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Dasatinib as first-line treatment for adult patients with Philadelphia chromosome-positive acute lymphoblastic leukemia

Foà, Robin and Vitale, Antonella and Vignetti, Marco and Meloni, Giovanna and Guarini, Anna and De Propris, Maria Stefania and Elia, Loredana and Paoloni, Francesca Paola and Fazi, Paola and Cimino, Giuseppe and Nobile, Francesco and Ferrara, Felicetto and Castagnola, Carlo and Sica, Simona and Leoni, Pietro and Zuffa, Eliana and Fozza, Claudio and Luppi, Mario and Candoni, Anna and Iacobucci, Ilaria and Soverini, Simona and Mandelli, Franco and Martinelli, Giovanni and Baccarani, Michele (2011) Dasatinib as first-line treatment for adult patients with Philadelphia chromosome-positive acute lymphoblastic leukemia. Blood, Vol. 118 (25), p. 6521-6528. eISSN 1528-0020. Article.

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DOI: 10.1182/blood-2011-05-351403

Abstract

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, BCRABL levels of < 103 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.

Item Type:Article
ID Code:7042
Status:Published
Refereed:Yes
Uncontrolled Keywords:Dasatinib, acute lymphoblastic leukemia (ALL), GIMEMA LAL1205 protocol
Subjects:Area 06 - Scienze mediche > MED/15 Malattie del sangue
Divisions:001 Università di Sassari > 03 Istituti > Ematologia
Publisher:American Society of Hematology
eISSN:1528-0020
Additional Information:Presented in part at the 49th American Society of Hematology Congress (2007), the 13th European Hematology Association Congress (2008), and the 50th ASH Congress (2008). - On behalf of the GIMEMAAcute Leukemia Working Party.
Deposited On:31 Jan 2012 12:10

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