Fractionated cyclophosphamide, vincristine, liposomal daunorubicin (daunoxome), and dexamethasone (hyperCVXD) regimen in Richter's syndrome

B. S. Dabaja, S. M. O'Brien, H. M. Kantarjian, J. E. Cortes, D. A. Thomas, M. Albitar, E. S. Schlette, S. Faderl, A. Sarris, M. J. Keating, F. J. Giles

Research output: Contribution to journalArticle

Abstract

Approximately 3 to 5% of patients with chronic lymphocytic leukemia (CLL) develop an aggressive large cell non Hodgkin's lymphoma (NHL) known as Richter's syndrome (RS). RS has a poor prognosis and a response rate of <10% with fludarabine-based or other cytotoxic combination regimens. The aim of this study was to evaluate the efficacy and toxicity of the hyperCVXD regimen in RS. Twenty-nine patients, median age 61 years (36-75) 23 males, were treated. Prior diagnosis was CLL in 26 patients, NHL in 2, and Prolymphocytic leukemia in 1. Treatment consisted of fractionated cyclophosphamide, vincristine, daunoXome and dexamethasone. Six patients (20%) died while receiving study therapy, 4 (14%) during the first cycle of whom 2 had started therapy with overt pneumonia. Grade 4 granulocytopenia occurred in all 95 cycles of therapy with a median time to recovery of 14 days. Twenty three (24%) cycles were complicated by fever, and 15 (15%) by pneumonia. Sepsis was documented in 8 (8%) cycles, and neuropathy in 5 (5%) of cycles. Twenty three patients had a platelet count < 100 × 109/1 prior to therapy: a greater than 50% decrease in platelet count over pre-therapy level occurred in 79% of first cycles, overt bleeding occurred in 4 (4%) of all cycles. Eleven of 29 (38%) patients achieved complete remission (CR), 4 of whom have relapsed after 5, 6, 9, and 12 months of remission. Two of 11 CR patients presented with RS without any prior CLL therapy. One patient had a partial remission. Thus the overall response rate was 12/29 (41%). Overall median survival was 10 months, 19 months in patients who achieved CR, 3 months in those who did not (p=0.0008). A landmark analysis performed at 2 months from start of therapy comparing patients alive in CR versus patients alive but not in CR showed a median survival of 19 months versus 6 months, respectively (p0.0017). In conclusion the hyper CVXD regimen has a relatively high response rate, significant toxicity and a moderate impact on survival in RS.

Original languageEnglish (US)
Pages (from-to)329-337
Number of pages9
JournalLeukemia and Lymphoma
Volume42
Issue number3
DOIs
StatePublished - Jan 1 2001
Externally publishedYes

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Daunorubicin
Vincristine
Cyclophosphamide
Dexamethasone
B-Cell Chronic Lymphocytic Leukemia
Therapeutics
Platelet Count
Non-Hodgkin's Lymphoma
Survival
Pneumonia
Prolymphocytic Leukemia
Agranulocytosis
Sepsis
Fever
Hemorrhage

Keywords

  • CCL
  • Cyclophosphamide hyper CVXD
  • Liposomal daunorubicin
  • Richter's

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research

Cite this

Fractionated cyclophosphamide, vincristine, liposomal daunorubicin (daunoxome), and dexamethasone (hyperCVXD) regimen in Richter's syndrome. / Dabaja, B. S.; O'Brien, S. M.; Kantarjian, H. M.; Cortes, J. E.; Thomas, D. A.; Albitar, M.; Schlette, E. S.; Faderl, S.; Sarris, A.; Keating, M. J.; Giles, F. J.

In: Leukemia and Lymphoma, Vol. 42, No. 3, 01.01.2001, p. 329-337.

Research output: Contribution to journalArticle

Dabaja, BS, O'Brien, SM, Kantarjian, HM, Cortes, JE, Thomas, DA, Albitar, M, Schlette, ES, Faderl, S, Sarris, A, Keating, MJ & Giles, FJ 2001, 'Fractionated cyclophosphamide, vincristine, liposomal daunorubicin (daunoxome), and dexamethasone (hyperCVXD) regimen in Richter's syndrome', Leukemia and Lymphoma, vol. 42, no. 3, pp. 329-337. https://doi.org/10.3109/10428190109064589
Dabaja, B. S. ; O'Brien, S. M. ; Kantarjian, H. M. ; Cortes, J. E. ; Thomas, D. A. ; Albitar, M. ; Schlette, E. S. ; Faderl, S. ; Sarris, A. ; Keating, M. J. ; Giles, F. J. / Fractionated cyclophosphamide, vincristine, liposomal daunorubicin (daunoxome), and dexamethasone (hyperCVXD) regimen in Richter's syndrome. In: Leukemia and Lymphoma. 2001 ; Vol. 42, No. 3. pp. 329-337.
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abstract = "Approximately 3 to 5{\%} of patients with chronic lymphocytic leukemia (CLL) develop an aggressive large cell non Hodgkin's lymphoma (NHL) known as Richter's syndrome (RS). RS has a poor prognosis and a response rate of <10{\%} with fludarabine-based or other cytotoxic combination regimens. The aim of this study was to evaluate the efficacy and toxicity of the hyperCVXD regimen in RS. Twenty-nine patients, median age 61 years (36-75) 23 males, were treated. Prior diagnosis was CLL in 26 patients, NHL in 2, and Prolymphocytic leukemia in 1. Treatment consisted of fractionated cyclophosphamide, vincristine, daunoXome and dexamethasone. Six patients (20{\%}) died while receiving study therapy, 4 (14{\%}) during the first cycle of whom 2 had started therapy with overt pneumonia. Grade 4 granulocytopenia occurred in all 95 cycles of therapy with a median time to recovery of 14 days. Twenty three (24{\%}) cycles were complicated by fever, and 15 (15{\%}) by pneumonia. Sepsis was documented in 8 (8{\%}) cycles, and neuropathy in 5 (5{\%}) of cycles. Twenty three patients had a platelet count < 100 × 109/1 prior to therapy: a greater than 50{\%} decrease in platelet count over pre-therapy level occurred in 79{\%} of first cycles, overt bleeding occurred in 4 (4{\%}) of all cycles. Eleven of 29 (38{\%}) patients achieved complete remission (CR), 4 of whom have relapsed after 5, 6, 9, and 12 months of remission. Two of 11 CR patients presented with RS without any prior CLL therapy. One patient had a partial remission. Thus the overall response rate was 12/29 (41{\%}). Overall median survival was 10 months, 19 months in patients who achieved CR, 3 months in those who did not (p=0.0008). A landmark analysis performed at 2 months from start of therapy comparing patients alive in CR versus patients alive but not in CR showed a median survival of 19 months versus 6 months, respectively (p0.0017). In conclusion the hyper CVXD regimen has a relatively high response rate, significant toxicity and a moderate impact on survival in RS.",
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AU - Cortes, J. E.

