Fludarabine, Cyclophosphamide and Rituximab: an Effective Chemoimmunotherapy Combination with High Remission Rates for Chronic Lymphocytic Leukaemia

Overview

Journal Ir J Med Sci

Specialty General Medicine

Date 2009 Jun 5

PMID 19495836

Citations 1

Authors

A Hayat

S McGuckin

E Conneally

P V Brown

S R McCann

M Lawler

F Quinn

E Delaney

P ORourke

S Liptrot

D OBrien

E Vandenberghe

Affiliations

Soon will be listed here.

Abstract

Background: Combined Fludarabine and Cyclophosphamide is now standard first-line therapy in chronic lymphocytic leukaemia (CLL) and the addition of Rituximab improves outcome.

Methods: We adopted a modified Fludarabine, Cyclophosphamide and Rituximab (FCR) protocol in treating 39 patients (median age 57 years) with progressive or advanced CLL. Depending on CR, treatment was given for four or six cycles.

Result: Twenty-six patients were treatment naïve and 13 were pre-treated. Twelve patients had progressive Binet stage A, 16 stage B and 11 stage C disease. The overall response rate (ORR) was 100%, with 75% achieving CR. Neutropenia was the major toxicity in 71/187 (38%) of the cycles. There were five deaths, two from infection and three from progressive disease. Twenty-six of 31 patients have maintained their post-treatment disease status for a median of 17 months (2-41).

Conclusion: We conclude that FCR is a feasible, well-tolerated and effective treatment for patients with CLL.

Citing Articles

Dequalinium induces apoptosis in peripheral blood mononuclear cells isolated from human chronic lymphocytic leukemia.

Pajuelo L, Calvino E, Diez J, Boyano-Adanez M, Gil J, Sancho P Invest New Drugs. 2010; 29(6):1156-63.

PMID: 20524037 DOI: 10.1007/s10637-010-9454-y.

References

Flinn I, Byrd J, Morrison C, Jamison J, Diehl L, Murphy T . Fludarabine and cyclophosphamide with filgrastim support in patients with previously untreated indolent lymphoid malignancies. Blood. 2000; 96(1):71-5. View

Voena C, Ladetto M, Astolfi M, Provan D, Gribben J, Boccadoro M . A novel nested-PCR strategy for the detection of rearranged immunoglobulin heavy-chain genes in B cell tumors. Leukemia. 1997; 11(10):1793-8. DOI: 10.1038/sj.leu.2400801. View

van Dongen J, Langerak A, Bruggemann M, Evans P, Hummel M, Lavender F . Design and standardization of PCR primers and protocols for detection of clonal immunoglobulin and T-cell receptor gene recombinations in suspect lymphoproliferations: report of the BIOMED-2 Concerted Action BMH4-CT98-3936. Leukemia. 2003; 17(12):2257-317. DOI: 10.1038/sj.leu.2403202. View

Keating M, OBrien S, Kantarjian H, Plunkett W, Estey E, Koller C . Long-term follow-up of patients with chronic lymphocytic leukemia treated with fludarabine as a single agent. Blood. 1993; 81(11):2878-84. View

Manshouri T, Do K, Wang X, Giles F, OBrien S, Saffer H . Circulating CD20 is detectable in the plasma of patients with chronic lymphocytic leukemia and is of prognostic significance. Blood. 2002; 101(7):2507-13. DOI: 10.1182/blood-2002-06-1639. View

Hayat A, OBrien D, ORourke P, McGuckin S, Fitzgerald T, Conneally E . CD38 expression level and pattern of expression remains a reliable and robust marker of progressive disease in chronic lymphocytic leukemia. Leuk Lymphoma. 2006; 47(11):2371-9. DOI: 10.1080/10428190600947727. View

Winkler U, Jensen M, Manzke O, Schulz H, Diehl V, Engert A . Cytokine-release syndrome in patients with B-cell chronic lymphocytic leukemia and high lymphocyte counts after treatment with an anti-CD20 monoclonal antibody (rituximab, IDEC-C2B8). Blood. 1999; 94(7):2217-24. View

Di Gaetano N, Xiao Y, Erba E, Bassan R, Rambaldi A, Golay J . Synergism between fludarabine and rituximab revealed in a follicular lymphoma cell line resistant to the cytotoxic activity of either drug alone. Br J Haematol. 2001; 114(4):800-9. DOI: 10.1046/j.1365-2141.2001.03014.x. View

Foran J, Rohatiner A, Cunningham D, Popescu R, Solal-Celigny P, Ghielmini M . European phase II study of rituximab (chimeric anti-CD20 monoclonal antibody) for patients with newly diagnosed mantle-cell lymphoma and previously treated mantle-cell lymphoma, immunocytoma, and small B-cell lymphocytic lymphoma. J Clin Oncol. 2000; 18(2):317-24. DOI: 10.1200/JCO.2000.18.2.317. View

10.

