Fatal Interstitial Pneumonitis Rapidly Developed after the First Cycle of CHOP with Etoposide Combination Chemotherapy in a Patient with Lymphoma
A 69-year-old man was admitted to the hospital presenting with multiple palpable masses in the neck and groin area. He had hypertension and a 30-pack year smoking history. The Eastern Cooperative Oncology Group performance status was grade 2, and lactate dehydrogenase level was 824 IU/L (normal, 218-472 IU/L) at diagnosis. A lymph node biopsy was performed in the right groin, and the patient was diagnosed with PTCL, NOS. Further, neck, chest, and abdominal computed tomography (CT), positron emission tomography/computed tomography, and bone marrow examination were conducted for the staging work-up. Lymphomatous involvements were found in the tonsil, spleen, left anterior chest wall, ileocecal area, and multiple lymph nodes on both sides of the diaphragm (). However, no involvement in the bone marrow was noted. The initial chest CT scan showed multiple lymphadenopathies and, incidentally, diffuse centrilobular emphysema (). Finally, the patient was diagnosed with Ann Arbor stage IV PTCL, NOS and he was considered to be at high risk according to the international prognostic index. He received the first cycle of CHOP with etoposide combination chemotherapy (750 mg/m2 cyclophosphamide i.v. on day 1 [D1], 1.4 mg/m2 vincristine i.v. on D1, 50 mg/m2 doxorubicin i.v. on D1, 60 mg/m2 prednisolone p.o. on D1-5, and etoposide 100 mg/m2 i.v. on D1). Eight days after the chemotherapy, he developed a neutropenia, and, then, lenograstim (5 µg/kg, i.v.) was administered for 7 consecutive days. The second cycle of chemotherapy was delayed for 1 week because he had developed a moderate degree of small bowel bleeding while recovering from the neutropenia; the bleeding was controlled by supportive care only.\nAfter 30 days of the first cycle of combination chemotherapy, the patient was hospitalized for the second cycle of CHOP with etoposide chemotherapy. Unfortunately, he complained of exertional dyspnea and shortness of breath without fever or purulent sputum. Crackles were noted in both lower lung fields on chest auscultation. The initial laboratory examination revealed a white blood cell count of 12,900/µL, hemoglobin level of 12.9 g/dL, and platelet count of 328,000/µL. The level of C-reactive protein was 14.31 mg/dL. Arterial blood gas analysis (ABGA) with 2 L/min oxygen administered via nasal prongs showed that the pH was 7.489, PaO2 75.9 mm Hg, PaCO2 28.4 mm Hg, bicarbonate level 21.1 mmol/L, and SaO2 96.3%, showing respiratory alkalosis. A chest X-ray showed diffuse ground glass appearances with reticulation in both lungs (). A chest CT scan showed to the markedly improvements of previous multiple lymphomatous involvements in the thorax, but it also revealed that both lungs had a newly developed peripherally predominant diffuse ground glass appearance with reticulation ().\nFor evaluation of associated pulmonary infection, the patient was performed the rapid influenza antigen immunoassays that can identify influenza A and B viral nucleoprotein antigens, sputum culture for the evaluation of bacterial pneumonia, acid-fast bacillus (AFB) smear, Mycobacterium tuberculosis polymerase chain reaction (PCR) test and Pneumocystis PCR in the sputum. Additionally, we checked the serum galactomannan assay for screening of aspergillosis infection before treatment of antibiotics. The influenza A or B antigen immunoassay, AFB stain, M. tuberculosis PCR test and Pneumocystis PCR were all negative and bacteria was not cultured in the respiratory specimen. The galactomannan assay showed the negative result (0.1 optical density index) and there was no objective evidence about pulmonary infection. Further diagnostic studies such as bronchoalveolar lavage (BAL) or lung biopsy were not performed because the symptom of dyspnea was deteriorated. Based on the clinical status and the radiological finding, the patient was diagnosed with drug-induced interstitial pneumonitis, and 125 mg/day prednisone was administered immediately with the empirical antibiotics such as tazobactam and clarithromycin. After the 15th day of prednisone therapy, a chest CT scan showed no changes, and a small amount of pneumomediastinum had newly developed (). After the 32th day of prednisone treatment, the symptoms of dyspnea were aggravated up to grade 4 according to the Medical Research Council Dyspnea Scale, and a chest X-ray showed diffuse interstitial lung infiltration throughout the entire lung (). At that time, we did not check the additional evaluations, such as Pneumocystis PCR or BAL study, because of the worsened his condition. ABGA showed that the patient was experiencing respiratory distress as his PaO2 was 59.6 mm Hg with 10 L/min oxygen supply via mask. Therefore, 375 mg/day prednisone was administered, but the patient died of respiratory failure on the 38th day after the treatment of prednisone.