AU - Thomas, D. A.

AU - Albitar, M.

AU - Schlette, E. S.

AU - Faderl, S.

AU - Sarris, A.

AU - Keating, M. J.

AU - Giles, F. J.

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N2 - Approximately 3 to 5% of patients with chronic lymphocytic leukemia (CLL) develop an aggressive large cell non Hodgkin's lymphoma (NHL) known as Richter's syndrome (RS). RS has a poor prognosis and a response rate of <10% with fludarabine-based or other cytotoxic combination regimens. The aim of this study was to evaluate the efficacy and toxicity of the hyperCVXD regimen in RS. Twenty-nine patients, median age 61 years (36-75) 23 males, were treated. Prior diagnosis was CLL in 26 patients, NHL in 2, and Prolymphocytic leukemia in 1. Treatment consisted of fractionated cyclophosphamide, vincristine, daunoXome and dexamethasone. Six patients (20%) died while receiving study therapy, 4 (14%) during the first cycle of whom 2 had started therapy with overt pneumonia. Grade 4 granulocytopenia occurred in all 95 cycles of therapy with a median time to recovery of 14 days. Twenty three (24%) cycles were complicated by fever, and 15 (15%) by pneumonia. Sepsis was documented in 8 (8%) cycles, and neuropathy in 5 (5%) of cycles. Twenty three patients had a platelet count < 100 × 109/1 prior to therapy: a greater than 50% decrease in platelet count over pre-therapy level occurred in 79% of first cycles, overt bleeding occurred in 4 (4%) of all cycles. Eleven of 29 (38%) patients achieved complete remission (CR), 4 of whom have relapsed after 5, 6, 9, and 12 months of remission. Two of 11 CR patients presented with RS without any prior CLL therapy. One patient had a partial remission. Thus the overall response rate was 12/29 (41%). Overall median survival was 10 months, 19 months in patients who achieved CR, 3 months in those who did not (p=0.0008). A landmark analysis performed at 2 months from start of therapy comparing patients alive in CR versus patients alive but not in CR showed a median survival of 19 months versus 6 months, respectively (p0.0017). In conclusion the hyper CVXD regimen has a relatively high response rate, significant toxicity and a moderate impact on survival in RS.

AB - Approximately 3 to 5% of patients with chronic lymphocytic leukemia (CLL) develop an aggressive large cell non Hodgkin's lymphoma (NHL) known as Richter's syndrome (RS). RS has a poor prognosis and a response rate of <10% with fludarabine-based or other cytotoxic combination regimens. The aim of this study was to evaluate the efficacy and toxicity of the hyperCVXD regimen in RS. Twenty-nine patients, median age 61 years (36-75) 23 males, were treated. Prior diagnosis was CLL in 26 patients, NHL in 2, and Prolymphocytic leukemia in 1. Treatment consisted of fractionated cyclophosphamide, vincristine, daunoXome and dexamethasone. Six patients (20%) died while receiving study therapy, 4 (14%) during the first cycle of whom 2 had started therapy with overt pneumonia. Grade 4 granulocytopenia occurred in all 95 cycles of therapy with a median time to recovery of 14 days. Twenty three (24%) cycles were complicated by fever, and 15 (15%) by pneumonia. Sepsis was documented in 8 (8%) cycles, and neuropathy in 5 (5%) of cycles. Twenty three patients had a platelet count < 100 × 109/1 prior to therapy: a greater than 50% decrease in platelet count over pre-therapy level occurred in 79% of first cycles, overt bleeding occurred in 4 (4%) of all cycles. Eleven of 29 (38%) patients achieved complete remission (CR), 4 of whom have relapsed after 5, 6, 9, and 12 months of remission. Two of 11 CR patients presented with RS without any prior CLL therapy. One patient had a partial remission. Thus the overall response rate was 12/29 (41%). Overall median survival was 10 months, 19 months in patients who achieved CR, 3 months in those who did not (p=0.0008). A landmark analysis performed at 2 months from start of therapy comparing patients alive in CR versus patients alive but not in CR showed a median survival of 19 months versus 6 months, respectively (p0.0017). In conclusion the hyper CVXD regimen has a relatively high response rate, significant toxicity and a moderate impact on survival in RS.

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