Abstract Introduction Chylothorax is an uncommon pulmonary complication of chronic lymphocytic leukemia (CLL), typically due to thoracic duct obstruction or infiltration by malignant lymphocytes. Current guidelines recommend conservative management with dietary fat restriction, medium-chain triglycerides supplementation, octreotide, and thoracentesis, with options of thoracic duct embolization, surgical ligation, or pleurodesis if refractory 1. However, in neoplastic causes such as CLL, sustained resolution may require disease-directed therapy. Case Report A 53-year-old man with metabolic syndrome and diabetes presented initially with acute hypoxemic respiratory failure due to acute respiratory distress syndrome physiology, requiring intubation and ICU admission. In addition to the bilateral pulmonary infiltrates, imaging studies also revealed diffuse lymphadenopathy and splenomegaly. Right axillary node dissection confirmed CLL with expanded proliferation centers, trisomy 12, and TP53 deletion. After extubation, medical optimization, and discharge, he developed progressive cervical adenopathy six months later. Biopsies confirmed accelerated-phase CLL with high Ki-67 (80%), MYC overexpression, and over 80% p53 positivity, while Richter’s transformation was excluded. He declined oncology’s recommendation for systemic therapy with Zanubrutinib, a Bruton’s tyrosine kinase inhibitor. He was closely monitored, and his lymphadenopathy remained stable, with no evidence of disease progression. A year later, he was admitted with severe sepsis from a necrotic toe infection, with a white blood cell count peaking at 55K/µL. Shortly afterward, he developed acute respiratory failure in the setting of a large right pleural effusion. Pleural fluid was chylous, and cytology confirmed malignant lymphocytes. Guideline-based measures, including a strict nonfat diet, octreotide infusion, serial large-volume thoracenteses, and an indwelling pleural catheter, failed to control drainage. Zanubrutinib was ultimately started, and consequently, pleural output declined significantly, his oxygen requirement resolved, and the catheter was removed. He remained symptom-free on follow-up. Discussion Malignant chylothorax in CLL is rare. This complication should be recognized as a potential marker of CLL progression. As this case illustrates, refractory chylothorax in CLL poses significant management challenges and may not respond to guideline-based conservative or procedural therapies. Prolonged conservative management risks malnutrition, infections, and immunosuppression, and interventional options may not always be feasible 1. A definitive resolution in this patient occurred only after the initiation of targeted systemic therapy, emphasizing the importance of early multidisciplinary evaluation in CLL and the integration of targeted therapy into pulmonary and critical care management algorithms when standard approaches fail. Reference: 1. Bhatnagar, Malvika, et al. “Chylothorax: pathophysiology, diagnosis, and management—a comprehensive review.” Journal of Thoracic Disease, 16(2), Feb. 2024, https://doi.org/10.21037/jtd-23-1636 This abstract is funded by: None
Sorathia et al. (Fri,) studied this question.