title: Patterns of central nervous system involvement in relapsed and refractory multiple myeloma.
abstract: BACKGROUND
  Invasion of CNS in MM is an extremely rare occurrence that is associated with advanced disease with poor prognosis.
  
  
  METHODS
  Our MM database identified 35 CNS MM cases presenting between January 1996 and March 2012. Descriptive analyses were performed on available data on patient characteristics, disease course, and outcomes.
  
  
  RESULTS
  The mean age at diagnosis was 55.4 years; 23.5% (n = 8) patients had elevated levels of beta-2-microglobulin > 5.5 mg/L; 68.6% (n = 24) of patients had elevated lactate dehydrogenase (LDH) levels (≥ 2 times upper limit of normal); and 14% (n = 5) of patients had secondary plasma cell leukemia. Magnetic resonance imaging (MRI), which was performed in 34 patients, showed diffuse or localized leptomeningeal disease in 20 patients (58.8%). Monoclonal malignant plasma cells were found by CSF analysis in all 35 patients. In total, 31 patients received chemotherapy, including intrathecal chemotherapy as a part of their treatment, with a median survival of 4 months after CNS MM diagnosis.
  
  
  CONCLUSIONS
  In our experience, CNS MM is an aggressive terminal disease feature associated with high beta-2-microglobulin level, high LDH level, and secondary plasma cell leukemia. This study highlights an unmet need in this subset of patients with high-risk, relapsed or refractory MM.
  
  
  CONCLUSIONS
  Achieving adequate CSF penetration while limiting the off-target effects needs to be considered in MM-specific novel drug development.
authors.affiliation: Myeloma Institute for Research and Therapy, University of Arkansas for Medical Sciences, Little Rock, AR.
authors.forename: Al-ola
authors.initials: AO
authors.lastname: Abdallah
authors.affiliation: Myeloma Institute for Research and Therapy, University of Arkansas for Medical Sciences, Little Rock, AR.
authors.forename: Shebli
authors.initials: S
authors.lastname: Atrash
authors.affiliation: Myeloma Institute for Research and Therapy, University of Arkansas for Medical Sciences, Little Rock, AR.
authors.forename: Zainab
authors.initials: Z
authors.lastname: Shahid
authors.affiliation: Myeloma Institute for Research and Therapy, University of Arkansas for Medical Sciences, Little Rock, AR.
authors.forename: Muzaffar
authors.initials: M
authors.lastname: Jameel
authors.affiliation: Myeloma Institute for Research and Therapy, University of Arkansas for Medical Sciences, Little Rock, AR.
authors.forename: Monica
authors.initials: M
authors.lastname: Grazziutti
authors.affiliation: Myeloma Institute for Research and Therapy, University of Arkansas for Medical Sciences, Little Rock, AR.
authors.forename: Senu
authors.initials: S
authors.lastname: Apewokin
authors.affiliation: Myeloma Institute for Research and Therapy, University of Arkansas for Medical Sciences, Little Rock, AR.
authors.forename: Naveen S
authors.initials: NS
authors.lastname: Kumar
authors.affiliation: Myeloma Institute for Research and Therapy, University of Arkansas for Medical Sciences, Little Rock, AR.
authors.forename: Alejandro
authors.initials: A
authors.lastname: Restrepo
authors.affiliation: Myeloma Institute for Research and Therapy, University of Arkansas for Medical Sciences, Little Rock, AR.
authors.forename: Sarah
authors.initials: S
authors.lastname: Waheed
authors.affiliation: Myeloma Institute for Research and Therapy, University of Arkansas for Medical Sciences, Little Rock, AR.
authors.forename: Frits
authors.initials: F
authors.lastname: Van Rhee
authors.affiliation: Myeloma Institute for Research and Therapy, University of Arkansas for Medical Sciences, Little Rock, AR.
authors.forename: Christoph J
authors.initials: CJ
authors.lastname: Heuck
authors.affiliation: Myeloma Institute for Research and Therapy, University of Arkansas for Medical Sciences, Little Rock, AR.
authors.forename: Donald
authors.initials: D
authors.lastname: Johann
authors.affiliation: Myeloma Institute for Research and Therapy, University of Arkansas for Medical Sciences, Little Rock, AR.
authors.forename: Bart
authors.initials: B
authors.lastname: Barlogie
authors.affiliation: Myeloma Institute for Research and Therapy, University of Arkansas for Medical Sciences, Little Rock, AR. Electronic address: saad.usmani@carolinashealthcare.org.
authors.forename: Saad Z
authors.initials: SZ
authors.lastname: Usmani
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001921:Brain / Q000473:pathology; D016543:Central Nervous System Neoplasms / Q000175:diagnosis* / Q000556:secondary* / Q000628:therapy; D002555:Cerebrospinal Fluid / Q000166:cytology; D016208:Databases, Factual; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D008279:Magnetic Resonance Imaging; D008875:Middle Aged; D009101:Multiple Myeloma / Q000175:diagnosis* / Q000473:pathology* / Q000628:therapy; D009367:Neoplasm Staging; D010950:Plasma Cells / Q000378:metabolism / Q000473:pathology; D012008:Recurrence; D012189:Retrospective Studies; D014182:Transplantation, Autologous; D016896:Treatment Outcome
keywords: Central nervous system; Intrathecal chemotherapy; Myeloma; Plasma cell leukemia; Transplant