Fludarabine, ara-C, novantrone and dexamethasone (FAND) in previously treated chronic lymphocytic leukemia patients

Francesca R. Mauro, Robin Foa, Giovanna Meloni, Massimo Gentile, Elena Giammartini, Diana Giannarelli, Maria Stefania De Propris, Maria Cristina Rapanotti, Paolo De Fabritiis, Franco Mandelli

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

Background and Objectives. 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. Design and 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/m2 i.v. days 1-3), ara-C (1 g/m2 i.v. day 1: 8 patients; days 1-2: 23 patients), novantrone (10 mg/m2 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+/CD20weak+ 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 ≥ 2×106/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). Interpretation and 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.

Original languageEnglish
Pages (from-to)926-933
Number of pages8
JournalHaematologica
Volume87
Issue number9
Publication statusPublished - Sep 1 2002

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Mitoxantrone
Cytarabine
B-Cell Chronic Lymphocytic Leukemia
Dexamethasone
Granulocyte Colony-Stimulating Factor
fludarabine
Appointments and Schedules
Infection
Hematopoietic Stem Cell Mobilization
Therapeutics
Agranulocytosis
Trimethoprim
Acyclovir
Fluconazole

Keywords

  • Chronic lymphocytic leukemia
  • Cytarabine
  • Dexamethasone
  • Fludarabine
  • Mitoxantrone
  • Treatment

ASJC Scopus subject areas

  • Hematology

Cite this

Mauro, F. R., Foa, R., Meloni, G., Gentile, M., Giammartini, E., Giannarelli, D., ... Mandelli, F. (2002). Fludarabine, ara-C, novantrone and dexamethasone (FAND) in previously treated chronic lymphocytic leukemia patients. Haematologica, 87(9), 926-933.

Fludarabine, ara-C, novantrone and dexamethasone (FAND) in previously treated chronic lymphocytic leukemia patients. / Mauro, Francesca R.; Foa, Robin; Meloni, Giovanna; Gentile, Massimo; Giammartini, Elena; Giannarelli, Diana; De Propris, Maria Stefania; Rapanotti, Maria Cristina; De Fabritiis, Paolo; Mandelli, Franco.

In: Haematologica, Vol. 87, No. 9, 01.09.2002, p. 926-933.

Research output: Contribution to journalArticle

Mauro, FR, Foa, R, Meloni, G, Gentile, M, Giammartini, E, Giannarelli, D, De Propris, MS, Rapanotti, MC, De Fabritiis, P & Mandelli, F 2002, 'Fludarabine, ara-C, novantrone and dexamethasone (FAND) in previously treated chronic lymphocytic leukemia patients', Haematologica, vol. 87, no. 9, pp. 926-933.
Mauro, Francesca R. ; Foa, Robin ; Meloni, Giovanna ; Gentile, Massimo ; Giammartini, Elena ; Giannarelli, Diana ; De Propris, Maria Stefania ; Rapanotti, Maria Cristina ; De Fabritiis, Paolo ; Mandelli, Franco. / Fludarabine, ara-C, novantrone and dexamethasone (FAND) in previously treated chronic lymphocytic leukemia patients. In: Haematologica. 2002 ; Vol. 87, No. 9. pp. 926-933.
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abstract = "Background and Objectives. 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. Design and 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/m2 i.v. days 1-3), ara-C (1 g/m2 i.v. day 1: 8 patients; days 1-2: 23 patients), novantrone (10 mg/m2 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+/CD20weak+ 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 ≥ 2×106/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). Interpretation and 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.",
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T1 - Fludarabine, ara-C, novantrone and dexamethasone (FAND) in previously treated chronic lymphocytic leukemia patients

AU - Mauro, Francesca R.

AU - Foa, Robin

AU - Meloni, Giovanna

AU - Gentile, Massimo

AU - Giammartini, Elena

AU - Giannarelli, Diana

AU - De Propris, Maria Stefania

AU - Rapanotti, Maria Cristina

AU - De Fabritiis, Paolo

AU - Mandelli, Franco

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N2 - Background and Objectives. 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. Design and 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/m2 i.v. days 1-3), ara-C (1 g/m2 i.v. day 1: 8 patients; days 1-2: 23 patients), novantrone (10 mg/m2 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+/CD20weak+ 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 ≥ 2×106/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). Interpretation and 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.

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KW - Chronic lymphocytic leukemia

KW - Cytarabine

KW - Dexamethasone

KW - Fludarabine

KW - Mitoxantrone

KW - Treatment

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