title: Risk-tailored CNS prophylaxis in a mono-institutional series of 200 patients with diffuse large B-cell lymphoma treated in the rituximab era.
abstract: The most effective strategy to prevent central nervous system (CNS) dissemination in diffuse large B-cell lymphoma (DLBCL) remains an important, unmet clinical need. Herein, we report a retrospective analysis of risk-tailored CNS prophylaxis in 200 human immunodeficiency virus-negative adults with DLBCL treated with rituximab-CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) or similar. High risk of CNS relapse was defined by involvement of specific extranodal organs, or simultaneous presence of advanced stage and high serum lactate dehydrogenase level; CNS prophylaxis with high-dose methotrexate ± intrathecal chemotherapy (IT) was routinely used in high-risk patients diagnosed after 2007. CNS relapse risk was low in 93 patients and high in 107; 40 high-risk patients received prophylaxis, which consisted of IT alone in 7. At a median follow-up of 60 months, one low-risk and nine high-risk patients (1% vs. 8%; P = 0·01) experienced CNS relapse. In the high-risk group, CNS relapses occurred in 8/67 (12%) patients who did not receive prophylaxis and in 1/40 (2·5%) patients who did; the latter occurred in a patient managed with IT alone. CNS relapse rate was 12% (9/74) for patients treated with "inadequate" prophylaxis (none or IT only) and 0% (0/33) for patients managed with intravenous prophylaxis (P = 0·03). In conclusion, high-dose methotrexate-based prophylaxis significantly reduces CNS failures in high-risk patients stratified by involvement of specific extranodal sites and International Prognostic Index.
authors.affiliation: Division of Onco-Haematological Medicine, Department of Onco-Haematology, Unit of Lymphoid Malignancies, Milan, Italy.
authors.forename: Andrés J M
authors.initials: AJ
authors.lastname: Ferreri
authors.forename: Marta
authors.initials: M
authors.lastname: Bruno-Ventre
authors.forename: Giovanni
authors.initials: G
authors.lastname: Donadoni
authors.forename: Maurilio
authors.initials: M
authors.lastname: Ponzoni
authors.forename: Giovanni
authors.initials: G
authors.lastname: Citterio
authors.forename: Marco
authors.initials: M
authors.lastname: Foppoli
authors.forename: Alessandro
authors.initials: A
authors.lastname: Vignati
authors.forename: Lydia
authors.initials: L
authors.lastname: Scarfò
authors.forename: Marianna
authors.initials: M
authors.lastname: Sassone
authors.forename: Silvia
authors.initials: S
authors.lastname: Govi
authors.forename: Federico
authors.initials: F
authors.lastname: Caligaris-Cappio
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D058846:Antibodies, Monoclonal, Murine-Derived / Q000008:administration & dosage*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D016543:Central Nervous System Neoplasms / Q000401:mortality / Q000517:prevention & control* / Q000556:secondary; D003520:Cyclophosphamide / Q000008:administration & dosage; D004317:Doxorubicin / Q000008:administration & dosage; D005260:Female; D006801:Humans; D016403:Lymphoma, Large B-Cell, Diffuse / Q000188:drug therapy* / Q000401:mortality; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage*; D008875:Middle Aged; D011241:Prednisone / Q000008:administration & dosage; D012008:Recurrence; D012189:Retrospective Studies; D012307:Risk Factors; D000069283:Rituximab; D014750:Vincristine / Q000008:administration & dosage
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; C571759:R-CHOP protocol; D000069283:Rituximab; D014750:Vincristine; D004317:Doxorubicin; D003520:Cyclophosphamide; D011241:Prednisone; D008727:Methotrexate
keywords: central nervous system prophylaxis; diffuse large B-cell lymphoma; intrathecal chemotherapy; liposomal cytarabine; methotrexate