specific examinations such as lung puncture, the clinical diagnosis is difficult. Therefore, it is particularly important to identify suspected tuberculosis patients and arrive at a definitive diagnosis.

Herein, we report the diagnosis and treatment of a patient with AML who was finally diagnosed with pulmonary tuberculosis after receiving consolidation chemotherapy.

Case description

A 64 year-old male presented with fatigue and general unwellness 15 days before. The initial laboratory data were as follows: WBC count 6.26 × 10⁹/L, neutrophil 4.05 ×10⁹/L, hemoglobin 3.9 g/dL, and platelet count 7 × 10⁹/L. Morphological and flow cytometric analysis of the bone marrow cells revealed AML. The analysis of bone marrow chromosome showed 45, X, -Y, der (8) t (8; 21) (q22; q22), add (11) (p15), der (21). Bone marrow showed positivity for the fusion genes RUNX1/RUNX1T1. The AML-FISH panel did not reveal any other abnormalities. Based on the clinical and laboratory findings (M2, RUNX1/RUNX1T1 positivity with complex chromosome karyotype), AML was diagnosed. The previous medical history of the patient was unremarkable.

After diagnosis, the patient was treated with a standard AML induction regimen with decitabine 25 mg/m² on days 1–3, homoharringtonine 2 mg/m² on days 4–7, cytarabine 15 mg/m² twice a day on days 1–14, and recombinant human granulocyte colony stimulating factor 300 μg injection on days 1–14. However, the bone marrow results show no remission. Next, the patient received a re-induction regimen comprising decitabine 25 mg/m² on days 1–3, daunorubicin 60 mg/m² on days 1–3, and cytarabine 100 mg/m² on days 1–7, and achieved complete remission. Later, the patient received two cycles of chemotherapy of this regimen as consolidation chemotherapy. The patient developed severe pulmonary infection after the last two chemotherapy sessions, and no space-occupying lesions were seen on multiple CT scans during the period.

5 months after the diagnosis, the patient was re-hospitalized. Chest CT showed space-occupying lesions near the right pulmonary hilum (see Figure 1). Following consultations, the chest physicians consider the possibility of malignant lesions. Further, bronchoscopy could not be completed because the patient could not tolerate the procedure. As regards to the other examination results, the tumor indicators were normal, and acid-fast bacilli were not found in sputum specimen collected three times. Therefore, as extramedullary invasion of AML was speculated, chemotherapy with azacytidine 75 mg/m² on days 1–7, cisplatin 25 mg/m² on days 1–3, and etoposide 100 mg/m² on days 1–3 was initiated and supplemented with levofloxacin and fluconazole for antibiotics. Following treatment, the patient’s temperature remained normal for a week before discharge.

Figure 1.

Computed tomography of chest: (a) showing the right parahilar space occupying lesion 5 months after the diagnosis. (b) showing the lesions were more severe than before.

Six and a half months after the diagnosis, the patient was hospitalized due to “fever, cough, and expectoration for 4 days”, and bone marrow examination revealed complete remission of AML. Chest CT showed that the density of the right parahilar soft tissue and mediastinal enlargement of the fused lymph nodes had remained unchanged. The patient’s cough improved after antibiotics treatment with cefoperazone sulbactam and levofloxacin, but he still had recurrent fever. Later, the sputum samples submitted for examination did not show acid fast bacilli and were negative for the purified protein derivatives test and positive for T-cell spot of TB test. Therefore, moxifloxacin plus amikacin plus rifampicin were administered as anti-inflammatory and anti-tuberculosis agents, and voriconazole was included for empirical anti-fungal treatment. Half a month later, the chest CT showed that the lesions had become more severe than before (see Figure 1). Subsequently, the sputum sample was sent multiple times for detection of acid-fast bacilli, and acid-fast bacilli were detected. Simultaneously, ultrasonic tracheoscopy was performed, which showed black and white dead objects attached to the lumen of the right middle lobe of the right bronchus. Bronchoscopy brushing showed ciliated columnar epithelial cells and inflammatory exudates, and no tumor cells were found. Tracheoscopy biopsy showed small amounts of bronchial mucosa and cartilage, large numbers of lymphocytes and neutrophils were seen in the stroma, and some necrotic tissues were also found (see Figure 2). Acid-fast staining was positive (see Figure 3). Considering that acid-fast bacilli were detected in the sputum and biopsy tissue of the tracheoscope puncture, and as no tumor evidence was indicated, the diagnosis of pulmonary tuberculosis was clear. Thereafter, the patient was transferred to a specialized tuberculosis hospital and received four drug regimes for pulmonary tuberculosis that included isoniazid, rifampicin, pyrazinamide, and ethambutol. Unfortunately, 4 months later, the patient died due to uncontrollable tuberculosis and respiratory failure. The overall survival was 9 months.

Figure 2.

Ultrasonic tracheoscopy: Black and white dead objects seen attached to the lumen of the right middle lobe of the right bronchus.

Figure 3.

Tracheoscopy biopsy: Small amounts of bronchial mucosa and cartilage, large numbers of lymphocytes and neutrophils seen in the stroma, and some necrotic tissues also found (a). Acid fast bacilli staining test is positive (b). (Hematoxylin and eosin staining original magnification: ×200. Acid fast staining original magnification: ×400).

Discussion

In particular, if associated with tuberculosis infection, hematological malignancies are often fatal. Some studies have reported AML to be more prone to tuberculosis infection in comparison to other hematological malignancies, such as acute lymphoblastic leukemia and lymphoma.^1,2 It can precede, occur simultaneously or even during treatment of hematological malignancies. ³ In the study by Jain et al., the median interval between tuberculosis and AML diagnosis was about 13 weeks. ¹ Among these, 57.1% patients developed tuberculosis during the induction chemotherapy. Prolonged fever is one of the key presentations of tuberculosis among patients with hematological malignancy. ⁴ Therefore, the possibility of tuberculosis infection in patients with persistent fever during chemotherapy should be considered. This is consistent with the patient in this study. In addition, we found that the neutrophil count in this patient was constantly below 1x10⁹/L since the end of the first consolidation treatment, which may also be one of the factors leading to re-activation of tuberculosis. Moreover, cigarette smoke exposure is a key risk factor for both active and latent tuberculosis and may lead to adverse neurodevelopmental consequences in children.^5,6

The usual therapy of tuberculosis relies on the use of four anti-tuberculosis medications. Drug related adverse reactions should be closely monitored during treatment including fever, leucopoenia, allergic reactions, agranulocytosis, and an elevation of liver enzymes. ⁷

Conclusion

In cases wherein AML patients have persistent fever or pulmonary space-occupying lesions of unknown causes during chemotherapy, the possibility of tuberculosis should be considered after excluding common infections, autoimmune diseases, tumors. Early diagnosis and targeted anti-tuberculosis treatment may significantly improve the prognosis of patients.