Fludarabine plus cyclophosphamide for the treatment of advanced chronic lymphocytic leukemia.
OBJECTIVE
Therapeutic results in advanced chronic lymphocytic leukemia (CLL) are still unsatisfactory in terms of complete remission achievement and duration, in spite of the extensive use of purine analogs. The objective of this study was to describe the clinical characteristics and treatment results from a series of 32 patients managed with a therapeutic program based on the combination of fludarabine and cyclophosphamide (CTX).


METHODS
Thirty-two patients (median age 63 yr, range 42-75 yr) with newly diagnosed (47%) or refractory-relapsed (53%) CLL were programmed to receive six courses of a 3-d combination of fludarabine at 30 mg/m2/d plus CTX at 300 mg/m2/d. Refractory-relapsed patients had previously received different chemotherapy lines from 1 to 5.


RESULTS
Fourteen of 32 (44%) patients achieved a complete remission, 16 (50%) obtained partial remission and two (6%) failed to respond. The CR rate was higher in untreated patients; in particular, CR was achieved in nine of 15 (60%) newly diagnosed cases as opposed to five of 17 (29%) among pretreated patients. Toxicity was caused by myelosuppression and/or infections in most cases. After a median follow-up of 24 months (range 8-48 months), 20 of 32 patients (62%) are alive, and 14 of 32 (44%) are free from progression. Median overall survival and median time to progression were 35 and 25 months, respectively.


CONCLUSIONS
The combination of fludarabine with CTX is effective in advanced CLL with acceptable toxicity, either as first-line therapy or in refractory-relapsed patients. In particular, a considerable rate of complete remission can be achieved in untreated patients. Myelosuppression represents the major side-effect.
Schiavone
Ettore Mariano
EM
Division of Hematology and Stem Cell Transplantation Unit, Blood Transfusion Service, A.O.R.N. A. Cardarelli, Napoli, Italy. emschia@tin.it
De Simone
Mariacarla
M
Palmieri
Salvatore
S
Annunziata
Mario
M
Pocali
Barbara
B
Copia
Carolina
C
D'Amico
Maria Rosaria
MR
Vecchio
Luigi Del
LD
Ferrara
Felicetto
F
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000633:toxicity; D003520:Cyclophosphamide / Q000008:administration & dosage* / Q000633:toxicity; D005260:Female; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000150:complications / Q000188:drug therapy* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D009503:Neutropenia / Q000139:chemically induced; D009894:Opportunistic Infections / Q000139:chemically induced; D012074:Remission Induction; D016879:Salvage Therapy; D016019:Survival Analysis; D016896:Treatment Outcome; D014740:Vidarabine / Q000008:administration & dosage* / Q000031:analogs & derivatives* / Q000633:toxicity
D003520:Cyclophosphamide; D014740:Vidarabine; C024352:fludarabine