Abstract
Fludarabine (FDR) therapy gives a response rate of about 30% in previously treated patients with Waldenström's macroglobulinemia (WM). The combination of FDR and cyclophosphamide (Cy) has been shown to be effective in chronic lymphoproliferative disorders. We administered the combination of FDR (30 mg/m2 i.v. D1–D3) and Cy (300 mg/m2 i.v. D1–D3) to 49 patients. Median age was 64 years. The median hemoglobin, albumin, beta 2 microglobulin and immunoglobulin M (IgM) levels were 9.9 g/100 ml, 39.6 g/l, 3 mg/l and 24.7 g/l, respectively. In all, 14 patients (29%) had not previously been treated. FDR/Cy was administered every 4 weeks for a median of four cycles. In all, 38 patients (77.6%) had partial responses, nine had stable disease and two had progressive disease. After a median of follow-up of 25 months, six patients relapsed and two patients developed large-cell lymphoma. The median time to treatment failure was 27 months. The main toxicity was hematological. In all, 12 patients died, four from progression, one from large-cell lymphoma, three from infection and four from a second malignancy. Two factors negatively influenced overall and event-free survival, age >65 years and IgM <40 g/l. The FDR/Cy combination, therefore, gives a high response rate in WM, even in previously treated patients with factors of poor prognosis.
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Dimopoulos MA, Panayiotidis P, Moulopoulos LA, Sfikakis P, Dalakas M . Waldenström's macroglobulinemia: clinical features, complications and management. J Clin Oncol 2000; 18: 41–49.
Kyle RA, Greipp PR, Gertz MA, Witzig TE, Lust JA, Lacy MQ et al. Waldenström's macroglobulinemia: a prospective study comparing daily with intermittent oral chlorambucil. Br J Haematol 2000; 108: 737–742.
Leblond V, Ben-Othman T, Deconinck E, Taksin AL, Harousseau JL, Delgado MA et al. Activity of fludarabine in previously treated Waldenström's macroglobulinemia: a report of 71 cases. J Clin Oncol 1998; 16: 2060–2064.
Leblond V, Choquet S . Fludarabine in Waldenström's macroglobulinemia. Semin Oncol 2003; 30: 239–242.
Dhodapkar MV, Jacobson JL, Gertz MA, Rivkin SE, Roodman GD, Tuscano JM et al. Prognostic factors and response to fludarabine therapy in patients with Waldenström macroglobulinemia: results of United States intergroup trial (South West Oncology Group S9003). Blood 2001; 98: 41–48.
Flinn IW, Byrd JC, Morrison C, Jamison J, Diehl LF, Murphy T et al. Fludarabine and cyclophosphamide with filgrastim support in patients with previously untreated indolent malignancy. Blood 2000; 96: 71–75.
Hallek M, Schmitt B, Wilhelm M, Busch R, Krober A, Fostitsch HP, et al, German Chronic Lymphocytic Leukaemia Study Group. Fludarabine plus cyclophosphamide is an efficient treatment for advanced chronic lymphocytic leukaemia (CLL): results of a phase II study of the German CLL Study Group. Br J Haematol 2001; 114: 342–348.
Schiavone EM, De Simone M, Palmieri S, Annunziata M, Pocali B, Copia C et al. Fludarabine plus cyclophosphamide for the treatment of advanced chronic lymphocytic leukemia. Eur J Haematol 2003; 7: 23–28.
Eichhorst B, Busch R, Hopfinger G . Fludarabine plus cyclophosphamide induces higher responses rate and longer progression free survival (PFS) than fludarabine alone in first line advanced chronic lymphocytic leukemia: results of a phase III study (CLL4 protocol) of the German CLL study group (GCLLSG). Blood 2003; 102: 72a 243 (abstract).
Owen RG, Treon SP, Al-Katib A, Fonseca R, Greipp PR, McMaster ML et al. Clinicopathological definition of Waldenström's macroglobulinemia: consensus panel recommendations from the Second International Workshop on Waldenström's Macroglobulinemia. Semin Oncol 2003; 30: 110–115.
Weber D, Treon SP, Emmanouilides C, Branagan AR, Byrd JC, Blade J et al. Uniform response criteria in Waldenström's macroglobulinemia: consensus recommendations from the Second International Workshop on Waldenström's Macroglobulinemia. Semin Oncol 2003; 30: 127–131.
Kaplan AL, Meier P . On parametric estimation from incomplete observations. J Am Stat Assoc 1958; 54: 457–481.
Cox DR . Regression models and life tables. JR Stat Soc B 1972; 74: 187–220.
