title: High incidence of complications after 2-chloro-2'-deoxyadenosine combined with cyclophosphamide in patients with advanced lymphoproliferative malignancies.
abstract: The combination of purine analogs with alkylating agents is able to produce a synergistic antitumoral effect. However, the addition of immunosuppressive and DNA-targeting agents might increase purine analog-related complications. The risk for serious complications was evaluated in 38 patients treated with 2-chloro-2'-deoxyadenosine (CDA) and cyclophosphamide (CP). The diagnoses were chronic lymphocytic leukemia (CLL) in 15, Waldenström's macroglobulinemia in 4, mantle cell lymphoma in 6, follicular non-Hodgkin's lymphoma (NHL) in 10, and other low-grade NHL in 3 patients. All patients were pretreated (median: 2 lines, range: 1-5) and 23 (61%) were refractory. The patients received a median of two courses (range: 1-5) of 5.6 mg/m(2) CDA, followed by a median of 200 mg/m(2) CP, for 3 days. The response rate was 51% [complete remission (CR): 14%, partial remission (PR): 38%]. Grade 3/4 infections occurred in 16 (42%) patients. Dose-limiting cytopenias were seen in 22 (58%) patients. In 12 (32%) patients, autoimmune manifestations developed requiring treatment in most of them. Second cancers arose in five (13%) patients (myelodysplastic syndrome/acute myelocytic leukemia in three, lung cancer in two). Multivariate analysis showed that cytopenias, gender (F), prior radiotherapy, and age (>65 years) predicted for the complications seen after CDA-CP. To conclude, because of the high incidence of complications, caution is warranted in selecting patients with advanced lymphoid malignancies for the CDA-CP protocol.
authors.affiliation: Department of Hematology, Cliniques universitaires Saint-Luc, Université catholique de Louvain, 1200 Brussels, Belgium. vandenneste@sang.ucl.ac.be
authors.forename: E
authors.initials: E
authors.lastname: Van Den Neste
authors.forename: L
authors.initials: L
authors.lastname: Michaux
authors.forename: N
authors.initials: N
authors.lastname: Layios
authors.forename: S
authors.initials: S
authors.lastname: Costantini
authors.forename: J
authors.initials: J
authors.lastname: Francart
authors.forename: C
authors.initials: C
authors.lastname: Lambert
authors.forename: A
authors.initials: A
authors.lastname: Sonet
authors.forename: M
authors.initials: M
authors.lastname: André
authors.forename: A
authors.initials: A
authors.lastname: Robert
authors.forename: A
authors.initials: A
authors.lastname: Ferrant
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects*; D017338:Cladribine / Q000008:administration & dosage / Q000009:adverse effects; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D006801:Humans; D007970:Leukopenia / Q000139:chemically induced / Q000453:epidemiology; D008232:Lymphoproliferative Disorders / Q000150:complications* / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D008297:Male; D008875:Middle Aged; D016609:Neoplasms, Second Primary / Q000139:chemically induced / Q000453:epidemiology / Q000209:etiology; D009894:Opportunistic Infections / Q000139:chemically induced / Q000453:epidemiology / Q000382:microbiology; D016019:Survival Analysis
chemical_list: D017338:Cladribine; D003520:Cyclophosphamide