BACKGROUND: Therapy for patients with Richter syndrome (RS) or fludarabine-refractory chronic lymphocytic leukemia (CLL) is unsatisfactory. A Phase II study was conducted to evaluate an alternating combination cytotoxic regimen given with rituximab and granulocyte-macrophage-colony stimulating factor (GM-CSF) in these patients. METHODS: Fludarabine-refractory CLL was defined as failure to respond to most recent prior fludarabine-containing regimen. Patients received up to six cycles of fractionated cyclophosphamide, vincristine, liposomal daunorubicin, and dexamethasone (hyper-CVXD) plus rituximab and GM-CSF alternating with methotrexate and cytarabine plus rituximab and GM-CSF. Response, toxicity, and survival data were compared with data from prior therapy with hyper-CVXD alone in this patient group. RESULTS: Forty-nine patients with RS (n = 30 patients) or refractory CLL (n = 19 patients) were treated on study. Nine patients (18%) achieved a complete remission, and 11 patients achieved a partial remission (22%), for an overall objective response (OR) rate of 41%. With a median follow-up of 7.5 months and a maximum follow-up of 15.2 months, the 12-month failure free survival (FFS) rate was 27%, and the overall survival (OS) rate was 39%. Nine patients (18%) died during the first cycle of therapy, and two patients (4%) died during the second cycle. There were no significant differences between the rates of OR, OS, and FFS in the current study and those obtained with hyper-CVXD alone on a prior study. CONCLUSIONS: The study regimen had activity and significant toxicity in patients with RS or fludarabine-refractory CLL. It was not clearly better compared with hyper-CVXD alone in this patient population. Copyright 2003 American Cancer Society.DOI 10.1002/cncr.11238
BACKGROUND: Therapy for patients with Richter syndrome (RS) or fludarabine-refractory chronic lymphocytic leukemia (CLL) is unsatisfactory. A Phase II study was conducted to evaluate an alternating combination cytotoxic regimen given with rituximab and granulocyte-macrophage-colony stimulating factor (GM-CSF) in these patients. METHODS:Fludarabine-refractory CLL was defined as failure to respond to most recent prior fludarabine-containing regimen. Patients received up to six cycles of fractionated cyclophosphamide, vincristine, liposomal daunorubicin, and dexamethasone (hyper-CVXD) plus rituximab and GM-CSF alternating with methotrexate and cytarabine plus rituximab and GM-CSF. Response, toxicity, and survival data were compared with data from prior therapy with hyper-CVXD alone in this patient group. RESULTS: Forty-nine patients with RS (n = 30 patients) or refractory CLL (n = 19 patients) were treated on study. Nine patients (18%) achieved a complete remission, and 11 patients achieved a partial remission (22%), for an overall objective response (OR) rate of 41%. With a median follow-up of 7.5 months and a maximum follow-up of 15.2 months, the 12-month failure free survival (FFS) rate was 27%, and the overall survival (OS) rate was 39%. Nine patients (18%) died during the first cycle of therapy, and two patients (4%) died during the second cycle. There were no significant differences between the rates of OR, OS, and FFS in the current study and those obtained with hyper-CVXD alone on a prior study. CONCLUSIONS: The study regimen had activity and significant toxicity in patients with RS or fludarabine-refractory CLL. It was not clearly better compared with hyper-CVXD alone in this patient population. Copyright 2003 American Cancer Society.DOI 10.1002/cncr.11238
Authors: Lorenzo Falchi; Michael J Keating; Edith M Marom; Mylene T Truong; Ellen J Schlette; Rachel L Sargent; Long Trinh; Xuemei Wang; Susan C Smith; Nitin Jain; Zeev Estrov; Susan O'Brien; William G Wierda; Susan Lerner; Alessandra Ferrajoli Journal: Blood Date: 2014-03-10 Impact factor: 22.113
Authors: Andrew D Zelenetz; Leo I Gordon; William G Wierda; Jeremy S Abramson; Ranjana H Advani; C Babis Andreadis; Nancy Bartlett; John C Byrd; Myron S Czuczman; Luis E Fayad; Richard I Fisher; Martha J Glenn; Thomas M Habermann; Nancy Lee Harris; Richard T Hoppe; Steven M Horwitz; Christopher R Kelsey; Youn H Kim; Susan Krivacic; Ann S LaCasce; Auayporn Nademanee; Pierluigi Porcu; Oliver Press; Rachel Rabinovitch; Nishitha Reddy; Erin Reid; Ayman A Saad; Lubomir Sokol; Lode J Swinnen; Christina Tsien; Julie M Vose; Lynn Wilson; Joachim Yahalom; Nadeem Zafar; Mary Dwyer; Hema Sundar Journal: J Natl Compr Canc Netw Date: 2015-03 Impact factor: 11.908
Authors: Apostolia M Tsimberidou; William G Wierda; Sijin Wen; William Plunkett; Susan O'Brien; Thomas J Kipps; Jeffrey A Jones; Xavier Badoux; Hagop Kantarjian; Michael J Keating Journal: Clin Lymphoma Myeloma Leuk Date: 2013-06-27