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Phase II fludarabine and cyclophosphamide for the treatment of indolent B cell non-follicular lymphomas: final results of the LL02 trialof the Gruppo Italiano per lo Studio dei Linfomi (GISL)

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Abstract

Indolent non-follicular non-Hodgkin lymphomas (INFL) are a heterogenous subset whose treatment has been poorly investigated. In this context we have evaluated the efficacy and safety of combined fludarabine and cyclophosphamide (FC) upfront therapy. Sixty-three patients with advanced INFL were enrolled in the study. Therapy consisted in FC combination (25 and 250 mg/m2, i.v., respectively, for three consecutive days) every 28 days for six courses. After histological review, 61 patients (36 men, median age 64 years, range 40–70 years) were evaluated (22 small lymphocytic, 11 lymphoplasmacytic, 25 marginal zone and 3 CD5-negative non-Hodgkin lymphomas not otherwise specified). Further two patients were excluded for lack of essential data; six patients were withdrawn before the third cycle because of WHO grade III and IV toxicity. At the final evaluation, the overall response rate was 83% with 40.7% of complete remission. Intention-to-treat analysis showed that at the median follow-up of 36 months, overall survival, progression-free survival and failure-free survival were respectively 78%, 60% and 46%; remission duration among the 49 patients achieving complete remission/partial remission at the end of treatment was 65% (44–78) without significant differences between the main histotypes. The most frequent grade III and IV toxic events were haematological (neutropaenia 34%, anaemia 18% and thrombocytopaenia 11%) and infectious (10%). FC is effective for advanced untreated INFL. Early deaths and haematological toxicity suggest careful patient selection and monitoring.

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Acknowledgements

We would like to thank Dr. A. Sirotti (Department of Oncology and Hematology, University of Modena and Reggio Emilia) for her support in data collection and management. This study was supported by a grant (Ricerca Corrente) from the Italian Ministry of Health to Ospedale Maggiore IRCCS, Milan, Italy, and a grant from Associazione Angela Serra, Modena, Italy.

The authors have declared no conflicts of interest.

Author information

Authors and Affiliations

  1. Unità Operativa Ematologia 1, Fondazione IRCCS, Cà Granda, Ospedale Maggiore Policlinico, Dipartimento Scienze Mediche, Università degli Studi, Via F. Sforza 35, 20122, Milan, Italy

    Andrea Ferrario, Maria Cecilia Goldaniga & Luca Baldini

  2. Servizio di Ematologia, Arcispedale S. Maria Nuova, Reggio Emilia, Italy

    Francesco Merli

  3. Dipartimento di Oncologia ed Ematologia, Università di Modena e Reggio Emilia, Modena, Italy

    Stefano Luminari, Luigi Marcheselli & Massimo Federico

  4. Dipartimento di Ematologia, Azienda Ospedaliera Bianchi-Melacrino-Morelli, Reggio Calabria, Italy

    Caterina Stelitano

  5. Divisione di Ematologia, Azienda Ospedaliera “Papardo”, Messina, Italy

    Donato Mannina

  6. Ematologia e Immunoematologia, Ospedale S. Vincenzo, Taormina, Italy

    Mario Russo

  7. Divisione di Ematologia, Ospedale Moscati, Taranto, Italy

    Patrizio Mazza

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  1. Andrea Ferrario
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  8. Luigi Marcheselli
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  9. Maria Cecilia Goldaniga
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  10. Massimo Federico
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  11. Luca Baldini
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for the Gruppo Italiano per lo Studio dei Linfomi

Corresponding author

Correspondence to Luca Baldini.

Additional information

Other participating institutions include the following: Lombardo M., Oncologia Pescara; Bagnuolo A., Oncologia, Correggio; Nunzi M., Medicina e Oncologia, Terni; Mastrullo L., Ematologia, Ospedale S Gennaro, Napoli; Fregoni V., Oncologia, Istituto scientifico fondazione Maugeri, Pavia; Centurioni R,. Medicina e Ematologia, Civitanova Marche; Giglio G., Az. Osp Cardarelli, Campobasso; Ginaldi L., Università di l’Aquila-Teramo, Teramo, Italy; Riezzo A., Divisione di Ematologia, Trani; Fragasso A., Oncoematologia, Matera; Caparrotti G., Ematologia, Caserta; Partesotti G., Oncologia, Sassuolo; Vallisa D., Ematologia, Piacenza; Girmenia GP, Medicina e Ematologia, Abbiategrasso; Polimeno G., Medicina e Ematologia, Acquaviva delle Fonti; Musolino C., Ematologia, Policlinico, Messina.

A complete list of the GISL centres referring patients for the study is given in a footnote at the end of this article.

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Ferrario, A., Merli, F., Luminari, S. et al. Phase II fludarabine and cyclophosphamide for the treatment of indolent B cell non-follicular lymphomas: final results of the LL02 trialof the Gruppo Italiano per lo Studio dei Linfomi (GISL). Ann Hematol 90, 323–330 (2011). https://doi.org/10.1007/s00277-010-1067-1

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