Originally published as JCO Early Release 10.1200/JCO.2005.03.2177 on December 12 2005

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High Complete Remission Rate and Promising Outcome by Combination of Imatinib and Chemotherapy for Newly Diagnosed BCR-ABL–Positive Acute Lymphoblastic Leukemia: A Phase II Study by the Japan Adult Leukemia Study Group

From the Nagoya University Graduate School of Medicine, Nagoya; Nihon University School of Medicine, Tokyo; Toyohashi Municipal Hospital, Toyohashi; Tokyo Metropolitan Komagome Hospital and Jikei University School of Medicine, Tokyo; Saitama Medical School, Saitama; Mie University Graduate School of Medicine, Tsu; Kurashiki Central Hospital, Kurashiki; Minami-Okayama Medical Center, Okayama; Saiseikai Maebashi Hospital, Maebashi; Kanagawa Cancer Center, Yokohama; Nagasaki University Graduate School of Biomedical Sciences, Nagasaki; Kanazawa University Graduate School of Medicine, Kanazawa; and Aichi Cancer Center, Nagoya, Japan

Address reprint requests to: Masamitsu Yanada, Department of Hematology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, Aichi 466-8550, Japan; e-mail: myanada{at}med.nagoya-u.ac.jp

Purpose A novel therapeutic approach is urgently needed for BCR-ABL–positive acute lymphoblastic leukemia (ALL). In this study, we assessed the efficacy and feasibility of chemotherapy combined with imatinib.

Patients and Methods A phase II study of imatinib-combined chemotherapy was conducted for newly diagnosed BCR-ABL–positive ALL in adults. Eighty patients were entered into the trial between September 2002 and January 2005.

Results Remission induction therapy resulted in complete remission (CR) in 77 patients (96.2%), resistant disease in one patient, and early death in two patients, as well as polymerase chain reaction negativity of bone marrow in 71.3%. The profile and incidence of severe toxicity were not different from those associated with our historic chemotherapy-alone regimen. Relapse occurred in 20 patients after median CR duration of 5.2 months. Allogeneic hematopoietic stem-cell transplantation (HSCT) was performed for 49 patients, 39 of whom underwent transplantation during their first CR. The 1-year event-free and overall survival (OS) rates were estimated to be 60.0%, and 76.1%, respectively, which were significantly better than those for our historic controls treated with chemotherapy alone (P < .0001 for both). Among the current trial patients, the probability for OS at 1 year was 73.3% for those who underwent allogeneic HSCT, and 84.8% for those who did not.

Conclusion Our results demonstrated that imatinib-combined regimen is effective and feasible for newly diagnosed BCR-ABL–positive ALL. Despite a relatively short period of observation, a major potential of this treatment is recognized. Longer follow-up is required to determine its overall effect on survival.

Supported by the Grants for cancer from Ministry of Health, Welfare, and Labor and by the Grant for cancer Translational Research Project from Ministry of Education, Culture, Sports, Science, and Technology, Government of Japan.

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

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