title: Central nervous system prophylaxis with intrathecal liposomal cytarabine in a subset of high-risk patients with diffuse large B-cell lymphoma receiving first line systemic therapy in a prospective trial.
abstract: The dissemination in the central nervous system (CNS) is an uncommon but fatal complication occurring in patients with diffuse large B-cell lymphoma (DLBCL). Standard prophylaxis has been demonstrated to reduce CNS relapse and improve survival rates. Intrathecal (IT) liposomal cytarabine allows maintaining elevated drug levels in the cerebrospinal fluid for an extended period of time. Data on the efficacy and safety of liposomal cytarabine as CNS prophylaxis in patients with DLBCL are still insufficient. The objective of the present study was to evaluate the effectiveness and safety of the prophylaxis with IT liposomal cytarabine in prevention of CNS relapse in high-risk patients with DLBCL who were included in a trial of first line systemic therapy with 6 cycles of dose-dense R-CHOP every 14 days. Twenty-four (18.6 %) out of 129 patients were identified to have risk factors for CNS involvement, defined as follows: >30 % bone marrow infiltration, testes infiltration, retroperitoneal mass ≥10 cm, Waldeyer ring, or bulky cervical nodes involvement. Liposomal cytarabine (50 mg) was administered by lumbar puncture the first day of the 1st, 2nd, and 6th cycle of R-CHOP14 scheme. Among 70 IT infusions, grade 3-4 adverse events reported were headache (one patient) and nausea/vomiting (one patient). With a median follow-up of 40.1 months, no CNS involvement by DLBCL was observed in any patient. In conclusion, IT liposomal cytarabine is safe, feasible, and effective for CNS prophylaxis, causing few associated risks and little discomfort to patients with DLBCL.
authors.affiliation: Institut Català d'Oncologia. IDIBELL., Hospital Duran i Reynals, Av. Gran Vía 199-203, 08908, L'Hospitalet de Llobregat, Barcelona, Spain. e.gonzalez@iconcologia.net.
authors.forename: E
authors.initials: E
authors.lastname: González-Barca
authors.affiliation: Hospital Universitario La Paz, Madrid, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Canales
authors.affiliation: Hospital del Mar, Barcelona, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Salar
authors.affiliation: Hospital Donostia, San Sebastián, Spain.
authors.forename: J J
authors.initials: JJ
authors.lastname: Ferreiro-Martínez
authors.affiliation: Hospital Dr. Peset, Valencia, Spain.
authors.forename: S
authors.initials: S
authors.lastname: Ferrer-Bordes
authors.affiliation: Hospital Puerta de Hierro, Madrid, Spain.
authors.forename: J A
authors.initials: JA
authors.lastname: García-Marco
authors.affiliation: Hospital Morales Meseguer, Murcia, Spain.
authors.forename: J J
authors.initials: JJ
authors.lastname: Sánchez-Blanco
authors.affiliation: Hospital Río Hortega, Valladolid, Spain.
authors.forename: J
authors.initials: J
authors.lastname: García-Frade
authors.affiliation: Fundación Hospital de Alcorcón, Madrid, Spain.
authors.forename: J
authors.initials: J
authors.lastname: Peñalver
authors.affiliation: Complexo Hospitalario de Santiago, Santiago de Compostela, Spain.
authors.forename: J L
authors.initials: JL
authors.lastname: Bello-López
authors.affiliation: Institut Català d'Oncologia - Hospital Germans Trias i Pujol, Badalona, Spain.
authors.forename: J M
authors.initials: JM
authors.lastname: Sancho
authors.affiliation: Hospital Clínico Universitario de Salamanca, Salamanca, Spain.
authors.forename: D
authors.initials: D
authors.lastname: Caballero
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D058846:Antibodies, Monoclonal, Murine-Derived / Q000008:administration & dosage; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D003520:Cyclophosphamide / Q000008:administration & dosage; D003561:Cytarabine / Q000008:administration & dosage*; D004317:Doxorubicin / Q000008:administration & dosage; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007278:Injections, Spinal; D016403:Lymphoma, Large B-Cell, Diffuse / Q000175:diagnosis* / Q000188:drug therapy* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D056990:Post-Exposure Prophylaxis / Q000379:methods; D011241:Prednisone / Q000008:administration & dosage; D011446:Prospective Studies; D012307:Risk Factors; D000069283:Rituximab; D015996:Survival Rate; D014750:Vincristine / Q000008:administration & dosage; D055815:Young Adult
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D000964:Antimetabolites, Antineoplastic; C571759:R-CHOP protocol; D003561:Cytarabine; D000069283:Rituximab; D014750:Vincristine; D004317:Doxorubicin; D003520:Cyclophosphamide; D011241:Prednisone
keywords: Central nervous system; Diffuse large B-cell lymphoma; Liposomal cytarabine; Prophylaxis