title: Vinorelbine-based salvage chemotherapy for therapy-refractory aggressive leukaemias.
abstract: This study examined the ability of the semi-synthetic vinca alkaloid, Vinorelbine/Navelbine, to cause apoptotic death in freshly obtained primary leukaemia cells from 53 patients with haematological malignancies, including 22 patients with acute lymphoblastic leukaemia (ALL), 24 patients with chronic lymphocytic leukaemia (CLL), three patients with chronic myeloid leukaemia in blast crisis (CML-BC) and four patients with acute myeloid leukaemia (AML). Vinorelbine caused apoptosis in primary leukaemia cells from 42 (79%) of these leukaemia patients. Objective responses, including complete remission (CR) and CR with incomplete haematological recovery, were achieved in 12 of 17 (71%) patients with aggressive and therapy-refractory leukaemias, including five of nine patients with relapsed ALL, three of three patients with CML-BC and four of five patients with rapidly progressive CLL, who were treated with a vinorelbine-based salvage chemotherapy regimen. Drug sensitivity profiling of multidrug-resistant primary cancer cells using apoptosis assays revealed a significant association between Vinorelbine sensitivity in vitro and the likelihood of an objective clinical response to Vinorelbine-based chemotherapy. Vinorelbine-sensitivity testing of primary leukaemia cells might help tailor Vinorelbine-based salvage regimens to those patients who are most likely to respond.
authors.affiliation: Department of Hematology-Oncology, Parker Hughes Cancer Center, Roseville, MN, USA. fatih_uckun@ih.org
authors.forename: Fatih M
authors.initials: FM
authors.lastname: Uckun
authors.forename: Sanda
authors.initials: S
authors.lastname: Morar
authors.forename: Sanjive
authors.initials: S
authors.lastname: Qazi
mesh_terms: D000293:Adolescent; D000328:Adult; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000494:pharmacology*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D002648:Child; D019008:Drug Resistance, Neoplasm; D004354:Drug Screening Assays, Antitumor / Q000379:methods; D005260:Female; D006801:Humans; D007938:Leukemia / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D012008:Recurrence; D012074:Remission Induction; D016879:Salvage Therapy / Q000379:methods*; D016896:Treatment Outcome; D014407:Tumor Cells, Cultured; D014747:Vinblastine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D000077235:Vinorelbine
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D014747:Vinblastine; D000077235:Vinorelbine