title: Central nervous system involvement with multiple myeloma: long term survival can be achieved with radiation, intrathecal chemotherapy, and immunomodulatory agents.
abstract: Involvement of the central nervous system (CNS) in multiple myeloma (MM) is a rare complication, with reported survival of <6 months. This report describes 37 MM patients with leptomeningeal and/or parenchymal brain involvement treated at our institution and identifies factors associated with long-term survival. From January 1999 to December 2010, 37 patients with CNS MM were evaluated at our institution. Clinical characteristics, treatment and survival were retrospectively collected. CNS disease was present at MM diagnosis in 24% and at relapse in 76%. Plasma cell leukemia (40%) and skull plasmacytomas (65%) were common, suggesting haematological and contiguous spread. Intrathecal (IT) chemotherapy was used in 81%, cranial and/or spinal irradiation in 78%, and various systemic therapies [immunomodulatory agents (IMiDs) (51%), cisplatin-based (DPACE; cisplatin, doxorubicin, cyclophosphamide, etoposide) (27%), bortezomib (19%), alkylators (11%), dexamethasone alone (8%), auto-transplant (5%)]. Median survival from CNS disease was only 4·6 months [95% confidence interval (CI): 2·8-6·7]; however, nine patients had prolonged survival (median: 17·1 months, 95% CI: 13·2-67·4). In general, these long-term survivors were treated with radiotherapy, multi-dosing IT chemotherapy, and IMiD-containing therapy. CNS MM is a highly aggressive disease but in our experience, long-term survival can be achieved with the combination of multi-dosing IT chemotherapy, radiation and IMiD-based therapy.
authors.affiliation: Department of Medical Oncology and Haematology, Princess Margaret Cancer Centre, Toronto, ON, Canada. christine.chen@uhn.ca
authors.forename: Christine I
authors.initials: CI
authors.lastname: Chen
authors.forename: Esther
authors.initials: E
authors.lastname: Masih-Khan
authors.forename: Haiyan
authors.initials: H
authors.lastname: Jiang
authors.forename: Ahmed
authors.initials: A
authors.lastname: Rabea
authors.forename: Christine
authors.initials: C
authors.lastname: Cserti-Gazdewich
authors.forename: Victor H
authors.initials: VH
authors.lastname: Jimenez-Zepeda
authors.forename: Chia-Min
authors.initials: CM
authors.lastname: Chu
authors.forename: Vishal
authors.initials: V
authors.lastname: Kukreti
authors.forename: Suzanne
authors.initials: S
authors.lastname: Trudel
authors.forename: Rodger
authors.initials: R
authors.lastname: Tiedemann
authors.forename: Richard
authors.initials: R
authors.lastname: Tsang
authors.forename: Donna E
authors.initials: DE
authors.lastname: Reece
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use*; D001897:Boronic Acids / Q000008:administration & dosage; D000069286:Bortezomib; D002490:Central Nervous System / Q000473:pathology*; D002945:Cisplatin / Q000008:administration & dosage; D003131:Combined Modality Therapy; D016371:Cranial Irradiation; D003520:Cyclophosphamide / Q000008:administration & dosage; D003907:Dexamethasone / Q000627:therapeutic use; D018572:Disease-Free Survival; D004317:Doxorubicin / Q000008:administration & dosage / Q000627:therapeutic use; D005047:Etoposide / Q000008:administration & dosage; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007155:Immunologic Factors / Q000008:administration & dosage / Q000627:therapeutic use*; D007278:Injections, Spinal; D053208:Kaplan-Meier Estimate; D000077269:Lenalidomide; D008297:Male; D008578:Meninges / Q000473:pathology; D008875:Middle Aged; D009101:Multiple Myeloma / Q000188:drug therapy / Q000401:mortality / Q000473:pathology* / Q000532:radiotherapy / Q000601:surgery; D009915:Orbit / Q000473:pathology; D016016:Proportional Hazards Models; D011719:Pyrazines / Q000008:administration & dosage; D018714:Radiotherapy, Adjuvant; D012189:Retrospective Studies; D016879:Salvage Therapy; D013131:Spine / Q000473:pathology; D013792:Thalidomide / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000627:therapeutic use; D014182:Transplantation, Autologous; D016896:Treatment Outcome; D014750:Vincristine / Q000627:therapeutic use
chemical_list: D001897:Boronic Acids; D007155:Immunologic Factors; D011719:Pyrazines; D013792:Thalidomide; D014750:Vincristine; D000069286:Bortezomib; D005047:Etoposide; D003907:Dexamethasone; D004317:Doxorubicin; D003520:Cyclophosphamide; D000077269:Lenalidomide; D002945:Cisplatin
keywords: central nervous system; immunomodulatory drugs; intrathecal chemotherapy; leptomeningeal; multiple myeloma