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Previous Volume 338:1506-1514 May 21, 1998 Number 21 Next

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ABSTRACT

Background To determine whether chlorambucil treatment benefits patients with indolent chronic lymphocytic leukemia (CLL), we conducted two randomized trials in 1535 patients with previously untreated stage A CLL.

Methods In the first trial, 609 patients were randomly assigned to receive either daily chlorambucil or no treatment; in the second trial, 926 patients were randomly assigned to receive either intermittent chlorambucil plus prednisone or no treatment. Median follow-up for the first and second trials exceeded 11 and 6 years, respectively. The end points were overall survival, response to treatment, and disease progression.

Results Treatment of indolent CLL did not increase survival in either trial. In the treated group, as compared with the untreated group, the relative risk of death was 1.14 (95 percent confidence interval, 0.92 to 1.41; P=0.23) in the first trial and 0.96 (95 percent confidence interval, 0.75 to 1.23; P=0.74) in the second trial, with 76 percent and 69 percent of patients, respectively, having a response to therapy. Although chlorambucil slowed disease progression, there was no effect on overall survival. In the untreated group in the first trial, 49 percent of patients did not have progression to more advanced disease and did not need therapy after follow-up of more than 11 years; however, 27 percent of patients with stage A CLL died of causes related to the disease.

Conclusions Chlorambucil does not prolong survival in patients with stage A CLL. Since deferring therapy until the disease progresses to stage B or C does not compromise survival, treatment of indolent CLL is unnecessary.

Source Information

From the Unité d'Immuno-Hématologie et d'Immunopathologie, Institut Pasteur, Paris (G.D.); Département d'Hématologie, Hôpital Pitié-Salpêtrière, Paris (K.M., J.-L.B.); Service des Maladies du Sang, Centre Hospitalier Régional–Hôpital Sud, Amiens (B. Desablens); Service des Maladies du Sang, Hôpital Claude Huriez, Lille (B.C.); Service des Maladies du Sang, Centre Hospitalier Universitaire–Hôpital Lapeyronie, Montpellier (M.N.); Service de Médecine G, Centre Hospitalier Régional–Hôpital Sud, Rennes (R.L.); Service Hématologie Clinique, Centre Hospitalier Universitaire de Caen, Caen (M.L.); Département d'Hématologie, Centre Hospitalier Universitaire–Hôpital Nord, Saint-Etienne (J.J.); Onco-Hématologie, Maladies Infectieuses, Centre Hospitalier Avignon–Hôpital Henri Duffaut, Avignon (G.L.); Département d'Hématologie et d'Oncologie Virale, Centre Hospitalier Universitaire–Hôpital Jean Bernard, Poitiers (B. Dreyfus); and Unité d'Hematologie Clinique, Hôtel-Dieu, Clermont-Ferrand (P.T.) — all in France. Other authors were François-Louis Turpin, M.D. (Oncologie Médicale et Hématologie, Centre René Huguenin, St. Cloud, France), Gérard Tertian, M.D. (Laboratoire d'Hématologie, d'Immunologie, et de Cytogénétique, Hôpital Bicêtre, Le Kremlin Bicêtre, France), and Agnès Bichoffe, M.D. (Département de Médecine Interne, Centre Hospitalier Général de Montluçon, Montluçon, France).

Address reprint requests to Dr. Dighiero at Unité d'Immuno-Hématologie et d'Immunopathologie, Institut Pasteur, 28 rue du Dr. Roux, F-75724 Paris CEDEX 15, France.

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