title: 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.
authors.affiliation: Mayo Clinic College of Medicine, Rochester, MN, USA.
authors.forename: Paolo
authors.initials: P
authors.lastname: Strati
authors.affiliation: Mayo Clinic College of Medicine, Rochester, MN, USA.
authors.forename: Joon H
authors.initials: JH
authors.lastname: Uhm
authors.affiliation: Mayo Clinic College of Medicine, Rochester, MN, USA.
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Kaufmann
authors.affiliation: University of Chicago, IL, USA.
authors.forename: Chadi
authors.initials: C
authors.lastname: Nabhan
authors.affiliation: Mayo Clinic College of Medicine, Rochester, MN, USA.
authors.forename: Sameer A
authors.initials: SA
authors.lastname: Parikh
authors.affiliation: Mayo Clinic College of Medicine, Rochester, MN, USA.
authors.forename: Curtis A
authors.initials: CA
authors.lastname: Hanson
authors.affiliation: Mayo Clinic College of Medicine, Rochester, MN, USA.
authors.forename: Kari G
authors.initials: KG
authors.lastname: Chaffee
authors.affiliation: Mayo Clinic College of Medicine, Rochester, MN, USA.
authors.forename: Timothy G
authors.initials: TG
authors.lastname: Call
authors.affiliation: Mayo Clinic College of Medicine, Rochester, MN, USA shanafelt.tait@mayo.edu.
authors.forename: Tait D
authors.initials: TD
authors.lastname: Shanafelt
mesh_terms: D051997:ADP-ribosyl Cyclase 1 / Q000134:cerebrospinal fluid / Q000235:genetics; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000134:cerebrospinal fluid* / Q000235:genetics; D002452:Cell Count; D002490:Central Nervous System / Q000378:metabolism* / Q000473:pathology; D016543:Central Nervous System Neoplasms / Q000134:cerebrospinal fluid / Q000175:diagnosis* / Q000235:genetics / Q000401:mortality; D003937:Diagnosis, Differential; D005260:Female; D005434:Flow Cytometry; D022861:Hermanski-Pudlak Syndrome / Q000134:cerebrospinal fluid / Q000175:diagnosis* / Q000235:genetics / Q000401:mortality; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000134:cerebrospinal fluid / Q000235:genetics; D007153:Immunologic Deficiency Syndromes / Q000134:cerebrospinal fluid / Q000175:diagnosis* / Q000235:genetics / Q000401:mortality; D039441:Integrin alpha4 / Q000134:cerebrospinal fluid / Q000235:genetics; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000134:cerebrospinal fluid / Q000175:diagnosis* / Q000235:genetics / Q000401:mortality; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D000081207:Primary Immunodeficiency Diseases; D012189:Retrospective Studies; D013129:Spinal Puncture; D016019:Survival Analysis; D051746:ZAP-70 Protein-Tyrosine Kinase / Q000134:cerebrospinal fluid / Q000235:genetics
chemical_list: D014408:Biomarkers, Tumor; D007143:Immunoglobulin Heavy Chains; D039441:Integrin alpha4; D051746:ZAP-70 Protein-Tyrosine Kinase; C497261:ZAP70 protein, human; D051997:ADP-ribosyl Cyclase 1
references.citation: Mayo Clin Proc. 2000 Oct;75(10):1039-54
references.pmid: 11040852
references.citation: Neurology. 2008 Sep 30;71(14):1102-8
references.pmid: 18824675
references.citation: Acta Haematol. 1992;88(1):37-40
references.pmid: 1414160
references.citation: J Comput Assist Tomogr. 1990 Mar-Apr;14(2):255-61
references.pmid: 2312855
references.citation: Leuk Lymphoma. 2005 Nov;46(11):1593-8
references.pmid: 16236614
references.citation: Lancet. 1974 Feb 9;1(7850):211-2
references.pmid: 4129892
references.citation: Cancer. 1989 Sep 15;64(6):1296-300
references.pmid: 2766225
references.citation: Blood. 2015 Oct 1;126(14):1695-8
references.pmid: 26239089
references.citation: Acta Pathol Microbiol Immunol Scand A. 1983 Jul;91(4):209-16
references.pmid: 6575578
references.citation: N Engl J Med. 2005 Feb 24;352(8):804-15
references.pmid: 15728813
references.citation: Neuro Oncol. 2010 Apr;12(4):409-17
references.pmid: 20308318
references.citation: Cytometry B Clin Cytom. 2005 Jan;63(1):23-7
references.pmid: 15624205
references.citation: Clin Lymphoma Myeloma Leuk. 2010 Feb;10(1):E1-9
references.pmid: 20223720
references.citation: Leuk Lymphoma. 2002 Jan;43(1):199-201
references.pmid: 11908730
references.citation: Br J Haematol. 1999 Mar;104(4):689-94
references.pmid: 10192427
references.citation: Clin Neuropathol. 1990 Sep-Oct;9(5):224-30
references.pmid: 2272142
references.citation: Leuk Res. 2014 Mar;38(3):299-303
references.pmid: 24064196
references.citation: Neurology. 2010 Oct 12;75(15):1326-32
references.pmid: 20938025
references.citation: Neurology. 1996 Jan;46(1):19-25
references.pmid: 8559372
references.citation: Best Pract Res Clin Haematol. 2012 Mar;25(1):119-30
references.pmid: 22409828
references.citation: J Neurooncol. 2007 Jul;83(3):325-8
references.pmid: 17570037
references.citation: Acta Neurol Scand. 1979 Dec;60(6):363-70
references.pmid: 297427
references.citation: J Neurooncol. 1993 Apr;16(1):35-7
references.pmid: 8410140
references.citation: J Neurol Sci. 2009 Feb 15;277(1-2):130-2
references.pmid: 19100998
references.citation: Presse Med. 1983 Oct 22;12(37):2323-5
references.pmid: 6226982
references.citation: Leuk Lymphoma. 1998 Feb;28(5-6):603-5
references.pmid: 9613992
references.citation: J Clin Oncol. 2013 Jun 10;31(17):e280-2
references.pmid: 23650405
references.citation: Cancer. 1987 Aug 15;60(4):827-37
references.pmid: 3474054
references.citation: Zhonghua Xue Ye Xue Za Zhi. 2014 Jul;35(7):592-5
references.pmid: 25052598
references.citation: Aust N Z J Med. 1982 Jun;12(3):286-7
references.pmid: 6981407
references.citation: J Formos Med Assoc. 2000 Oct;99(10):775-8
references.pmid: 11061073
references.citation: Hematol Cell Ther. 1999 Aug;41(4):183-6
references.pmid: 10543375
references.citation: Am J Hematol. 2005 Dec;80(4):271-81
references.pmid: 16315252
references.citation: Lancet Oncol. 2015 Jul;16(7):e322-32
references.pmid: 26149884
references.citation: Int J Hematol. 2007 May;85(4):323-5
references.pmid: 17483076
references.citation: Ann Hematol. 2002 Jul;81(7):402-4
references.pmid: 12185514
references.citation: Neurology. 2015 Jan 20;84(3):325-6
references.pmid: 25527263
references.citation: Neurology. 1997 Feb;48(2):407-12
references.pmid: 9040730