Leblond V, Levy V, Maloisel F, Cazin B, Fermand JP, Harousseau JL et al. French Cooperative Group on Chronic Lymphocytic Leukemia and Macroglobulinemia. Multicenter, randomized comparative trial of fludarabine and the combination of cyclophosphamide-doxorubicin-prednisone in 92 patients with Waldenström macroglobulinemia in first relapse or with primary refractory disease. Blood 2001; 98: 2640–2644.
Levy V, Porcher R, Leblond V, Fermand JP, Cazin B, Maloisel F et al. French Cooperative Group on CLL and Macroglobulinemia. Evaluating treatment strategies in advanced Waldenström macroglobulinemia: use of quality-adjusted survival analysis. Leukemia 2001; 15: 1466–1470.
Plunkett W, Gandhi V, Huang P, Robertson LE, Yang LY, Gregoire V et al. Fludarabine: pharmacokinetics, mechanisms of action, and rationales for combination therapies. Semin Oncol 1993; 20 (Suppl 7): 2–12.
Yang LY, Li L, Keating MJ, Plunkett W . Arabinosyl-2-fluoroadenine augments cisplatin cytotoxicity and inhibits cisplatin-DNA cross-link repair. Mol Pharmacol 1995; 47: 1072–1079.
Dimopoulos MA, Hamilos G, Efstathiou E, Siapkaras I, Matsouka C, Gika D et al. Treatment of Waldenström's macroglobulinemia with the combination of fludarabine and cyclophosphamide. Leuk Lymphoma 2003; 44: 993–996.
Cheson BD . Infections and immunosuppressive complications of purine analog therapy. J Clin Oncol 1995; 13: 2431–2448.
Dimopoulos MA, Hamilos G, Zervas K, Symeonidis A, Kouvatseas G, Roussou P et al. Greek Myeloma Study Group. Survival and prognostic factors after initiation of treatment in Waldenström's macroglobulinemia. Ann Oncol 2003; 14: 1299–1305.
Garcia-Sanz R, Montoto S, Torrequebrada A, de Coca AG, Petit J, Sureda A et al. Spanish Group for the Study of Waldenström Macroglobulinaemia and PETHEMA (Programme for the Study and Treatment of Haematological Malignancies). Waldenström's Macroglobulinaemia: presenting features and outcome in a series with 217 cases. Br J Haematol 2001; 115: 575–582.
Morel P, Monconduit M, Jacomy D, Lenain P, Grosbois B, Bateli C et al. Prognostic factors in Waldenström macroglobulinemia: a report on 232 patients with the description of a new scoring system and its validation on 253 other patients. Blood 2000; 96: 852–858.
Gobbi PG, Bettini R, Montecucco C, Cavanna L, Morandi S, Pieresca C et al. Study of prognosis in Waldenström's macroglobulinemia: a proposal for a simple binary classification with clinical and investigational utility. Blood 1994; 83: 2939–2945.
Merlini G, Baldini L, Broglia C, Comelli M, Goldaniga M, Palladini G et al. Prognostic factors in symptomatic Waldenström's macroglobulinemia. Semin Oncol 2003; 30: 211–215.
Facon T, Brouillard M, Duhamel A, Morel P, Simon M, Jouet JP et al. Prognostic factors in Waldenström's macroglobulinemia: a report of 167 cases. J Clin Oncol 1993; 11: 1553–1558.
Dhodapkar MV, Jacobson JL, Gertz MA, Crowley JJ, Barlogie B . Prognostic factors and response to fludarabine therapy in Waldenström's macroglobulinemia: an update of a US intergroup trial. Semin Oncol 2003; 30: 220–225.
Tournilhac O, Leblond V, Tabrizi R, Gressin R, Senecal D, Milpied N et al. Transplantation in Waldenström's macroglobulinemia-the French experience. Semin Oncol 2003; 30: 291–296.
Tournilhac O, Cazin B, Lepretre S, Divine M, Maloum K, Delmer A et al. Impact of frontline fludarabine and cyclophophamide combined treatment on peripheral blood stem cell mobilization in B-cell chronic lymphocytic leukemia. Blood 2004; 103: 363–365.
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Tamburini, J., Lévy, V., Chaleteix, C. et al. Fludarabine plus cyclophosphamide in Waldenström's macroglobulinemia: results in 49 patients. Leukemia 19, 1831–1834 (2005). https://doi.org/10.1038/sj.leu.2403885
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DOI: https://doi.org/10.1038/sj.leu.2403885
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