Conventional dose fludarabine-based regimens are effective but have excessive toxicity in elderly patients with refractory chronic lymphocytic leukemia.
The best approach to elderly patients with relapsing chronic lymphocytic leukemia (CLL) or disease refractory to conventional therapy with alkylating agents has not yet been established. Fludarabine and its combination with mitoxantrone and/or cyclophosphamide, which is the most effective treatment in younger patients, has not been extensively utilized in the elderly CLL. Here we report our results with fludarabine-based chemotherapy in 32 previously treated patients over the age of 65 years. The overall response rate was 59% with no complete remission, 3 nodular partial remissions and 16 partial remissions. The median time to progression of disease was 7 months. Only 10 patients completed the entire treatment program, because of poor compliance due to toxicity. Eight patients developed neutropenic fever, 14 severe bacterial infections and 2 patients showed progressive encephalopathy. For comparison, in a younger group of patients with refractory CLL (< 65 years), 38 of 50 patients completed the treatment plan, and the ORR was 80% (10 CR, 11 PR-nodular, 19 PR) with a median response of 12 months. Neutropenic fever was diagnosed in 10 and severe bacterial infection in 4 patients. In conclusion, fludarabine-based chemotherapy is effective for refractory CLL, however, excessive toxicity such as severe infections and neurological complications, do not allow completion of treatment in the majority of the elderly patients. Because maintenance of a good quality of life should be the main goal in the elderly CLL population, dose reduction of fludarabine and the appropriate use of myeloid growth factors and prophylactic antibiotics appear mandatory in this group of patients.
Shvidel
Lev
L
Hematology Institute, Kaplan Medical Center, Rehovot 76100, Israel.
Shtalrid
Mordechai
M
Bairey
Osnat
O
Rahimi-Levene
Naomi
N
Lugassy
Gilles
G
Shpilberg
Ofer
O
Polliack
Aaron
A
Berrebi
Alain
A
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D003520:Cyclophosphamide / Q000008:administration & dosage; D004305:Dose-Response Relationship, Drug; D064420:Drug-Related Side Effects and Adverse Reactions; D005260:Female; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D008942:Mitoxantrone / Q000008:administration & dosage; D012074:Remission Induction; D016879:Salvage Therapy; D015996:Survival Rate; D016896:Treatment Outcome; D014740:Vidarabine / Q000008:administration & dosage / Q000031:analogs & derivatives*
D003520:Cyclophosphamide; D008942:Mitoxantrone; D014740:Vidarabine; C024352:fludarabine