title: High-dose imatinib mesylate combined with vincristine and dexamethasone (DIV regimen) as induction therapy in patients with resistant Philadelphia-positive acute lymphoblastic leukemia and lymphoid blast crisis of chronic myeloid leukemia.
abstract: Imatinib combined with high-dose chemotherapy is now becoming the gold standard for treatment of Philadelphia chromosome-positive acute leukemias. However, in all studies imatinib dosage was tapered to 400-600 mg per day. We decided to initiate a clinical trial to evaluate an opposite strategy based on high-dose imatinib (800 mg per day) combined with a less intensive chemotherapeutic regimen (vincristine and dexamethasone), which we called the DIV induction regimen. Thirty-one patients (18 relapsing or refractory Ph+ acute lymphoblastic leukemias and 13 lymphoid blast crisis chronic myelogenous leukemias) were enrolled. Complete remission (CR) was obtained in 28 out of 30 assessable patients. The median bcr-abl/abl ratio after the induction course was 0.1%. Median time to neutrophil recovery was 21 days. Fungus infections were observed in six patients out of 31 and possibly related to dexamethasone. Neuropathy due to vincristine was noted in 14 cases. Nine out of 19 patients under 55 years received allogenic stem cell transplantation after a median time of 78 days post-CR. Patients older than 55 years experienced a 90% CR rate without additional toxicities, suggesting the DIV regimen may also be proposed as a front line therapy in older patients.
authors.affiliation: Service d'Hématologie Clinique, Hôpital Saint-Louis, Paris, France.
authors.forename: D
authors.initials: D
authors.lastname: Rea
authors.forename: L
authors.initials: L
authors.lastname: Legros
authors.forename: E
authors.initials: E
authors.lastname: Raffoux
authors.forename: X
authors.initials: X
authors.lastname: Thomas
authors.forename: P
authors.initials: P
authors.lastname: Turlure
authors.forename: S
authors.initials: S
authors.lastname: Maury
authors.forename: B
authors.initials: B
authors.lastname: Dupriez
authors.forename: A
authors.initials: A
authors.lastname: Pigneux
authors.forename: B
authors.initials: B
authors.lastname: Choufi
authors.forename: O
authors.initials: O
authors.lastname: Reman
authors.forename: D
authors.initials: D
authors.lastname: Stéphane
authors.forename: B
authors.initials: B
authors.lastname: Royer
authors.forename: M
authors.initials: M
authors.lastname: Vigier
authors.forename: M
authors.initials: M
authors.lastname: Ojeda-Uribe
authors.forename: C
authors.initials: C
authors.lastname: Recher
authors.forename: H
authors.initials: H
authors.lastname: Dombret
authors.forename: F
authors.initials: F
authors.lastname: Huguet
authors.forename: P
authors.initials: P
authors.lastname: Rousselot
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001549:Benzamides; D001752:Blast Crisis / Q000188:drug therapy*; D003907:Dexamethasone / Q000008:administration & dosage; D018572:Disease-Free Survival; D004305:Dose-Response Relationship, Drug; D019008:Drug Resistance, Neoplasm; D006801:Humans; D000068877:Imatinib Mesylate; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy*; D010865:Pilot Projects; D010879:Piperazines / Q000008:administration & dosage; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy*; D011743:Pyrimidines / Q000008:administration & dosage; D014750:Vincristine / Q000008:administration & dosage
chemical_list: D001549:Benzamides; D010879:Piperazines; D011743:Pyrimidines; D014750:Vincristine; D003907:Dexamethasone; D000068877:Imatinib Mesylate