Almasri N, Duque R, Iturraspe J, Everett E, Braylan R . Reduced expression of CD20 antigen as a characteristic marker for chronic lymphocytic leukemia. Am J Hematol. 1992; 40(4):259-63. DOI: 10.1002/ajh.2830400404. View

11.

OBrien S, Kantarjian H, Thomas D, Giles F, Freireich E, Cortes J . Rituximab dose-escalation trial in chronic lymphocytic leukemia. J Clin Oncol. 2001; 19(8):2165-70. DOI: 10.1200/JCO.2001.19.8.2165. View

12.

Nguyen D, Amess J, Doughty H, Hendry L, Diamond L . IDEC-C2B8 anti-CD20 (rituximab) immunotherapy in patients with low-grade non-Hodgkin's lymphoma and lymphoproliferative disorders: evaluation of response on 48 patients. Eur J Haematol. 1999; 62(2):76-82. DOI: 10.1111/j.1600-0609.1999.tb01725.x. View

13.

Keating M, OBrien S, Lerner S, Koller C, Beran M, Robertson L . Long-term follow-up of patients with chronic lymphocytic leukemia (CLL) receiving fludarabine regimens as initial therapy. Blood. 1998; 92(4):1165-71. View

14.

Clavio M, Miglino M, Spriano M, Pietrasanta D, Vallebella E, Celesti L . First line Fludarabine treatment of symptomatic chronic lymphoproliferative diseases: clinical results and molecular analysis of minimal residual disease. Eur J Haematol. 1998; 61(3):197-203. DOI: 10.1111/j.1600-0609.1998.tb01084.x. View

15.

Thornton P, Bellas C, Santon A, Shah G, Pocock C, Wotherspoon A . Richter's transformation of chronic lymphocytic leukemia. The possible role of fludarabine and the Epstein-Barr virus in its pathogenesis. Leuk Res. 2005; 29(4):389-95. DOI: 10.1016/j.leukres.2004.09.008. View

16.

Keating M, Chiorazzi N, Messmer B, Damle R, Allen S, Rai K . Biology and treatment of chronic lymphocytic leukemia. Hematology Am Soc Hematol Educ Program. 2003; :153-75. DOI: 10.1182/asheducation-2003.1.153. View

17.

Binet J, Auquier A, Dighiero G, Chastang C, PIGUET H, Goasguen J . A new prognostic classification of chronic lymphocytic leukemia derived from a multivariate survival analysis. Cancer. 1981; 48(1):198-206. DOI: 10.1002/1097-0142(19810701)48:1<198::aid-cncr2820480131>3.0.co;2-v. View

18.

Byrd J, Waselenko J, Maneatis T, Murphy T, Ward F, Monahan B . Rituximab therapy in hematologic malignancy patients with circulating blood tumor cells: association with increased infusion-related side effects and rapid blood tumor clearance. J Clin Oncol. 1999; 17(3):791-5. DOI: 10.1200/JCO.1999.17.3.791. View

19.

Keating M, OBrien S, Albitar M, Lerner S, Plunkett W, Giles F . Early results of a chemoimmunotherapy regimen of fludarabine, cyclophosphamide, and rituximab as initial therapy for chronic lymphocytic leukemia. J Clin Oncol. 2005; 23(18):4079-88. DOI: 10.1200/JCO.2005.12.051. View

20.

Rawstron A, Kennedy B, Evans P, Davies F, Richards S, Haynes A . Quantitation of minimal disease levels in chronic lymphocytic leukemia using a sensitive flow cytometric assay improves the prediction of outcome and can be used to optimize therapy. Blood. 2001; 98(1):29-35. DOI: 10.1182/blood.v98.1.29. View