Combination of Intensive Chemotherapy and Imatinib (IDEAMOP Regimen) for the Treatment of Newly Diagnosed BCR-ABL Positive Acute Lymphoblastic Leukemia; Excellent Efficacy without Increasing Toxicity.

The Philadelphia chromosome, which constitutes BCR-ABL fusion gene, is the most frequent cytogenetic abnormality in adult acute lymphoblastic leukemia (ALL). Although complete remission (CR) is achieved in 50–80% of patients, most of them suffer a relapse, resulting in overall survival (OS) of approximately 10% by standard chemotherapy. Recently, the Japan Adult Leukemia Study Group (JALSG) has started a phase 2 trial for newly diagnosed BCR-ABL positive ALL patients, and 60 patients have been enrolled at this time. We present here the results for the first 41 patients. After screening for BCR-ABL at presentation, those with positive BCR-ABL were treated with IDEAMOP regimen. For remission induction therapy, intensive chemotherapy comprising daunorubicin, cyclophosphamide, vincristine (VCR) and predonisolone (PSL) was combined with imatinib at a dose of 600 mg/day administered from day 8 to day 63. Consolidation therapy consisted of the odd courses with high-dose methotrexate and high-dose cytarabine and the even courses with 600 mg/day of imatinib alone for 28 days, which were repeated alternatively for 4 cycles. Thereafter, patients received maintenance therapy with VCR, PSL and imatinib until 2 years from the date they had attained CR. If an HLA-identical sibling donor was available, allogeneic hematopoietic stem cell transplantation (HSCT) was recommended. HSCT from an alternative donor was used at the discretion of the institution. Between September 2002 and March 2004, a total of 41 patients with newly diagnosed BCR-ABL positive ALL were treated with IDEAMOP. All patients except two cases of early death (95%) attained CR. PCR negativity in bone marrow was achieved in 25% of the patients on day 28, in 57% on day 63, and in up to 73% during the follow-up period. Toxicity of the remission induction therapy was almost similar to that observed for chemotherapy alone. The median time of WBC recovery to at least 1,000/mL was 19 days (range, 14 to 29 days), and the median time of platelet recovery to at least 100,000/mL was 22 days (range, 14 to 30 days). Death occurred in two patients, one for pulmonary bleeding on day 10, and the other for pneumonia on day 32. Interruption of imatinib was implemented for 11 patients (27%) for the following reasons; nausea in 4, GPT elevation in 3, pulmonary bleeding, pneumonia, fluid retention, ileus, amylase elevation in one patient, respectively; however, none of the 39 surviving patients dropped out the protocol due to intolerance of treatment. Four patients had a relapse during consolidation therapy after 4.0, 4.5, 4.9 and 10.3 months of CR. Allogeneic HSCT was performed for 20 patients (9 from a sibling donor, 8 from an unrelated donor, and 3 from unrelated cord blood) during their first CR. The 1-year event-free survival (EFS) and OS rates were estimated at 78% and 88%. Outcomes were superior to those in ALL93 study, where patients were treated with chemotherapy alone, in terms of CR rate, EFS, and OS (P < 0.0001, P < 0.0001, and P = 0.0118, respectively). In summary, our study demonstrated that IDEAMOP produces high-quality CR for a majority of patients with newly diagnosed BCR-ABL positive ALL without an increase in toxicity. This is especially useful for providing patients with a better chance to receive allogeneic HSCT. Long-term efficacy will be addressed in the final analysis of this study.