Prevalence and characteristics of central nervous system involvement by chronic lymphocytic leukemia

Abstract

Abroad array of conditions can lead to neurological symptoms in chronic lymphocytic leukemia patients and distinguishing between clinically significant involvement of the central nervous system by chronic lymphocytic leukemia and symptoms due to other etiologies can be challenging. Between January 1999 and November 2014, 172 (4%) of the 4174 patients with chronic lymphocytic leukemia followed at our center had a magnetic resonance imaging of the central nervous system and/or a lumbar puncture to evaluate neurological symptoms. After comprehensive evaluation, the etiology of neurological symptoms was: central nervous system chronic lymphocytic leukemia in 18 patients (10% evaluated by imaging and/or lumbar puncture, 0.4% overall cohort); central nervous system Richter Syndrome in 15 (9% evaluated, 0.3% overall); infection in 40 (23% evaluated, 1% overall); autoimmune/inflammatory conditions in 28 (16% evaluated, 0.7% overall); other cancer in 8 (5% evaluated, 0.2% overall); and another etiology in 63 (37% evaluated, 1.5% overall). Although the sensitivity of cerebrospinal fluid analysis to detect central nervous system disease was 89%, the specificity was only 42% due to the frequent presence of leukemic cells in the cerebrospinal fluid in other conditions. No parameter on cerebrospinal fluid analysis (e.g. total nucleated cells, total lymphocyte count, chronic lymphocytic leukemia cell percentage) were able to offer a reliable discrimination between patients whose neurological symptoms were due to clinically significant central nervous system involvement by chronic lymphocytic leukemia and another etiology. Median overall survival among patients with clinically significant central nervous system chronic lymphocytic leukemia and Richter syndrome was 12 and 11 months, respectively. In conclusion, clinically significant central nervous system involvement by chronic lymphocytic leukemia is a rare condition, and neurological symptoms in patients with chronic lymphocytic leukemia are due to other etiologies in approximately 80% of cases. Analysis of the cerebrospinal fluid has high sensitivity but limited specificity to distinguish clinically significant chronic lymphocytic leukemia involvement from other etiologies.

Figure 1.

Diagnostic work up performed for neurological symptoms in this cohort of patients with chronic lymphocytic leukemia. CLL: chronic lymphocytic leukemia; SLL: small lymphocytic lymphoma; MRI: magnetic resonance imaging; LP: lumbar puncture; CNS: central nervous system.

Figure 2.

Magnetic resonance findings. (A) Chronic lymphocytic leukemia (CLL) parenchymal. (B) CLL meningeal. (C) Richter syndrome (RS) parenchymal. (D) RS meningeal.

Figure 3.

Overall survival (OS) by final diagnosis of etiology of neurological symptoms. *Clinically significant chronic lymphocytic leukemia (see Methods).

Figure 4.

Diagnostic work up of neurological symptoms in patients with chronic lymphocytic leukemia. CNS: central nervous system; LP: lumbar puncture; PCR: polymerase chain reaction; CSF: cerebrospinal fluid; Ab: antibodies; NLP: neoplastic. ¹PCR for viruses to include JC, WNL, HHV-6, EBV, VZV and CMV. Fungal antigens (both on CSF and blood) to include cryptococcus and coccidioides. ²CSF evaluation to include oligoclonal bands; serum markers to include p-ANCA, c-ANCA, anti-acetylcholine receptor and ACE.