title: CNS events in elderly patients with aggressive lymphoma treated with modern chemotherapy (CHOP-14) with or without rituximab: an analysis of patients treated in the RICOVER-60 trial of the German High-Grade Non-Hodgkin Lymphoma Study Group (DSHNHL).
abstract: One thousand two hundred twenty-two patients treated in the Rituximab with CHOP over age 60 years (RICOVER-60) trial were examined for central nervous system (CNS) disease developing during first-line therapy or after a complete or partial remission had been achieved. Patients received 6 or 8 courses of CHOP (cyclophosphamide, adriamycin, vincristine, prednisone) administered every 2 weeks (CHOP-14) with or without rituximab. CNS prophylaxis for patients with involvement of bone marrow, testes, upper neck, or head consisted of intrathecal (i.th.) methotrexate (days 1 and 5 of first 2 courses). Fifty-eight cases of lymphoma in the CNS were observed (36/609 patients in the CHOP-14 and 22/608 patients in the arituximab-CHOP-14 [R-CHOP-14] arm). The estimated 2-year incidence of CNS disease was 6.9% (confidence interval [CI] 4.5; 9.3) after CHOP-14 and 4.1% (CI 2.3; 5.9) after R-CHOP-14. R-CHOP reduced the relative risk for CNS disease to 0.58 (95% CI 0.3; 1.0, P = .046). Cox regression analysis identified "involvement of more than 1 extranodal site" and "B-symptoms" as significant risk factors for CNS disease. Patients treated with R-CHOP-14 did not show any benefit from i.th. methotrexate. We conclude that elderly patients with aggressive CD20-positive lymphoma show a significantly lower incidence of CNS disease if treated with R-CHOP-14 instead of CHOP-14. Intrathecal methotrexate has no role in preventing CNS disease for patients treated with combined immunochemotherapy (R-CHOP-14)--with the possible exception of patients with testicular involvement.
authors.affiliation: Department of Hematology and Stem Cell Transplantation, Asklepios Hospital St Georg, Hamburg, Germany.
authors.forename: Volkmar
authors.initials: V
authors.lastname: Boehme
authors.forename: Norbert
authors.initials: N
authors.lastname: Schmitz
authors.forename: Samira
authors.initials: S
authors.lastname: Zeynalova
authors.forename: Markus
authors.initials: M
authors.lastname: Loeffler
authors.forename: Michael
authors.initials: M
authors.lastname: Pfreundschuh
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000009:adverse effects* / Q000276:immunology / Q000627:therapeutic use*; D058846:Antibodies, Monoclonal, Murine-Derived; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects* / Q000627:therapeutic use*; D002493:Central Nervous System Diseases / Q000139:chemically induced* / Q000517:prevention & control; D003131:Combined Modality Therapy; D003520:Cyclophosphamide / Q000009:adverse effects / Q000627:therapeutic use; D004317:Doxorubicin / Q000009:adverse effects / Q000627:therapeutic use; D005260:Female; D005858:Germany; D006801:Humans; D007167:Immunotherapy; D008228:Lymphoma, Non-Hodgkin / Q000188:drug therapy* / Q000276:immunology* / Q000473:pathology / Q000532:radiotherapy; D008297:Male; D008875:Middle Aged; D011241:Prednisone / Q000009:adverse effects / Q000627:therapeutic use; D012307:Risk Factors; D000069283:Rituximab; D014750:Vincristine / Q000009:adverse effects / Q000627:therapeutic use
chemical_list: D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D000069283:Rituximab; D014750:Vincristine; D004317:Doxorubicin; D003520:Cyclophosphamide; D011241:Prednisone