title: Intravenous methotrexate as central nervous system (CNS) prophylaxis is associated with a low risk of CNS recurrence in high-risk patients with diffuse large B-cell lymphoma.
abstract: BACKGROUND
  The outcome of patients with systemic diffuse large B-cell lymphoma (DLBCL) had improved over the past decade with the addition of monoclonal antibody therapy. Unfortunately, approximately 5% of these patients still developed a secondary central nervous system (CNS) recurrence followed invariably by rapid death. This rate is substantially increased in patients with certain high-risk features. Although prophylaxis against CNS recurrence with either intrathecal or intravenous methotrexate is commonly used for such patients, to the authors' knowledge, there is no standard of care. Retrospectively evaluated was the role of high-dose systemic methotrexate combined with standard cyclophosphamide, doxorubicin, vincristine, and prednisone with rituximab (R-CHOP) chemotherapy to decrease CNS recurrence in high-risk patients.
  
  
  METHODS
  A total of 65 patients with DLBCL and CNS risk factors were identified at the study institution between 2000 and 2008 who received intravenous methotrexate as CNS prophylaxis concurrent with standard systemic therapy with curative intent. CNS recurrence rate, progression-free survival, and overall survival were calculated.
  
  
  RESULTS
  Patients received a median of 3 cycles of methotrexate at a dose of 3.5 gm/m(2) with leucovorin rescue. The complete response rate was 86%, with 6% partial responses. At a median follow-up of 33 months, there were only 2 CNS recurrences (3%) in this high-risk population. The 3-year progression-free and overall survival rates were 76% and 78%, respectively. Complications associated with methotrexate therapy included transient renal dysfunction in 7 patients and a delay in systemic chemotherapy in 8 patients.
  
  
  CONCLUSIONS
  Intravenous methotrexate can be safely administered concurrently with R-CHOP and is associated with a low risk of CNS recurrence in high-risk patients.
authors.affiliation: Cancer Center, Massachusetts General Hospital, Boston, Massachusetts 02114, USA. jabramson@partners.org
authors.forename: Jeremy S
authors.initials: JS
authors.lastname: Abramson
authors.forename: Matthew
authors.initials: M
authors.lastname: Hellmann
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Barnes
authors.forename: Peter
authors.initials: P
authors.lastname: Hammerman
authors.forename: Christiana
authors.initials: C
authors.lastname: Toomey
authors.forename: Tak
authors.initials: T
authors.lastname: Takvorian
authors.forename: Alona
authors.initials: A
authors.lastname: Muzikansky
authors.forename: Ephraim P
authors.initials: EP
authors.lastname: Hochberg
mesh_terms: D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D058846:Antibodies, Monoclonal, Murine-Derived; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000032:analysis / Q000627:therapeutic use; D016543:Central Nervous System Neoplasms / Q000188:drug therapy / Q000517:prevention & control* / Q000556:secondary*; D003520:Cyclophosphamide / Q000032:analysis / Q000627:therapeutic use; D018572:Disease-Free Survival; D004317:Doxorubicin / Q000032:analysis / Q000627:therapeutic use; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007275:Injections, Intravenous; D016403:Lymphoma, Large B-Cell, Diffuse / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage* / Q000009:adverse effects; D008875:Middle Aged; D011241:Prednisone / Q000032:analysis / Q000627:therapeutic use; D012008:Recurrence; D012306:Risk; D000069283:Rituximab; D014750:Vincristine / Q000032:analysis / Q000627:therapeutic use
chemical_list: D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D000069283:Rituximab; D014750:Vincristine; D004317:Doxorubicin; D003520:Cyclophosphamide; D011241:Prednisone; D008727:Methotrexate