Dasatinib is a potent BCR-ABL inhibitor effective in chronic myeloid leukemia and Ph ؉ acute lymphoblastic leukemia (ALL) resistant/intolerant to imatinib. In the GIMEMA LAL1205 protocol, patients with newly diagnosed Ph ؉ ALL older than 18 years (with no upper age limit) received dasatinib induction therapy for 84 days combined with steroids for the first 32 days and intrathecal chemotherapy. Postremission therapy was free. Fiftythree patients were evaluable (median age, 53.6 years). All patients achieved a complete hematologic remission (CHR), 49 (92.5%) at day 22. At this time point, 10 patients achieved a BCR-ABL reduction to < 10 ؊3 . At 20 months, the overall survival was 69.2% and disease-free survival was 51.1%. A significant difference in DFS was observed between patients who showed at day 22 a decrease in BCR-ABL levels to < 10 ؊3 compared with patients who never reached these levels during induction. In multivariate analysis, BCR-ABL levels of < 10 ؊3 at day 85 correlated with disease-free survival. No deaths or relapses occurred during induction. Twenty-three patients relapsed after completing induction. A T315I mutation was detected in 12 of 17 relapsed cases. Treatment was well tolerated; only 4 patients discontinued therapy during the last phase of the induction when already in CHR. In adult Ph ؉ ALL, induction treatment with dasatinib plus steroids is associated with a CHR in virtually all patients, irrespective of age, good compliance, no deaths, and a very rapid debulking of the neoplastic clone. IntroductionDespite an improved understanding of the biology of acute lymphoblastic leukemia (ALL), the overall prognosis of adult patients remains unsatisfactory. 1-3 The Philadelphia (Ph) chromosome is the most frequent genetic abnormality in adult ALL; its prevalence increases with age, accounting for 12% to 30% in patients 18 to 35 years of age, 40% to 45% in patients 36 to 50 years of age, 4,5 and Ͼ 50% in patients older than 60 years. 6 The Ph chromosome and BCR-ABL fusion gene have been associated with a highly unfavorable prognosis, independent of age, 7,8 and elderly patients were often treated only with supportive therapy.The tyrosine kinase inhibitor (TKI) imatinib has profoundly altered the management of patients with chronic myeloid leukemia and impacted on the natural course of the disease. 9,10 Imatinib has also been effectively used in Ph ϩ ALL, both in adults and children. [11][12][13] In a GIMEMA study, all 29 Ph ϩ ALL patients aged 60 years of age or older treated with imatinib plus prednisone without chemotherapy as first-line treatment obtained a complete hematologic remission (CHR). 14 The GMALL study group also showed that, in elderly patients with de novo Ph ϩ ALL, induction with imatinib resulted in a significantly higher CR rate and lower toxicity than with chemotherapy. 15 Dasatinib is a second-generation TKI with a 300-fold greater activity than imatinib in vitro. 16,17 Dasatinib has demonstrated a marked efficacy in patients with CML after relapse or resistance to imatinib...

We conclude that IKZF1 deletions are likely to be a genomic alteration that significantly affects the prognosis of Ph-positive ALL in adults.

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