title: Dasatinib as first-line treatment for adult patients with Philadelphia chromosome-positive acute lymphoblastic leukemia.
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. Fifty-three 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.
authors.affiliation: Department of Cellular Biotechnologies and Hematology, Sapienza University of Rome, Via Benevento 6, Rome, Italy. rfoa@bce.uniroma1.it.
authors.forename: Robin
authors.initials: R
authors.lastname: Foà
authors.forename: Antonella
authors.initials: A
authors.lastname: Vitale
authors.forename: Marco
authors.initials: M
authors.lastname: Vignetti
authors.forename: Giovanna
authors.initials: G
authors.lastname: Meloni
authors.forename: Anna
authors.initials: A
authors.lastname: Guarini
authors.forename: Maria Stefania
authors.initials: MS
authors.lastname: De Propris
authors.forename: Loredana
authors.initials: L
authors.lastname: Elia
authors.forename: Francesca
authors.initials: F
authors.lastname: Paoloni
authors.forename: Paola
authors.initials: P
authors.lastname: Fazi
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Cimino
authors.forename: Francesco
authors.initials: F
authors.lastname: Nobile
authors.forename: Felicetto
authors.initials: F
authors.lastname: Ferrara
authors.forename: Carlo
authors.initials: C
authors.lastname: Castagnola
authors.forename: Simona
authors.initials: S
authors.lastname: Sica
authors.forename: Pietro
authors.initials: P
authors.lastname: Leoni
authors.forename: Eliana
authors.initials: E
authors.lastname: Zuffa
authors.forename: Claudio
authors.initials: C
authors.lastname: Fozza
authors.forename: Mario
authors.initials: M
authors.lastname: Luppi
authors.forename: Anna
authors.initials: A
authors.lastname: Candoni
authors.forename: Ilaria
authors.initials: I
authors.lastname: Iacobucci
authors.forename: Simona
authors.initials: S
authors.lastname: Soverini
authors.forename: Franco
authors.initials: F
authors.lastname: Mandelli
authors.forename: Giovanni
authors.initials: G
authors.lastname: Martinelli
authors.forename: Michele
authors.initials: M
authors.lastname: Baccarani
mesh_terms: D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000378:metabolism; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D000069439:Dasatinib; D004334:Drug Administration Schedule; D005260:Female; D005434:Flow Cytometry; D016044:Fusion Proteins, bcr-abl / Q000235:genetics; D015973:Gene Expression Regulation, Leukemic / Q000187:drug effects; D006801:Humans; D016130:Immunophenotyping; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D011743:Pyrimidines / Q000008:administration & dosage / Q000627:therapeutic use*; D012008:Recurrence; D012074:Remission Induction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013256:Steroids / Q000008:administration & dosage; D013844:Thiazoles / Q000008:administration & dosage / Q000627:therapeutic use*; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D015703:Antigens, CD; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D013256:Steroids; D013844:Thiazoles; D016044:Fusion Proteins, bcr-abl; D000069439:Dasatinib