title: Phase II study of methotrexate, vincristine, pegylated-asparaginase, and dexamethasone (MOpAD) in patients with relapsed/refractory acute lymphoblastic leukemia.
abstract: Newer approaches are needed for the treatment of relapsed and refractory acute lymphoblastic leukemia (ALL). Asparaginase-based regimens are active in the treatment of pediatric ALL and may be important in salvage therapy for adult patients. We conducted a pilot trial combining methotrexate, vincristine, PEGylated-asparaginase, and dexamethasone (MOpAD) in adults with relapsed or refractory ALL. We added tyrosine kinase inhibitors in patients with Philadelphia chromosome positive (Ph+) ALL and rituximab in patients with CD20 positive B-cell ALL. Among 37 patients treated (median age 42 years; median 2 prior therapies), the complete remission (CR) rate was 28% and an overall response rate (ORR) was 39%. The median CR duration was 4.3 months. Patients with Ph+ ALL had CR and ORR of 50% and 67%, respectively and the CR and ORR in patients with T-cell leukemia were 45% and 56%, respectively. The median survival in patients with CR/CRp was 10.4 versus 3.4 months in nonresponders (P = 0.02). The most common grade 3 or 4 nonhematologic toxicities were elevations in bilirubin and transaminases, nausea, peripheral neuropathy, and hyperglycemia, which were managed with supportive care, dose adjustments, and interruptions.
authors.affiliation: Department of Leukemia, University of Texas M. D. Anderson Cancer Center, Houston, Texas.
authors.forename: Tapan M
authors.initials: TM
authors.lastname: Kadia
authors.forename: Hagop M
authors.initials: HM
authors.lastname: Kantarjian
authors.forename: Deborah A
authors.initials: DA
authors.lastname: Thomas
authors.forename: Susan
authors.initials: S
authors.lastname: O'Brien
authors.forename: Zeev
authors.initials: Z
authors.lastname: Estrov
authors.forename: Farhad
authors.initials: F
authors.lastname: Ravandi
authors.forename: Elias
authors.initials: E
authors.lastname: Jabbour
authors.forename: Naveen
authors.initials: N
authors.lastname: Pemmaraju
authors.forename: Naval
authors.initials: N
authors.lastname: Daver
authors.forename: Xuemei
authors.initials: X
authors.lastname: Wang
authors.forename: Preetesh
authors.initials: P
authors.lastname: Jain
authors.forename: Sherry
authors.initials: S
authors.lastname: Pierce
authors.forename: Mark
authors.initials: M
authors.lastname: Brandt
authors.forename: Guillermo
authors.initials: G
authors.lastname: Garcia-Manero
authors.forename: Jorge
authors.initials: J
authors.lastname: Cortes
authors.forename: Gautam
authors.initials: G
authors.lastname: Borthakur
mesh_terms: D000328:Adult; D000368:Aged; D058846:Antibodies, Monoclonal, Murine-Derived / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols; D001215:Asparaginase / Q000008:administration & dosage; D001402:B-Lymphocytes / Q000187:drug effects* / Q000473:pathology; D001663:Bilirubin / Q000097:blood; D003907:Dexamethasone / Q000008:administration & dosage; D005260:Female; D006801:Humans; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage; D008875:Middle Aged; D010865:Pilot Projects; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000097:blood / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage; D012008:Recurrence; D000069283:Rituximab; D016019:Survival Analysis; D013601:T-Lymphocytes / Q000187:drug effects* / Q000473:pathology; D000637:Transaminases / Q000097:blood; D016896:Treatment Outcome; D014750:Vincristine / Q000008:administration & dosage
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D047428:Protein Kinase Inhibitors; D000069283:Rituximab; D014750:Vincristine; D003907:Dexamethasone; D000637:Transaminases; D001215:Asparaginase; D001663:Bilirubin; D008727:Methotrexate