Fractionated cyclophosphamide, vincristine, liposomal daunorubicin, and dexamethasone plus rituximab and granulocyte-macrophage-colony stimulating factor (GM-CSF) alternating with methotrexate and cytarabine plus rituximab and GM-CSF in patients with Richter syndrome or fludarabine-refractory chronic lymphocytic leukemia

Apostolia M. Tsimberidou, Hagop M. Kantarjian, Jorge Cortes, Deborah A. Thomas, Stefan Faderl, Guillermo Garcia-Manero, Srdan Verstovsek, Alessandra Ferrajoli, William Wierda, Yesid Alvarado, Susan M. O'Brien, Maher Albitar, Michael J. Keating, Francis J. Giles

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1711-1720
Number of pages10
JournalCancer
Volume97
Issue number7
DOIs
StatePublished - Apr 1 2003
Externally publishedYes

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Daunorubicin
Cytarabine
Vincristine
B-Cell Chronic Lymphocytic Leukemia
Granulocyte-Macrophage Colony-Stimulating Factor
Methotrexate
Cyclophosphamide
Dexamethasone
fludarabine
Rituximab
Survival
Survival Rate
Therapeutics

Keywords

  • Chronic lymphocytic leukemia
  • Prognosis
  • Richter syndrome
  • Therapy

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Fractionated cyclophosphamide, vincristine, liposomal daunorubicin, and dexamethasone plus rituximab and granulocyte-macrophage-colony stimulating factor (GM-CSF) alternating with methotrexate and cytarabine plus rituximab and GM-CSF in patients with Richter syndrome or fludarabine-refractory chronic lymphocytic leukemia. / Tsimberidou, Apostolia M.; Kantarjian, Hagop M.; Cortes, Jorge; Thomas, Deborah A.; Faderl, Stefan; Garcia-Manero, Guillermo; Verstovsek, Srdan; Ferrajoli, Alessandra; Wierda, William; Alvarado, Yesid; O'Brien, Susan M.; Albitar, Maher; Keating, Michael J.; Giles, Francis J.

In: Cancer, Vol. 97, No. 7, 01.04.2003, p. 1711-1720.

Research output: Contribution to journalArticle

Tsimberidou, Apostolia M. ; Kantarjian, Hagop M. ; Cortes, Jorge ; Thomas, Deborah A. ; Faderl, Stefan ; Garcia-Manero, Guillermo ; Verstovsek, Srdan ; Ferrajoli, Alessandra ; Wierda, William ; Alvarado, Yesid ; O'Brien, Susan M. ; Albitar, Maher ; Keating, Michael J. ; Giles, Francis J. / Fractionated cyclophosphamide, vincristine, liposomal daunorubicin, and dexamethasone plus rituximab and granulocyte-macrophage-colony stimulating factor (GM-CSF) alternating with methotrexate and cytarabine plus rituximab and GM-CSF in patients with Richter syndrome or fludarabine-refractory chronic lymphocytic leukemia. In: Cancer. 2003 ; Vol. 97, No. 7. pp. 1711-1720.
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title = "Fractionated cyclophosphamide, vincristine, liposomal daunorubicin, and dexamethasone plus rituximab and granulocyte-macrophage-colony stimulating factor (GM-CSF) alternating with methotrexate and cytarabine plus rituximab and GM-CSF in patients with Richter syndrome or fludarabine-refractory chronic lymphocytic leukemia",
abstract = "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.",
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TY - JOUR

T1 - Fractionated cyclophosphamide, vincristine, liposomal daunorubicin, and dexamethasone plus rituximab and granulocyte-macrophage-colony stimulating factor (GM-CSF) alternating with methotrexate and cytarabine plus rituximab and GM-CSF in patients with Richter syndrome or fludarabine-refractory chronic lymphocytic leukemia

AU - Tsimberidou, Apostolia M.

AU - Kantarjian, Hagop M.

AU - Cortes, Jorge

AU - Thomas, Deborah A.

AU - Faderl, Stefan

AU - Garcia-Manero, Guillermo

AU - Verstovsek, Srdan

AU - Ferrajoli, Alessandra

AU - Wierda, William

AU - Alvarado, Yesid

AU - O'Brien, Susan M.

AU - Albitar, Maher

AU - Keating, Michael J.

AU - Giles, Francis J.

PY - 2003/4/1

Y1 - 2003/4/1

N2 - 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.

AB - 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.

KW - Chronic lymphocytic leukemia

KW - Prognosis

KW - Richter syndrome

KW - Therapy

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DO - 10.1002/cncr.11238

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JF - Cancer

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