3.26 Central Nervous System Infiltration in a Patient with Chronic Lymphocytic Leukemia

Abstract

Central nervous system (CNS) primary or secondary involvement in the presence of lymphoma cells in cerebrospinal fluid and/or focal changes in the brain cells may be seen sporadically in chronic lymphocytic leukemia (CLL). The location of such changes may be life-threatening and thus requires urgent therapy. In the initial phase, CNS involvement may take the form of neurological symptoms (vertigo, headaches, confusion) or may have no symptoms whatsoever. The basic examination confirming CNS involvement comprises analysis of cerebrospinal fluid and MRI interpretation. Some diagnosticians believe that the presence of typical neurologic symptoms accompanied by MRI changes is consistent with CNS infiltration. Case: Sixty-four year old woman, was first diagnosed suffering from CLL in February 2008. Baseline symptoms were: anemia, peripheral lymphadenopathy, abdominal lymphadenopathy, hepatosplenomegaly, 85% bone marrow infiltration with small lymphocytes, ZAP 70 -10% in the flow cytometry, CD38-90%, 90% parenchymal infiltration in the bone biopsy. The regimen of FC (fludarabine + cyclophosphamide) was applied; this treatment was preceded by leukapheresis due to high leukocytosis, order of 600G/ l (lymphocytes 550G/ l). In July 2008, the patient's condition improved and residual disease was diagnosed. From that time on, until March 2011 the patient was treated under the care of the hematology out-patient clinic. Last March, the patient experienced dizziness, vertigo and visual disturbances. CNS MRI revealed a hyperintense focus,10 mm in diameter, at the pons on the right side; following contrast medium administration the lesion, in its focal part, was enhanced. The location of the changes made stereotactic biopsy impossible. The flow cytometry of cerebrospinal fluid disclosed no signs of infiltration with lymphoma cells. Based on MRI, a focal change was found, probably as a result of an underlying disease. The diagnostic tests performed confirmed the progression of chronic lymphocytic leukemia; 80% parenchymal infiltration with small lymphocytes was found in biopsy. It was decided to apply a treatment regimen of R-FC (fludarabine + rituximab + cyclophosphamide) - 6 cycles and intrathecal chemotherapy. Initially chemotherapy consisting of 15 mg intrathecal methotrexate, 40 mg cytarabine, 8 mg dexamethasone was administered, followed by 2 week intervals of DepoCyte 50 mg. In the follow-up MRI, after the 1st cycle of chemotherapy R-FC + DepoCyte almost complete resorption of CNS changes was seen. It was decided to continue the treatment (both chemotherapy R-FC and intrathecal administration of DepoCyte in accordance to generally accepted recommendations). Summary: Chronic lymphocytic leukemia, as indicated by reports, rarely originates from CNS involvement. In this case, we assumed that the outbreak detected by MRI in the pons is a dripstone in the course of the underlying disease. The author's findings were confirmed by the fact that applied treatment brought about the desired results.