title: Cyclophosphamide, fludarabine, alemtuzumab, and rituximab as salvage therapy for heavily pretreated patients with chronic lymphocytic leukemia.
abstract: Patients with relapsed chronic lymphocytic leukemia (CLL) and high-risk features, such as fludarabine refractoriness, complex karyotype, or abnormalities of chromosome 17p, experience poor outcomes after standard fludaradine-based regimens. Alemtuzumab is a chimeric CD52 monoclonal antibody with activity in CLL patients with fludarabine-refractory disease and 17p deletion. We report the outcome for 80 relapsed or refractory patients with CLL enrolled in a phase 2 study of cyclophosphamide, fludarabine, alemtuzumab, and rituximab (CFAR). All patients were assessed for response and progression according to the 1996 CLL-working group criteria. For the intention-to-treat analysis, the overall response rate was 65%, including 29% complete response. The estimated progression-free survival was 10.6 months and median overall survival was 16.7 months. Although we noted higher complete response in high-risk patients after CFAR compared with a similar population who had received fludarabine, cyclophosphamide, and rituximab as salvage therapy, there was no significant improvement in progression-free survival and overall survival appeared worse. CFAR was associated with a high rate of infectious complications with 37 patients (46%) experiencing a serious infection during therapy and 28% of evaluable patients experiencing late serious infections. Although CFAR produced good response rates in this highly pretreated high-risk group of patients, there was no benefit in survival outcomes.
authors.affiliation: Departments of Leukemia, University of Texas M. D. Anderson Cancer Center, Houston, TX, USA.
authors.forename: Xavier C
authors.initials: XC
authors.lastname: Badoux
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Keating
authors.forename: Xuemei
authors.initials: X
authors.lastname: Wang
authors.forename: Susan M
authors.initials: SM
authors.lastname: O'Brien
authors.forename: Alessandra
authors.initials: A
authors.lastname: Ferrajoli
authors.forename: Stefan
authors.initials: S
authors.lastname: Faderl
authors.forename: Jan
authors.initials: J
authors.lastname: Burger
authors.forename: Charles
authors.initials: C
authors.lastname: Koller
authors.forename: Susan
authors.initials: S
authors.lastname: Lerner
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 / Q000008:administration & dosage* / Q000009:adverse effects; D061067:Antibodies, Monoclonal, Humanized; D058846:Antibodies, Monoclonal, Murine-Derived / Q000008:administration & dosage / Q000009:adverse effects; D000912:Antibodies, Neoplasm / Q000008:administration & dosage / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects; D002872:Chromosome Deletion; D002886:Chromosomes, Human, Pair 17; D003131:Combined Modality Therapy; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000009:adverse effects; D018572:Disease-Free Survival; D006801:Humans; D007239:Infections / Q000209:etiology; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000188:drug therapy* / Q000235:genetics / Q000628:therapy*; D008875:Middle Aged; D000069283:Rituximab; D016879:Salvage Therapy; D058496:Smith-Magenis Syndrome; D033581:Stem Cell Transplantation; D014184:Transplantation, Homologous; D014740:Vidarabine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D058846:Antibodies, Monoclonal, Murine-Derived; D000912:Antibodies, Neoplasm; D000074323:Alemtuzumab; D000069283:Rituximab; D003520:Cyclophosphamide; D014740:Vidarabine; C024352:fludarabine