Fludarabine, cytarabine, and granulocyte-colony stimulating factor for the treatment of high risk myelodysplastic syndromes

Ferrara, Felicetto; Leoni, Franco; Pinto, António E.; Mirto, Salvatore; Morra, Enrica; Zagonel, Vittorina; Mele, Giuseppina; Ciolli, Stefania; Magrin, S.; Montillo, Marco

doi:10.1002/(sici)1097-0142(19991115)86:10<2006::aid-cncr18>3.0.co;2-2

Cited by 24 publications

(8 citation statements)

References 25 publications

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“…The FLAG and FLAG‐idarubicin (Ida) regimens, which combine fludarabine (FDR), high dose cytosine arabinoside (ara‐C) and granulocyte colony stimulating factor (G‐CSF) with or without Ida, have recently been used with encouraging results in poor risk acute myeloid leukaemia (AML), MDS and refractory or relapsed acute lymphoblastic leukaemia (ALL) (Estey et al , 1994; Visani et al , 1994; Clavio et al , 1996; Nokes et al , 1997; Parker et al , 1997; Deane et al , 1998; Fleischhack et al , 1998; Montillo et al , 1998; Ferrara et al , 1999; Steinmetz et al , 1999; Jackson et al , 2001). The toxicity of this combination regimen was also found to be low.…”

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confidence: 99%

Fludarabine, cytosine arabinoside, granulocyte‐colony stimulating factor with or without idarubicin in the treatment of high risk acute leukaemia or myelodysplastic syndromes

et al. 2003

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Summary The combination of fludarabine (FDR), high dose cytarabine and granulocyte colony stimulating factor (FLAG) with or without idarubicin (Ida) was used in the treatment of poor risk acute leukaemia or myelodysplastic syndrome (MDS) in a single centre experience. A total of 105 patients were treated over a 4‐year period with 59% achieving a complete remission (CR); no statistical difference observed between FLAG and FLAG‐Ida. For patients responding to FLAG ± Ida, the median event‐free survival (EFS) was 11 months and 23% at 5 years. Such patients proceeded either to further chemotherapy or a haematopoietic stem cell transplant (HSCT). The median EFS (13 months vs. 8 months) and projected 5‐year survival (37% vs. 13%) of patients undergoing HSCT was significantly better than those who did not (P = 0.021). In all, 14 of 72 patients remain alive in continuing CR (median duration 43 months) with 10 of 31 having had a HSCT vs. four of 41 that did not (P = 0·033). Both regimens were well tolerated, with the majority of patients experiencing grade 1 or less non‐haematological toxicity (mainly nausea and vomiting). The median time to neutrophil and platelet recovery was 28 and 31 d, respectively. No significant differences were seen with the addition of ida. There was a 17% incidence of treatment‐related deaths, of which 39% was caused by invasive aspergillus infection. The results show that FLAG ± Ida is an effective and well‐tolerated remission induction regimen for poor risk leukaemia and MDS.

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Fludarabine, cytosine arabinoside, granulocyte‐colony stimulating factor with or without idarubicin in the treatment of high risk acute leukaemia or myelodysplastic syndromes

et al. 2003

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“…The combination of fludarabine phosphate (FAMP) with intermediate-or high-dose cytarabine (ARA-C) and G-CSF (FLAG) has been proved to be a potentially useful chemotherapy regimen for poor prognosis AML, such as secondary or relapsing AML (8)(9)(10)(11), as well as for high-risk MDS (12,13). In addition, the FLAG regimen delivers high-dose treatment without increasing overall toxicity, an approach which is of particular interest in older patients (12,13). The therapeutic combination is based on the synergistic action of FAMP and ARA-C in increasing two-fold the intracellular concentration of the active ARA-C metabolite ARA-CTP (14).…”

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confidence: 99%

De novo acute myeloid leukemia with multilineage dysplasia: treatment results and prognostic evaluation from a series of 44 patients treated with fludarabine, cytarabine and G‐CSF (FLAG)

Ferrara

Palmieri

Pocali

et al. 2002

European J of Haematology

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Multilineage dysplasia per se is not an adverse prognostic factor in AML patients treated with the FLAG regimen. Favorable results are obtained in patients with intermediate karyotype, while in those with adverse cytogenetics new approaches are clearly needed. The toxicity of the regimen is also acceptable in the elderly, and following induction/consolidation, most patients may be submitted to transplantation procedures.

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“…In this study, patients with secondary AML had been given a different induction with the FLAG regimen, therefore one could hypothesize that the worse outcome of this subgroup would depend on different induction therapy. However, FLAG in turn represents an effective therapeutic option for induction of CR in poor‐risk AML and MDS (Ferrara et al , 1999, 2002). In addition, all patients with secondary AML received IDA in the consolidation, suggesting that the poorer outcome was not related to different induction/consolidation therapy.…”

Section: Discussionmentioning

confidence: 99%

High‐dose idarubicin and busulphan as conditioning to autologous stem cell transplantation in adult patients with acute myeloid leukaemia

Ferrara¹,

Palmieri²,

Simone³

et al. 2004

Br J Haematol

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Summary Between 30 and 50% of patients with acute myeloid leukaemia (AML) relapse after autologous stem cell transplantation (ASCT). One possibility of reducing the relapse rate could be the adoption of conditioning regimens specifically designed for AML. We report treatment results achieved with a new conditioning for ASCT, based on high‐dose idarubicin (IDA) plus oral busulphan. Patients (n = 40) were conditioned with a regimen consisting of 3 d continuous intravenous infusion IDA at 20 mg/m2, followed by 4 d conventional dose oral busulphan. Unpurged peripheral blood stem cells were used in all cases. All patients had non‐M3‐AML and were in first complete remission (CR). The median number of CD34+ cells infused was 6·9 × 106/l (2·6–24). No case of transplant‐related mortality occurred. In all cases, left ventricular ejection fraction remained unmodified after ASCT. Thirty‐three of 40 patients (82%) had grade 3–4 mucositis requiring total parenteral nutrition in all cases. After a median follow up for surviving patients of 32 months from ASCT, 30 patients (75%) are alive and 26 (65%) are in continuous CR. Our data show that a conditioning regimen based on high‐dose IDA plus busulphan results in an encouraging reduction of the relapse rate after ASCT in AML.

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Fludarabine, cytarabine, and granulocyte-colony stimulating factor for the treatment of high risk myelodysplastic syndromes

Cited by 24 publications

References 25 publications

Fludarabine, cytosine arabinoside, granulocyte‐colony stimulating factor with or without idarubicin in the treatment of high risk acute leukaemia or myelodysplastic syndromes

Fludarabine, cytosine arabinoside, granulocyte‐colony stimulating factor with or without idarubicin in the treatment of high risk acute leukaemia or myelodysplastic syndromes

De novo acute myeloid leukemia with multilineage dysplasia: treatment results and prognostic evaluation from a series of 44 patients treated with fludarabine, cytarabine and G‐CSF (FLAG)

High‐dose idarubicin and busulphan as conditioning to autologous stem cell transplantation in adult patients with acute myeloid leukaemia

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