title: A phase II study of cladribine treatment for fludarabine refractory B cell chronic lymphocytic leukemia: results from CALGB Study 9211.
abstract: Cladribine has been reported to have little activity in fludarabine- refractory chronic lymphocytic leukemia (CLL). We sought to determine whether resistance to therapy with cladribine in fludarabine-refractory CLL patients represented primary drug resistance or the inability to tolerate the myelosuppression associated with this therapy. Patients with fludarabine refractory CLL patients without severe thrombocytopenia (platelets >/=50 x 10(9)/l) or granulocytopenia (neutrophils >1.5 x 10(9)/l) were enrolled. All patients received cladribine (0.14 mg/kg) as a 2-h intravenous infusion daily for 5 days, repeated every 4 weeks. Patients received up to six cycles of therapy. Twenty-eight patients enrolled; 13 had intermediate (Rai stage I or II) and 15 high (Rai stage III and IV) risk stages. No patient had a complete remission, but nine (32%; 95% confidence interval, 15-49%) attained a partial remission when assessed using the modified NCI criteria (1996). The median time to relapse for responders was 12 months, while median progression-free survival for the entire group was 9 months (95% confidence interval, 4-14 months). The median overall survival was 2.2 years (95% confidence interval, 0.8-3.1 years). Response was predicted by pre-treatment Rai status with seven of 13 (54%) intermediate risk vs two of 15 (13%) high-risk patients responding (P = 0.04). Toxicity was myelosuppression and infections (grade 3-5: neutropenia 75%, thrombocytopenia 68%, and infections 43%). Cladribine has modest clinical activity and considerable toxicity in a very selected group of patients with fludarabine-refractory CLL lacking pre-treatment neutropenia and thrombocytopenia.
authors.affiliation: Division of Hematology-Oncology, Department of Medicine, The Ohio State University, Columbus, OH 43210, USA.
authors.forename: J C
authors.initials: JC
authors.lastname: Byrd
authors.forename: B
authors.initials: B
authors.lastname: Peterson
authors.forename: L
authors.initials: L
authors.lastname: Piro
authors.forename: A
authors.initials: A
authors.lastname: Saven
authors.forename: J W
authors.initials: JW
authors.lastname: Vardiman
authors.forename: R A
authors.initials: RA
authors.lastname: Larson
authors.forename: C
authors.initials: C
authors.lastname: Schiffer
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D017338:Cladribine / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D016001:Confidence Intervals; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D019008:Drug Resistance, Neoplasm; D006801:Humans; D007262:Infusions, Intravenous; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D008875:Middle Aged; D009367:Neoplasm Staging; D018579:Patient Selection; D015996:Survival Rate; D013997:Time Factors; D014740:Vidarabine / Q000009:adverse effects* / Q000031:analogs & derivatives*
chemical_list: D000970:Antineoplastic Agents; D017338:Cladribine; D014740:Vidarabine; C024352:fludarabine