title: Treatment of Philadelphia chromosome-positive acute lymphocytic leukemia with hyper-CVAD and imatinib mesylate.
abstract: Imatinib mesylate, an inhibitor of the Bcr-Abl tyrosine kinase, has modest activity in refractory/relapsed Philadelphia chromosome (Ph)-positive acute lymphocytic leukemia (ALL). Use of concurrent chemotherapy and imatinib mesylate in newly diagnosed Ph-positive ALL was explored. There were 20 patients who received hyper-CVAD (cyclophosphamide, vincristine, Adriamycin, and dexamethasone) and imatinib mesylate followed by imatinib mesylate-based consolidation/maintenance therapy. Of these patients, 11 had de novo disease, 4 were primary failures after induction (without imatinib mesylate), and 5 were in complete remission (CR) after induction (without imatinib mesylate). All 15 patients treated for active disease achieved CR. Within a median of 3.5 months in first CR, 10 patients underwent allogeneic stem cell transplantation (SCT). One patient relapsed after matched related SCT. The other 9 patients remained alive in CR with median follow-up of 12 months after SCT (range, 1+ to 17+ months). Among 10 patients ineligible for (no donor or older age) or refusing allogeneic SCT, 1 patient relapsed after one year. There were 5 patients who remained alive in continuous CR for a median of 20 months (range, 4+ to 24+ months), with 2 older patients dying in CR at 15 and 16 months of comorbid conditions. Molecular CRs were achieved in both groups (SCT or no SCT). Outcome with hyper-CVAD and imatinib mesylate appears better than with prior regimens; continued accrual and longer follow-up of the current cohort is needed.
authors.affiliation: Department of Leukemia, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Blvd, Unit 428, Houston, TX 77030, USA. debthomas@mdanderson.org
authors.forename: Deborah A
authors.initials: DA
authors.lastname: Thomas
authors.forename: Stefan
authors.initials: S
authors.lastname: Faderl
authors.forename: Jorge
authors.initials: J
authors.lastname: Cortes
authors.forename: Susan
authors.initials: S
authors.lastname: O'Brien
authors.forename: Francis J
authors.initials: FJ
authors.lastname: Giles
authors.forename: Steven M
authors.initials: SM
authors.lastname: Kornblau
authors.forename: Guillermo
authors.initials: G
authors.lastname: Garcia-Manero
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Keating
authors.forename: Michael
authors.initials: M
authors.lastname: Andreeff
authors.forename: Sima
authors.initials: S
authors.lastname: Jeha
authors.forename: Miloslav
authors.initials: M
authors.lastname: Beran
authors.forename: Srdan
authors.initials: S
authors.lastname: Verstovsek
authors.forename: Sherry
authors.initials: S
authors.lastname: Pierce
authors.forename: Laurie
authors.initials: L
authors.lastname: Letvak
authors.forename: August
authors.initials: A
authors.lastname: Salvado
authors.forename: Richard
authors.initials: R
authors.lastname: Champlin
authors.forename: Moshe
authors.initials: M
authors.lastname: Talpaz
authors.forename: Hagop
authors.initials: H
authors.lastname: Kantarjian
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use*; D001549:Benzamides; D003520:Cyclophosphamide / Q000008:administration & dosage; D003907:Dexamethasone / Q000008:administration & dosage; D018572:Disease-Free Survival; D004317:Doxorubicin / Q000008:administration & dosage; D006801:Humans; D000068877:Imatinib Mesylate; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy* / Q000401:mortality; D008875:Middle Aged; D010879:Piperazines / Q000627:therapeutic use*; D011743:Pyrimidines / Q000627:therapeutic use*; D033581:Stem Cell Transplantation; D016019:Survival Analysis; D013997:Time Factors; D014184:Transplantation, Homologous; D014750:Vincristine / Q000008:administration & dosage
chemical_list: D000970:Antineoplastic Agents; D001549:Benzamides; D010879:Piperazines; D011743:Pyrimidines; D014750:Vincristine; D003907:Dexamethasone; D004317:Doxorubicin; D000068877:Imatinib Mesylate; D003520:Cyclophosphamide