TY - JOUR
T1 - High doses of antimetabolites followed by high-dose sequential chemoimmunotherapy and autologous stem-cell transplantation in patients with systemic B-cell lymphoma and secondary CNS involvement
T2 - Final results of a multicenter phase II trial
AU - Ferreri, Andrés J M
AU - Donadoni, Giovanni
AU - Cabras, Maria Giuseppina
AU - Patti, Caterina
AU - Mian, Michael
AU - Zambello, Renato
AU - Tarella, Corrado
AU - Di Nicola, Massimo
AU - D'Arco, Alfonso M.
AU - Doa, Gianluca
AU - Bruno-Ventre, Marta
AU - Assanelli, Andrea
AU - Foppoli, Marco
AU - Citterio, Giovanni
AU - Fanni, Alessandro
AU - Mulè, Antonino
AU - Caligaris-Cappio, Federico
AU - Ciceri, Fabio
PY - 2015/11/20
Y1 - 2015/11/20
N2 - Purpose Treatment of secondary CNS dissemination in patients with aggressive lymphomas remains an mportant, unmet clinical need. Herein, we report the final results of a multicenter phase II tria addressing a new treatment for secondary CNS lymphoma based on encouraging experiences with high doses of antimetabolites in primary CNS lymphoma and with rituximab plus high-dose sequential chemoimmunotherapy (R-HDS) in relapsed aggressive lymphoma Patients and Methods HIV-negative patients with aggressive B-cell lymphoma and secondary CNS involvement at diagnosis or relapse, age 18 to 70 years, and Eastern Cooperative Oncology Group performance status ≥ 3 were enrolled and treated with high-doses of methotrexate and cytarabine, followed by R-HDS (cyclophosphamide, cytarabine, and etoposide) supported by autologous stem-cell transplantation (ASCT). Treatment included eight doses of rituximab and four doses of intratheca iposomal cytarabine. The primary end point was 2-year event-free survival; the planned accrua was 38 patients Results Thirty-eight patients were enrolled; CNS disease was detected at presentation in 16 patients. Toxicity was usually hematologic and manageable, with grade 4 febrile neutropenia in 3% of delivered courses and grade 4 nonhematologic toxicity in 2% of delivered courses. Four patients died because of toxicity. Autologous stem cells were successfully collected in 24 (89%) of 27 patients (median, 10 × 106/kg); 20 patients underwent ASCT. Complete response was achieved in 24 patients (complete response rate, 63%; 95% CI, 48% to 78%). At a median follow-up of 48 months, 17 patients remained relapse free, with a 2-year event-free survival rate of 50% ± 8%. At 5 years, 16 patients were alive, with a 5-year overall survival rate of 41% ± 8% for the whole series and 68% ±11% for patients who received transplantation. Systemic (extra-CNS) and/or meningeal disease did not affect outcome. Conclusion The combination of high doses of antimetabolites, R-HDS, and ASCT is feasible and effective in patients age 18 to 70 years old with secondary CNS lymphoma, and we propose it as a new standard therapeutic option.
AB - Purpose Treatment of secondary CNS dissemination in patients with aggressive lymphomas remains an mportant, unmet clinical need. Herein, we report the final results of a multicenter phase II tria addressing a new treatment for secondary CNS lymphoma based on encouraging experiences with high doses of antimetabolites in primary CNS lymphoma and with rituximab plus high-dose sequential chemoimmunotherapy (R-HDS) in relapsed aggressive lymphoma Patients and Methods HIV-negative patients with aggressive B-cell lymphoma and secondary CNS involvement at diagnosis or relapse, age 18 to 70 years, and Eastern Cooperative Oncology Group performance status ≥ 3 were enrolled and treated with high-doses of methotrexate and cytarabine, followed by R-HDS (cyclophosphamide, cytarabine, and etoposide) supported by autologous stem-cell transplantation (ASCT). Treatment included eight doses of rituximab and four doses of intratheca iposomal cytarabine. The primary end point was 2-year event-free survival; the planned accrua was 38 patients Results Thirty-eight patients were enrolled; CNS disease was detected at presentation in 16 patients. Toxicity was usually hematologic and manageable, with grade 4 febrile neutropenia in 3% of delivered courses and grade 4 nonhematologic toxicity in 2% of delivered courses. Four patients died because of toxicity. Autologous stem cells were successfully collected in 24 (89%) of 27 patients (median, 10 × 106/kg); 20 patients underwent ASCT. Complete response was achieved in 24 patients (complete response rate, 63%; 95% CI, 48% to 78%). At a median follow-up of 48 months, 17 patients remained relapse free, with a 2-year event-free survival rate of 50% ± 8%. At 5 years, 16 patients were alive, with a 5-year overall survival rate of 41% ± 8% for the whole series and 68% ±11% for patients who received transplantation. Systemic (extra-CNS) and/or meningeal disease did not affect outcome. Conclusion The combination of high doses of antimetabolites, R-HDS, and ASCT is feasible and effective in patients age 18 to 70 years old with secondary CNS lymphoma, and we propose it as a new standard therapeutic option.
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U2 - 10.1200/JCO.2015.61.1236
DO - 10.1200/JCO.2015.61.1236
M3 - Article
C2 - 26282634
AN - SCOPUS:84948458088
VL - 33
SP - 3903
EP - 3910
JO - Journal of Clinical Oncology
JF - Journal of Clinical Oncology
SN - 0732-183X
IS - 33
ER -