CHRONIC LYMPHOCYTIC LEUKEMIA INVOLVEMENT OF CENTRAL NERVOUS SYSTEM: A SINGLE CENTRE EXPERIENCE

Abstract

Introduction: Chronic lymphocytic leukemia (CLL) involvement of central nervous system (CNS) is reported to be rare, mainly due to only occasional appear of predominantly non-specific neurological symptoms. Neurologic complications arising from direct leukemic involvement of CNS is stated in only 1% of patients (pts) with CLL. There is no treatment consensus with similar results of intrathecal chemotherapy or whole-brain irradiation, but some more recent studies reported more encouraging data with application of immunochemotherapy or tyrosine kinase inhibitor, ibrutinib. CLL with CNS involvement is related with poorer outcome, especially for pts with unfavorable cytogenetic (17p deletion). Methods: We presented a small series of four pts that were diagnosed and treated in our Institution. All pts met the International Workshop on CLL diagnostic criteria (2008). Diagnosis of CNS involvement was established via neuroimaging methods such as MRI, as well as cerebrospinal fluid (CSF) cytology, and CSF multiparameter flow cytometry immynophenotyping method (CSF FCM). Results: All pts were men with average age of 55.25 years (yrs). On CNS onset, all had disseminated disease and 17p deletion was registered in one case. Average latency period from CLL to CNS onset was 2.91 yrs. We registered heterogeneous neurological symptoms on CNS onset, including bradypsyhia, headaches, nausea, vomiting, dysphasia, repeated unconsciousness, urinary incontinence, dyslexia, lack of fine motor control, diplopia and bilateral eyelid swelling. Diagnostics included positive CSF cytology in three cases, CSF FCM was performed in all of our cases. MRI scan was performed in all cases and was conclusive in three (75%) cases. On CLL onset, two pts were treated with systemic chemotherapy, FC (fludarabine, cyclophosphamide) in one case and CHOP (cyclophosphamide, doxorubicine, vincristine, prednisolone) in other, third was initially treated with corticosteroid therapy due to immunological thrombocytopenia and fourth was on “watch and wait” policy, due to comorbidities. Two of our pts were treatment naïve on CNS onset. When CLL in CNS was diagnosed, systemic chemotherapy was applied in all cases. First patient received high-dose methotrexate with intrathecal therapies, second R(rituximab)-FC, and two received DHAP regimen (dexametasone, high-dose cytarabine, cisplatin) in two cases. Average and median OS from CNS onset was 4 and 3.5 months, respectively, with lethal outcome in 75% of cases in our follow-up. Conclusions: CLL in CNS is still rarely diagnosed, primarily due to the presence of heterogeneous, non-specific neurological symptoms, or their absence. The most effective diagnostics includes MRI, CSF-FCM, and if it is possible PCR detection of CLL cells in CSF. Our results confirm the poor therapeutic outcome and short survival in our group of pts. Keywords: chronic lymphocytic leukemia (CLL); flow cytometry; immunochemotherapy.