Cryptococcus neoformans in Chronic Lymphocytic Leukemia (CLL) Treated With Ibrutinib: A Combo Gone Wrong!

A 71-year-old female, with hypertension, depression, and asthma, was diagnosed with chronic lymphocytic leukemia (CLL) (elevated beta-2 microglobulin and deletion of 13 q chromosome) and treated with ibrutinib. She had general weakness, dyspnea, fatigue, shortness of breath, upper abdominal fullness, and discomfort from splenomegaly. In the ED, her oxygen saturation (SpO₂) was 83% on room air, afebrile, and stable. Nasal oxygen at 3 L improved her hypoxemia and symptoms. An exam showed bilateral crackles, systolic murmur 2/6, non-tender abdomen with splenomegaly, and no lower extremities edema. A CT scan showed patchy ground glass opacities, interlobular septal thickening, and bilateral pleural effusion. Diuretics were given, but the patient's condition worsened, requiring ICU and bi-level positive airway pressure (BiPAP). Staphylococcus hominis was found in blood cultures, and vancomycin was started. Respiratory distress necessitated mechanical ventilation and intubation. Imaging suggested acute respiratory distress syndrome (ARDS), atypical pneumonia, or heart failure with preserved ejection fraction. Transthoracic echocardiogram showed normal ejection fraction with severely increased pulmonary artery pressure, and transesophageal echocardiogram showed no vegetation. Blood cultures monitored the Gram-positive bacteremia, with BioFire isolating Candida zeylanoides initially. Subsequent cultures over a week period were positive for C. zeylanoides and then Cryptococcus neoformans. Chest CT revealed a large mass of lymph nodes in the mediastinal area, which was thought to be causing pulmonary hypertension by compressing the pulmonary artery. After a multidisciplinary discussion, ibrutinib was withheld, and drug-induced pneumonitis was suspected. Fungemia was found in the immunocompromised patient, so the infectious disease team prescribed voriconazole for 13 days and then changed to amphotericin and fluconazole due to a lack of improvement. Eye examination showed no signs of endophthalmitis. Lumbar puncture showed no central nervous system (CNS) fungal infection. The patient's respiratory status worsened, so a bronchoscopy with bronchoalveolar lavage (BAL) of the right middle lobe and chest tube placement for pleural effusion was done. Microbiological examination of BAL and pleural effusion revealed C. neoformans and Klebsiella, confirming disseminated C. neoformans. Despite a tough 32-day hospital stay, the patient was discharged in stable condition. Physical therapy and nutrition optimization were used to enhance her health. This case report highlights the rare but serious complication of cryptococcal disease in patients using ibrutinib for blood cancers. Early comprehensive diagnosis and multi-disciplinary involvement saved our patient's life.