title: The natural history of fludarabine-refractory chronic lymphocytic leukemia patients who fail alemtuzumab or have bulky lymphadenopathy.
abstract: The natural history and outcome of salvage treatment for patients with fludarabine-refractory chronic lymphocytic leukemia who are either refractory to alemtuzumab ("double-refractory") or ineligible for alemtuzumab due to bulky lymphadenopathy ("bulky fludarabine-refractory") have not been described. We present the outcomes of 99 such patients (double-refractory n = 58, bulky fludarabine-refractory n = 41) undergoing their first salvage treatment at our center. Patients received a variety of salvage regimens including monoclonal antibodies (n = 15), single-agent cytotoxic drugs (n = 14), purine analogue combination regimens (n = 21), intensive combination chemotherapy (n = 36), allogeneic stem cell transplantation (SCT; n = 4), or other therapies (n = 9). Overall response to first salvage therapy other than SCT was 23%, with no complete responses. All four patients who underwent SCT as first salvage achieved complete remission. Early death (within 8 weeks of commencing first salvage) occurred in 13% of patients, and 54% of patients experienced a major infection during therapy. Overall survival was 9 months, with hemoglobin < 11 g/dL (hazard ratio 2.3), hepatomegaly (hazard ratio 2.4), and performance status > or = 2 (hazard ratio 1.9) being significant independent predictors of inferior survival.
authors.affiliation: Department of Leukemia and Stem Cell Transplantation, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
authors.forename: Constantine S
authors.initials: CS
authors.lastname: Tam
authors.forename: Susan
authors.initials: S
authors.lastname: O'Brien
authors.forename: Susan
authors.initials: S
authors.lastname: Lerner
authors.forename: I
authors.initials: I
authors.lastname: Khouri
authors.forename: A
authors.initials: A
authors.lastname: Ferrajoli
authors.forename: S
authors.initials: S
authors.lastname: Faderl
authors.forename: M
authors.initials: M
authors.lastname: Browning
authors.forename: Apostolia M
authors.initials: AM
authors.lastname: Tsimberidou
authors.forename: Hagop
authors.initials: H
authors.lastname: Kantarjian
authors.forename: William G
authors.initials: WG
authors.lastname: Wierda
mesh_terms: D000328:Adult; D000368:Aged; D000074323:Alemtuzumab; D000911:Antibodies, Monoclonal / Q000494:pharmacology* / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D058846:Antibodies, Monoclonal, Murine-Derived; D000912:Antibodies, Neoplasm / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000188:drug therapy* / Q000473:pathology* / Q000628:therapy; D008206:Lymphatic Diseases / Q000188:drug therapy* / Q000473:pathology / Q000628:therapy; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D000069283:Rituximab; D033581:Stem Cell Transplantation / Q000379:methods; D014184:Transplantation, Homologous; D016896:Treatment Outcome; D014740:Vidarabine / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D058846:Antibodies, Monoclonal, Murine-Derived; D000912:Antibodies, Neoplasm; D000970:Antineoplastic Agents; D000074323:Alemtuzumab; D000069283:Rituximab; D014740:Vidarabine; C024352:fludarabine