title: Ki-67 is a strong predictor of central nervous system relapse in patients with mantle cell lymphoma (MCL).
abstract: BACKGROUND
  Central nervous system (CNS) relapse is an uncommon but challenging complication in patients with mantle cell lymphoma (MCL). Survival after CNS relapse is extremely poor. Identification of high-risk populations is therefore critical in determining patients who might be candidates for a prophylactic approach.
  
  
  METHODS
  A total of 608 patients (median age, 67 years; range 22-92) with MCL newly diagnosed between 1994 and 2012 were evaluated. Pretreatment characteristics and treatment regimens were evaluated for their association with CNS relapse by competing risk regression analysis.
  
  
  RESULTS
  None of the patients received intrathecal prophylaxis. Overall, 33 patients (5.4%) experienced CNS relapse during a median follow-up of 42.7 months. Median time from diagnosis to CNS relapse was 20.3 months (range: 2.2-141.3 months). Three-year cumulative incidence of CNS relapse was 5.6% [95% confidence interval (95% CI) 3.7% to 8.0%]. Univariate analysis revealed several risk factors including blastoid variant, leukemic presentation, high-risk MCL International Prognostic Index and high Ki-67 (proliferation marker). Multivariate analyses revealed that Ki-67 ≥ 30 was the only significant risk factor for CNS relapse (hazard ratio: 6.0, 95% CI 1.9-19.4, P = 0.003). Two-year cumulative incidence of CNS relapse in patients with Ki-67 ≥ 30 was 25.4% (95% CI 13.5-39.1), while that in the patients with Ki-67 < 30 was 1.6% (95% CI 0.4-4.2). None of the treatment modalities, including rituximab, high-dose cytarabine, high-dose methotrexate or consolidative autologous stem-cell transplant, were associated with a lower incidence of CNS relapse. Survival after CNS relapse was poor, with median survival time of 8.3 months. There was no significant difference in the survival by the site of CNS involvement.
authors.affiliation: Department of Lymphoma and Myeloma, MD Anderson Cancer Center, Houston, USA; Division of Epidemiology and Prevention, Aichi Cancer Center Research Institute, Nagoya. Electronic address: dchihara-kob@umin.ac.jp.
authors.forename: D
authors.initials: D
authors.lastname: Chihara
authors.affiliation: Department of Pathology and Clinical Laboratories, Nagoya University Graduate School of Medicine, Nagoya.
authors.forename: N
authors.initials: N
authors.lastname: Asano
authors.affiliation: Department of Hematology and Oncology, Tokai University School of Medicine, Isehara.
authors.forename: K
authors.initials: K
authors.lastname: Ohmachi
authors.affiliation: Department of Hematology and Oncology, Kyoto University Graduate School of Medicine, Kyoto.
authors.forename: M
authors.initials: M
authors.lastname: Nishikori
authors.affiliation: Department of Hematology and Medical Oncology, Fujita Health University School of Medicine, Toyoake.
authors.forename: M
authors.initials: M
authors.lastname: Okamoto
authors.affiliation: Department of Hematology and Oncology, Anjo Kosei Hospital, Anjo.
authors.forename: M
authors.initials: M
authors.lastname: Sawa
authors.affiliation: Department of Medical Oncology, Kanagawa Cancer Center, Yokohama.
authors.forename: R
authors.initials: R
authors.lastname: Sakai
authors.affiliation: Department of Hematology, Faculty of Medicine, University of Tsukuba, Tsukuba.
authors.forename: Y
authors.initials: Y
authors.lastname: Okoshi
authors.affiliation: Department of Medicine and Clinical Science, Gunma University Graduate School of Medicine, Gunma.
authors.forename: N
authors.initials: N
authors.lastname: Tsukamoto
authors.affiliation: Department of Clinical Oncology, Ehime University Graduate School of Medicine, Ehime.
authors.forename: Y
authors.initials: Y
authors.lastname: Yakushijin
authors.affiliation: Department of Pathology and Clinical Laboratories, Nagoya University Graduate School of Medicine, Nagoya.
authors.forename: S
authors.initials: S
authors.lastname: Nakamura
authors.affiliation: Department of Hematology and Cell Therapy, Aichi Cancer Center Hospital, Nagoya.
authors.forename: T
authors.initials: T
authors.lastname: Kinoshita
authors.affiliation: Department of Hematology and Laboratory Medicine, Suzuka National Hospital, Suzuka.
authors.forename: M
authors.initials: M
authors.lastname: Ogura
authors.affiliation: Department of HSCT Data Management and Biostatistics, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: R
authors.initials: R
authors.lastname: Suzuki
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016543:Central Nervous System Neoplasms / Q000737:chemistry* / Q000401:mortality / Q000473:pathology / Q000628:therapy; D005260:Female; D006801:Humans; D015994:Incidence; D007564:Japan / Q000453:epidemiology; D053208:Kaplan-Meier Estimate; D019394:Ki-67 Antigen / Q000032:analysis*; D020522:Lymphoma, Mantle-Cell / Q000737:chemistry* / Q000401:mortality / Q000473:pathology / Q000628:therapy; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D011237:Predictive Value of Tests; D012008:Recurrence; D012189:Retrospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D019394:Ki-67 Antigen
keywords: CNS relapse; Ki-67; mantle cell lymphoma; risk factors