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High incidence of complications after 2-chloro-2’-deoxyadenosine combined with cyclophosphamide in patients with advanced lymphoproliferative malignancies

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Abstract

The combination of purine analogs with alkylating agents is able to produce a synergistic antitumoral effect. However, the addition of immunosuppressive and DNA-targeting agents might increase purine analog-related complications. The risk for serious complications was evaluated in 38 patients treated with 2-chloro-2’-deoxyadenosine (CDA) and cyclophosphamide (CP). The diagnoses were chronic lymphocytic leukemia (CLL) in 15, Waldenström’s macroglobulinemia in 4, mantle cell lymphoma in 6, follicular non-Hodgkin’s lymphoma (NHL) in 10, and other low-grade NHL in 3 patients. All patients were pretreated (median: 2 lines, range: 1–5) and 23 (61%) were refractory. The patients received a median of two courses (range: 1–5) of 5.6 mg/m2 CDA, followed by a median of 200 mg/m2 CP, for 3 days. The response rate was 51% [complete remission (CR): 14%, partial remission (PR): 38%]. Grade 3/4 infections occurred in 16 (42%) patients. Dose-limiting cytopenias were seen in 22 (58%) patients. In 12 (32%) patients, autoimmune manifestations developed requiring treatment in most of them. Second cancers arose in five (13%) patients (myelodysplastic syndrome/acute myelocytic leukemia in three, lung cancer in two). Multivariate analysis showed that cytopenias, gender (F), prior radiotherapy, and age (>65 years) predicted for the complications seen after CDA-CP. To conclude, because of the high incidence of complications, caution is warranted in selecting patients with advanced lymphoid malignancies for the CDA-CP protocol.

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Acknowledgements

This study was supported by grant No. 7.4528.01 and 3.4578.01 from the “Fonds National pour la Recherche Scientifique,” and by the “Fondation Salus Sanguinis.” The authors thank Karine Buysschaert for editorial assistance.

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Authors and Affiliations

  1. Department of Hematology, Cliniques universitaires Saint-Luc, Université catholique de Louvain, 1200, Brussels, Belgium

    E. Van Den Neste, L. Michaux, N. Layios, S. Costantini, C. Lambert & A. Ferrant

  2. Department of Epidemiology, School of Public Health, Faculty of Medicine, Université catholique de Louvain, Brussels, Belgium

    J. Francart & A. Robert

  3. Department of Hematology, Cliniques universitaires UCL de Mont-Godinne, Yvoir, Belgium

    A. Sonet

  4. Department of Hematology, Centre d’Hémato-Oncologie de Charleroi, Charleroi, Belgium

    M. André

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  1. E. Van Den Neste
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Van Den Neste, E., Michaux, L., Layios, N. et al. High incidence of complications after 2-chloro-2’-deoxyadenosine combined with cyclophosphamide in patients with advanced lymphoproliferative malignancies. Ann Hematol 83, 356–363 (2004). https://doi.org/10.1007/s00277-004-0858-7

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