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Blood, 15 February 2004, Vol. 103, No. 4, pp. 1222-1228.
Prepublished online as a Blood First Edition Paper on October 23, 2003; DOI 10.1182/blood-2003-04-1124.


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CLINICAL OBSERVATIONS, INTERVENTIONS, AND THERAPEUTIC TRIALS

Second cancers and late toxicities after treatment of aggressive non-Hodgkin lymphoma with the ACVBP regimen: a GELA cohort study on 2837 patients

Marc André, Nicolas Mounier, Xavier Leleu, Anne Sonet, Pauline Brice, Michel Henry-Amar, Hervé Tilly, Bertrand Coiffier, André Bosly, Pierre Morel, Corinne Haioun, Philippe Gaulard, Felix Reyes, Christian Gisselbrecht, and the Groupe d'Etude des Lymphomes de l'Adulte (GELA)

From the Hematology Department, Centre Hospitalier Notre Dame et reine Fabiola, Charleroi; Hematology Department, Cliniques Universitaires Mont Godinne, Yvoir, Belgium; Hematology Department, Hôpital Saint-Louis, Paris; Hematology Department, Centre Hospitalier Universitaire de Lille; Clinical Research Unit and INSERM CJF 96-03/Grecan, Centre Régional François Baclesse, Caen; Hematology Department, Centre Henri Becquerel, Rouen; Hematology Department, Centre Hospitalier Lyon-Sud, Pierre-Bénite; Hematology Department, Centre Hospitalier de Lens; and Hematology and Pathology Department, Hôpital Henri Mondor, Créteil, France.

The survival of patients with aggressive non-Hodgkin lymphoma (NHL) is increasing, but the incidence of secondary cancer and late toxicity is poorly defined for those treated with cyclophosphamide-hydroxydaunomycin/doxorubicin-Oncovin-prednisone (CHOP)–like chemotherapy. From February 1984 to January 1998, 2837 patients with aggressive NHL received the control-arm chemotherapy adriamycin-cyclophosphamide-vindesine-bleomycin-prednisone (ACVBP) in 3 consecutive Groupe d'Etude des Lymphomes de l'Adulte (GELA) studies. With a median follow-up time of 74 months, the 5-year overall and event-free survival rates were 60% and 52%. Two hundred two occurrences of nonneoplastic late toxicity were reported, resulting in a 5.35% cumulative probability of incidence at 7 years. Eighty-one second tumors developed, for which the 7-year cumulative incidence rate was 2.75%; 64 were solid tumors, and 17 were hematologic malignancies. In multivariate analysis, age was the only risk factor for the second development of cancer. Epidemiologic analysis allowed a comparison of this NHL group with the general population. Considering all tumors, no excess of second cancer was observed. In the male population, however, there was an excess of lung cancer (standardized incidence ratio [SIR], 2.45; P < .001) and myelodysplastic syndrome/acute myelocytic leukemia (MDS/AML) (SIR, 5.65; P = .006), and in the female population there was an excess of MDS/AML (SIR, 19.9; P < .001). With a long follow-up, the ACVBP regimen was highly effective for the treatment of aggressive NHL. Increases occurred in secondary MDS/AML and in lung cancer among men.


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