title: Final report of a phase II study of imatinib mesylate with hyper-CVAD for the front-line treatment of adult patients with Philadelphia chromosome-positive acute lymphoblastic leukemia.
abstract: We have previously reported on the efficacy and tolerability of hyper-CVAD regimen (cyclophosphamide, vincristine, Adriamycin, and dexamethasone) and imatinib followed by imatinib-based consolidation/maintenance therapy in 20 patients with newly diagnosed Philadelphia-positive acute lymphoblastic leukemia. Here, we present the 13-year follow up of our study. Fifty-four patients with newly diagnosed Philadelphia-positive acute lymphoblastic leukemia were enrolled: 39 (72%) with de novo disease, 6 (11%) whose disease was primary refractory after induction (without a tyrosine kinase inhibitor), and 9 (17%) in complete remission after one course of induction therapy (without tyrosine kinase inhibitor). Forty-two (93%) of the 45 patients treated for active disease achieved complete remission, one achieved complete remission with incomplete recovery of platelets, one achieved partial remission and one died during induction. Nineteen (35%) patients are alive and 18 are in complete remission. The 5-year overall survival rate for all patients was 43%. Significant negative predictors of overall survival were age over 60 years, p190 molecular transcript, and active disease at enrollment. Sixteen (30%) patients underwent allogeneic stem cell transplantation. Median overall survival was not significantly greater for patients who underwent transplant. Patients with residual molecular disease at three months had improved complete remission duration with transplant. The median time to hematologic recovery and severe toxicities with combination were not significantly different from those observed with conventional chemotherapy. Only one patient discontinued therapy due to toxicity. HyperCVAD chemotherapy and imatinib is an effective regimen for Philadelphia-positive acute lymphoblastic leukemia. Transplant may not be indicated in all patients with Philadelphia-positive acute lymphoblastic leukemia. (clinicaltrials.gov identifier: NCT00038610).
authors: Department of Leukemia, The University of Texas M. D. Anderson Cancer Center, Houston, TX, USA.
authors: Naval
authors: N
authors: Daver
authors: Department of Leukemia, The University of Texas M. D. Anderson Cancer Center, Houston, TX, USA.
authors: Deborah
authors: D
authors: Thomas
authors: Department of Leukemia, The University of Texas M. D. Anderson Cancer Center, Houston, TX, USA.
authors: Farhad
authors: F
authors: Ravandi
authors: Department of Leukemia, The University of Texas M. D. Anderson Cancer Center, Houston, TX, USA.
authors: Jorge
authors: J
authors: Cortes
authors: Department of Leukemia, The University of Texas M. D. Anderson Cancer Center, Houston, TX, USA.
authors: Rebecca
authors: R
authors: Garris
authors: Department of Leukemia, The University of Texas M. D. Anderson Cancer Center, Houston, TX, USA.
authors: Elias
authors: E
authors: Jabbour
authors: Department of Leukemia, The University of Texas M. D. Anderson Cancer Center, Houston, TX, USA.
authors: Guillermo
authors: G
authors: Garcia-Manero
authors: Department of Leukemia, The University of Texas M. D. Anderson Cancer Center, Houston, TX, USA.
authors: Gautam
authors: G
authors: Borthakur
authors: Department of Leukemia, The University of Texas M. D. Anderson Cancer Center, Houston, TX, USA.
authors: Tapan
authors: T
authors: Kadia
authors: Department of Leukemia, The University of Texas M. D. Anderson Cancer Center, Houston, TX, USA.
authors: Michael
authors: M
authors: Rytting
authors: Department of Leukemia, The University of Texas M. D. Anderson Cancer Center, Houston, TX, USA.
authors: Marina
authors: M
authors: Konopleva
authors: Department of Leukemia, The University of Texas M. D. Anderson Cancer Center, Houston, TX, USA.
authors: Hagop
authors: H
authors: Kantarjian
authors: Department of Leukemia, The University of Texas M. D. Anderson Cancer Center, Houston, TX, USA sobrien@mdanderson.org.
authors: Susan
authors: S
authors: O'Brien
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001549:Benzamides / Q000008:administration & dosage; D003520:Cyclophosphamide / Q000009:adverse effects / Q000627:therapeutic use; D003907:Dexamethasone / Q000009:adverse effects / Q000627:therapeutic use; D004317:Doxorubicin / Q000009:adverse effects / Q000627:therapeutic use; D005500:Follow-Up Studies; D006801:Humans; D000068877:Imatinib Mesylate; D060828:Induction Chemotherapy; D060046:Maintenance Chemotherapy; D008875:Middle Aged; D010879:Piperazines / Q000008:administration & dosage; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality; D011743:Pyrimidines / Q000008:administration & dosage; D019233:Retreatment; D012307:Risk Factors; D016896:Treatment Outcome; D014750:Vincristine / Q000009:adverse effects / Q000627:therapeutic use; D055815:Young Adult
chemical_list: D001549:Benzamides; D010879:Piperazines; D011743:Pyrimidines; D014750:Vincristine; D003907:Dexamethasone; D004317:Doxorubicin; D000068877:Imatinib Mesylate; D003520:Cyclophosphamide