title: Intermittent 2-hour-infusion of cladribine as first-line therapy or in first relapse of progressive advanced low-grade and mantle cell lymphomas.
abstract: Aim of this multicenter-study was to evaluate rate and duration of remissions and to examine toxicity of cladribine in low-grade lymphomas as first-line therapy or in first relapse using intermittent 2-hour-infusion of cladribine. A total of 294 courses, median of 5 courses per patient, were administered to 66 evaluable patients (53 previously untreated, 13 relapsed) with 5 mg/m2 cladribine given as intermittent 2-hour-infusion over 5 consecutive days for a maximum of 6 cycles every four weeks. Entities: 26 follicle center, 20 lymphoplasmacytoid, 12 mantle cell, 6 T-cell, 2 marginal zone lymphomas. Fifty of 66 patients responded to cladribine corresponding to an overall response rate of 76% (95% confidence interval (95% CI): 64%-85%) with 38% CR (95% CI: 26%-51%) and a median time of remission duration of 23 months (range 6-45+). The overall survival rate at 48 months was 72%. For 49 previously untreated patients with B-cell lymphomas the overall response rate was 86% (95% CI: 73%-94%) with a high CR rate of 43% (95% CI: 29%-58%). Response rate for the group of 23 previously untreated patients with follicle center lymphomas was high with 96% overall response (95% CI: 78%-100%) and 57% CR rate (95% CI: 34%-77%). Cladribine also showed activity in patients with mantle cell lymphomas achieving a response rate of 58% (95% CI: 28%-85%). Myelosuppression was the major toxicity with 17% neutropenia grade 3 and 4. Thrombocytopenia was rare with only 2% grade 3 and 4. A prolonged CD4-lymphocytopenia was observed in all patients. Life threatening complications were not observed. These results confirm the major single-agent activity of cladribine in a large cohort of patients with untreated low-grade lymphomas using the intermittent 2-hour-infusion dosage-regimen. To improve treatment results furthermore, cladribine should be combined with other agents active in low-grade lymphomas.
authors.affiliation: Med. Klinik III, Johann Wolfgang Goethe-Universitätsklinik, Frankfurt/Main, Germany. rummel@em.uni-frankfurt.de
authors.forename: M J
authors.initials: MJ
authors.lastname: Rummel
authors.forename: K U
authors.initials: KU
authors.lastname: Chow
authors.forename: E
authors.initials: E
authors.lastname: Jäger
authors.forename: L
authors.initials: L
authors.lastname: Leimer
authors.forename: D K
authors.initials: DK
authors.lastname: Hossfeld
authors.forename: L
authors.initials: L
authors.lastname: Bergmann
authors.forename: H D
authors.initials: HD
authors.lastname: Peters
authors.forename: M L
authors.initials: ML
authors.lastname: Hansmann
authors.forename: A
authors.initials: A
authors.lastname: Meyer
authors.forename: D
authors.initials: D
authors.lastname: Hoelzer
authors.forename: P S
authors.initials: PS
authors.lastname: Mitrou
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D017338:Cladribine / Q000627:therapeutic use*; D018450:Disease Progression; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D005858:Germany; D006801:Humans; D007262:Infusions, Intravenous; D020522:Lymphoma, Mantle-Cell / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D008228:Lymphoma, Non-Hodgkin / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D008875:Middle Aged; D012008:Recurrence; D012074:Remission Induction; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D017338:Cladribine