PNEUMONITIS SECONDARY TO EBV-SPECIFIC CYTOTOXIC T-LYMPHOCYTES

Abstract

SESSION TITLE: Diffuse Lung Disease 1 SESSION TYPE: Fellow Case Reports PRESENTED ON: 10/07/2018 03:30 pm - 04:30 pm INTRODUCTION: Novel immune based therapies are now being used for a wide range of malignancies including post-transplantation lymphoproliferative disorders (PTLD), however, the short and long term risk of these therapies remains unclear. Here, we present a case of a patient who developed hypoxemia one day after receiving an infusion of EBV-specific cytotoxic T-lymphocytes. CASE PRESENTATION: A 66-year-old male presented to the hospital with 4 days of progressive dyspnea, cough, and hypoxemia. He had a history of end stage renal disease and EBV-positive cadaveric renal transplantation which was complicated by EBV viremia and PTLD. Two months prior, the patient began therapy with HLA-matched EBV-specific T-lymphocytes after failing several immunosuppressive and chemotherapeutic regimens. His most recent infusion was 1 day prior to symptom onset. On admission, oxygen saturation was 91% on room air and 96% on 2 liters of oxygen by nasal cannula. Physical exam at that time was notable for faint crackles throughout all lung fields. Chest radiograph was negative for infiltrates or effusions although computed tomography imaging of the chest revealed diffuse bilateral ground glass opacities and patchy airspace disease with an upper lobe predominance (see Figure 1). Bronchoscopy with transbronchial biopsy revealed interstitial inflammation and fibrosis, hyperplasia of type II pneumocytes, and scattered foci of organizing pneumonia consistent with active pneumonitis. Bronchoalveolar lavage demonstrated a lymphocyte predominant cell distribution with 56% lymphocytes, 41% macrophages, and 3% neutrophils. BAL and biopsy were negative for viral, fungal, and bacterial elements. With supportive care alone, the patient improved over the course of 5 days and was discharged to a short term rehabilitation facility. DISCUSSION: PTLD is a serious complication for patients undergoing organ transplantation. EBV-specific cytotoxic T-cells have shown promising results in the treatment of some of these patients, however, emerging evidence suggests that pulmonary complications are a consequence of this therapy. Indeed, in a series of 39 patients there was 1 reported death due to pneumonitis. Moreover, outcomes in another study of 114 patients found that 1 patient developed severe pulmonary infiltrates within one week of receiving EBV-specific T-cells. This patient did not suffer long-term sequelae from this complication. Our case suggests that pneumonitis from EBV-specific T-lymphocytes is characterized by a histopathological pattern of organizing pneumonia and a lymphocyte predominant cellular distribution. CONCLUSIONS: EBV-specific cytotoxic T-cell therapy causes acute pneumonitis in some patients. Additional studies will be important to understand the true incidence of pneumonitis after EBV-specific therapies, and for determining the factors that predispose or prevent the development of this therapeutic complication. Reference #1: Heslop, H. E., Slobod, K. S., Pule, M. A., et al. Long-term outcome of EBV-specific T-cell infusions to prevent or treat EBV-related lymphoproliferative disease in transplant recipients. Blood. 2010; 115(5):925-935. Reference #2: Rooney, C. M., Smith, C. A., Ng, C. Y., et al. Infusion of Cytotoxic T Cells for the Prevention and Treatment of Epstein-Barr Virus–Induced Lymphoma in Allogeneic Transplant Recipients. Blood. 1998; 92(5):1549-1555. Reference #3: Dierickx, D., and Habermann, T.M. Post-Transplantation Lymphoproliferative Disorders in Adults. N Engl J Med. 2018; 378:549-562. DISCLOSURES: No relevant relationships by Robert Hilton, source=Web Response No relevant relationships by Carl Nieweld, source=Web Response No relevant relationships by ross summer, source=Web Response