Fludarabine, ara-C, novantrone and dexamethasone (FAND) in previously treated chronic lymphocytic leukemia patients.
OBJECTIVE
The objective of improving the quality of responses of chronic lymphocytic leukemia (CLL) patients has led to the design of protocols that combine fludarabine (FDR) with synergistic drugs. We evaluated the efficacy and toxicity of a schedule that includes fludarabine, ara-C, novantrone and dexamethasone (FAND) for the management of previously treated CLL patients under 60 years old.


METHODS
Thirty-one patients underwent FAND treatment. Twenty-three patients had active disease (relapsed patients: 9; unresponsive to prior therapy: 14). Eight patients had a partial response (PR) to prior therapy and were treated with the aim of further reducing residual disease. The FAND schedule included fludarabine (25 mg/m(2) i.v. days 1-3), ara-C (1 g/m(2) i.v. day 1: 8 patients; days 1-2: 23 patients), novantrone (10 mg/m(2) i.v. day 1) and dexamethasone (20 mg i.v. days 1-3). Infection prophylaxis consisted of fluconazole, acyclovir, trimethoprim/sulfamethoxasole and granulocyte colony-stimulating factor (G-CSF) in the presence of severe neutropenia.


RESULTS
A response was observed in 7/14 refractory patients (complete response-CR: 29%), in all 9 relapsed patients (CR: 78%) and in 7/8 patients (CR: 87.5%) treated in PR. Taken together, 18 CRs were obtained and in 14 (78%) this was associated with a flow cytometric remission (CD5+/CD20(weak+) PB lymphocytes: <10%). Severe granulocytopenia occurred after 86 of the 124 administered courses (69%), but only after 10/86 courses (12%) were major infections recorded. In 10/15 mobilized patients (cyclophosphamide + G-CSF: 6 patients; FAND + G-CSF: 9 patients) after FAND > or = 2 x 10(6)/kg CD34+ cells were collected. Nine patients were autografted in CR and showed a longer response duration than the 9 patients in CR who did not receive further therapy after FAND (53 vs 30% at 41 months; p = 0.05).


CONCLUSIONS
FAND associated with extensive infection prophylaxis and G-CSF support is a highly cytoreductive and well-tolerated treatment for CLL patients and in most cases does not hamper subsequent stem cell mobilization.
Mauro
Francesca R
FR
Dipartimento di Biotecnologie Cellulari ed Ematologia, University La Sapienza, via Benevento 6, 00161 Rome, Italy. mauro@bce.med.uniroma1.it
Foa
Robin
R
Meloni
Giovanna
G
Gentile
Massimo
M
Giammartini
Elena
E
Giannarelli
Diana
D
De Propris
Maria Stefania
MS
Rapanotti
Maria Cristina
MC
de Fabritiis
Paolo
P
Mandelli
Franco
F
D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols; D003561:Cytarabine / Q000009:adverse effects / Q000627:therapeutic use*; D003907:Dexamethasone / Q000009:adverse effects / Q000627:therapeutic use*; D018450:Disease Progression; D005260:Female; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D008942:Mitoxantrone / Q000009:adverse effects / Q000627:therapeutic use*; D016019:Survival Analysis; D013997:Time Factors; D014740:Vidarabine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use*
D003561:Cytarabine; D003907:Dexamethasone; D008942:Mitoxantrone; D014740:Vidarabine; C024352:fludarabine