Unusual Relapse of Chronic Lymphocytic Leukemia After Remission

Chronic lymphocytic leukemia (CLL) is the most prevalent leukemia with over 20,000 estimated cases in 2017. Leukemic involvement of the nervous system from CLL causing neurologic symptoms is reported in only about one percent of patients. Unfortunately, there is no current standard therapy for the treatment of CLL leptomeningeal disease. In this case, we discuss an unusual presentation of CLL leptomeningeal disease misdiagnosed as chronic rebound headache. A 61-year-old female was diagnosed with Rai stage I CLL in 2002. She presented at that time with peripheral blood lymphocytosis and subsequent flow cytometry revealed a mature B cell population consistent with CLL. She was monitored clinically as there were no indications for therapy. In 2006, she developed B symptoms along with hemolytic anemia refractory to steroids and was initiated on chemotherapy with fludarabine, cyclophosphamide, and rituximab (FCR). She had a complete response after six cycles. The patient was in her usual state of health until 2016, when she complained of chronic headaches. She took acetaminophen and ibuprofen regularly and was diagnosed with rebound headaches by neurology. These symptoms progressed and the patient developed encephalopathy requiring inpatient admission. Magnetic resonance imaging (MRI) revealed abnormal enhancement in the cerebellar peduncles and dentate nuclei symmetrically; a lumbar puncture performed revealed evidence of CLL consistent with leptomeningeal disease. Therapy was started with oral ibrutinib at 560 mg daily for better central nervous system (CNS) penetration. After three months of therapy, she had complete resolution of symptoms and MRI abnormalities. Leptomeningeal disease is a rare complication of CLL that clinicians should be aware of and ibrutinib can be an effective, tolerable therapy for this debilitating disease.