title: Management of central nervous system involvement in chronic lymphocytic leukaemia: a retrospective cohort of 30 patients.
abstract: Central nervous system involvement (CNSi) is a rare and poorly reported complication of chronic lymphocytic leukaemia (CLL). Establishing cause and effect between the CLL and the neurological symptoms remains challenging. We have analysed a retrospective cohort of 30 CLL patients with CNSi, documented by lymphocytic infiltration either by flow cytometry of the cerebrospinal fluid (CSF; n = 29) or CNS biopsy (n = 1). Neurological symptoms were heterogeneous. At the time of CNSi, less than half of the patients had a progressive CLL and 20 had never been treated for CLL. Initial treatment with fludarabine-based immuno-chemotherapy, with or without intra-CSF therapy, led to durable response in eight out of nine untreated patients. In contrast, 50% patients receiving various prior treatments needed additional therapy within a median of 4 months (1-16). Ibrutinib led to complete response in 4/4 heavily pre-treated patients. From CNSi, 5-year overall survival was 72% and 48% for treatment-naïve and previously treated patients respectively (P = 0·06); 5-year progression-free survival (PFS) was 43% and 0% (P = 0·125). 17p deletion was significantly associated with poor PFS (P = 0·006). CNSi may be the only sign of progression of CLL and should be considered an initiation criterion of systemic treatment. Prognosis seemed to be related to CLL characteristics rather than to CNSi itself.
authors.affiliation: Department of Haematology, Institut Paoli-Calmettes, Marseille, France.
authors.forename: Anne
authors.initials: A
authors.lastname: Wanquet
authors.affiliation: Department of Haematology, Hôpital La Pitié-Salpêtrière, AP-HP, Paris, France.
authors.forename: Rudy
authors.initials: R
authors.lastname: Birsen
authors.affiliation: Department of Neurological Surgery, CHU Bordeaux, Bordeaux, France.
authors.forename: Charlotte
authors.initials: C
authors.lastname: Bonnet
authors.affiliation: URC/CRC, Hôpital Avicenne, AP-HP, Bobigny, France.
authors.forename: Marouane
authors.initials: M
authors.lastname: Boubaya
authors.affiliation: Department of Haematology, Hôpital La Pitié-Salpêtrière, AP-HP, Paris, France.
authors.forename: Sylvain
authors.initials: S
authors.lastname: Choquet
authors.affiliation: Lymphoid Malignancies Unit, Henri Mondor University Hospital, AP-HP, Créteil, France.
authors.forename: Jehan
authors.initials: J
authors.lastname: Dupuis
authors.affiliation: Department of Haematology, Centre Henri Becquerel, Rouen, France.
authors.forename: Stephane
authors.initials: S
authors.lastname: Lepretre
authors.affiliation: Department of Medicine 3, Centre Hospitalier, Antibes, France.
authors.forename: Daniel
authors.initials: D
authors.lastname: Re
authors.affiliation: Department of Haematology, CHU, Angers, France.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Fahri
authors.affiliation: Department of Haematology, Centre Léon Bérard, Lyon, France.
authors.forename: Anne-Sophie
authors.initials: AS
authors.lastname: Michallet
authors.affiliation: Department of Haematology, CHU, Toulouse, France.
authors.forename: Loïc
authors.initials: L
authors.lastname: Ysebaert
authors.affiliation: Service de thérapie cellulaire et d'hématologie clinique adulte CHU Clermont-Ferrand, Clermont-Ferrand, France.
authors.forename: Richard
authors.initials: R
authors.lastname: Lemal
authors.affiliation: Department of Haematology, CHU, Rennes, France.
authors.forename: Thierry
authors.initials: T
authors.lastname: Lamy
authors.affiliation: Department of Haematology, Hôpital Necker, AP-HP, Paris, France.
authors.forename: Richard
authors.initials: R
authors.lastname: Delarue
authors.affiliation: Department of Haematology, CHU, Caen, France.
authors.forename: Xavier
authors.initials: X
authors.lastname: Troussard
authors.affiliation: URC/CRC, Hôpital Avicenne, AP-HP, Bobigny, France.
authors.forename: Florence
authors.initials: F
authors.lastname: Cymbalista
authors.affiliation: URC/CRC, Hôpital Avicenne, AP-HP, Bobigny, France.
authors.forename: Vincent
authors.initials: V
authors.lastname: Levy
authors.affiliation: Centre of Oncology, Hôpitaux Universitaires, Geneva, Switzerland.
authors.forename: Pierre-Yves
authors.initials: PY
authors.lastname: Dietrich
authors.affiliation: Department of Haematology, Hôpital La Pitié-Salpêtrière, AP-HP, Paris, France.
authors.forename: Veronique
authors.initials: V
authors.lastname: Leblond
authors.affiliation: Department of Haematology, Institut Paoli-Calmettes, Marseille, France.
authors.forename: Therese
authors.initials: T
authors.lastname: Aurran-Schleinitz
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D002490:Central Nervous System / Q000473:pathology*; D015331:Cohort Studies; D019468:Disease Management; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000150:complications / Q000188:drug therapy / Q000401:mortality / Q000473:pathology*; D017254:Leukemic Infiltration / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D010880:Piperidines; D011379:Prognosis; D011720:Pyrazoles / Q000627:therapeutic use; D011743:Pyrimidines / Q000627:therapeutic use; D012074:Remission Induction; D012189:Retrospective Studies; D016019:Survival Analysis; D014740:Vidarabine / Q000031:analogs & derivatives / Q000627:therapeutic use
chemical_list: D010880:Piperidines; D011720:Pyrazoles; D011743:Pyrimidines; C551803:ibrutinib; D014740:Vidarabine; D000225:Adenine; C024352:fludarabine
keywords: 
  cerebrospinal fluid
  ; central nervous system; chronic lymphocytic leukaemia; magnetic resonance imaging; treatment