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Lymphomas

Phase I/II study of 2-chloro-2′-deoxyadenosine with cyclophosphamide in patients with pretreated B cell chronic lymphocytic leukemia and indolent non-Hodgkin's lymphoma

Leukemia volume 14, pages 1136–1142 (2000)Cite this article

Abstract

Because of their substantial in vitro synergy, we conducted a dose-escalation study of cyclophosphamide (CP) added to 2-chloro-2′-deoxyadenosine (CdA) in patients with previously treated chronic lymphocytic leukemia and non-Hodgkin's lymphoma. CdA was given at a fixed dose (5.6 mg/m2/day) as a 2-h intravenous (i.v.) infusion, immediately followed by a 1-h i.v. infusion of CP, for 3 days. The initial daily CP dose was 200 mg/m2, and was escalated by 100 mg/m2 increments in successive cohorts of three to six patients to determine the maximum-tolerated dose (MTD). Additional patients were included at the MTD to extend toxicity and response analysis. Twenty-six patients received 68 cycles of chemotherapy. The MTD of CP after CdA 5.6 mg/m2, was 300 mg/m2. Acute neutropenia was the dose-limiting toxicity of this regimen, which was otherwise well tolerated. Delivery of repeated cycles was not feasible in eight patients (31%) because of prolonged thrombocytopenia. Severe infections were seen in three of 68 cycles (4%). The overall response rate was 58% (15 of 26; 95% CI, 36–76%), with 15% complete responses and 42% partial responses. These data show the feasibility of the association of CdA with CP. Given the response rate observed, further studies of this regimen are warranted in untreated patients, in particular with chronic lymphocytic leukemia and with Waldenström macroglobulinemia.

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Acknowledgements

This work was supported by grant No. 7.4556.97 from the ‘Fonds National pour la Recherche Scientifique’, and by the ‘Fondation Salus Sanguinis’.

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Authors and Affiliations

  1. Departments of Hematology and Radiology, Cliniques Universitaires Saint-Luc, Université Catholique de Louvain, Brussels, Belgium

    E Van Den Neste, JL Michaux, A Delannoy, L Michaux, N Straetmans, E Coche, T Duprez & A Ferrant

  2. Department of Hematology, Cliniques Universitaires UCL de Mont-Godinne, Yvoir, Belgium

    I Louviaux, A Sonet, A Bosly & C Doyen

  3. Department of Hematology, Centre d'Hémato-Oncologie de Charleroi, Charleroi, Belgium

    P Mineur & M André

  4. Department of Radiology, Cliniques Saint-Jean, Brussels, Belgium

    C Venet

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Van Den Neste, E., Louviaux, I., Michaux, J. et al. Phase I/II study of 2-chloro-2′-deoxyadenosine with cyclophosphamide in patients with pretreated B cell chronic lymphocytic leukemia and indolent non-Hodgkin's lymphoma. Leukemia 14, 1136–1142 (2000). https://doi.org/10.1038/sj.leu.2401783

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