Fludarabine, cytosine arabinoside, granulocyte-colony stimulating factor with or without idarubicin in the treatment of high risk acute leukaemia or myelodysplastic syndromes.
ABSTRACT 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.
Article: The clinical outcome of FLAG chemotherapy without idarubicin in patients with relapsed or refractory acute myeloid leukemia.[show abstract] [hide abstract]
ABSTRACT: A refractory and resistant disease to conventional induction chemotherapy and relapsed disease are considered as the most important adverse prognostic factors for acute myeloid leukemia (AML). Sixty-one patients (median age, 33.6 yr) with relapsed or refractory AML were treated with the FLAG regimen that consisted of fludarabine (30 mg/m(2), days 1-5), cytarabine (2.0 g/m(2), days 1-5) and granulocyte colony-stimulating factor. Of the treated patients 29 patients (47.5%) achieved complete remission (CR). Higher CR rates were observed for patients with a first or second relapse as compared to patients with a primary refractory response or relapse after stem cell transplantation (HSCT). There was a significant difference in the response rates according to the duration of leukemia-free survival (pre-LFS) before chemotherapy (P=0.05). The recovery time of both neutrophils (> or =500/microL) and platelets (> or =20,000/microL) required a median of 21 and 18 days, respectively. Treatment-related mortality (TRM) occurred in seven patients (11.4%), of which 71.4% of TRM was caused by an invasive aspergillosis infection. After achieving CR, 18 patients underwent consolidation chemotherapy and six patients underwent allogeneic HSCT. In conclusion, FLAG chemotherapy without idarubicin is a relatively effective and well-tolerated regimen for relapsed or refractory AML and the use of FLAG chemotherapy has allowed intensive post-remission therapy including HSCT.Journal of Korean medical science 06/2009; 24(3):498-503. · 0.84 Impact Factor
Article: Prognostic factors and therapeutic options for relapsed or refractory acute myeloid leukemia.[show abstract] [hide abstract]
ABSTRACT: Considerable progress has been made in the treatment of acute myeloid leukemia (AML); however, current therapeutic results are still unsatisfactory in untreated patients and poorer in those with primary refractory or relapsed disease. The biological and clinical characteristics of relapsed AML are analyzed here. Most relevant literature in English language on relapsed AML from 1990 to 2004 was considered paying particular attention to the heterogeneity of the disease and prognostic factors at the time of relapse; therapeutic results in terms of second complete remission (CR) with conventional chemotherapy, stem cell transplantation and new agents are also summarized. Molecular relapse is a current indication for treatment of acute promyelocytic leukemia (APL); however, data are emerging for the treatment of molecular relapse in AML other than APL, such as AML with t(8;21) and AML with inv(16). Age, duration of first remission and cytogenetics are the most relevant prognostic factors in relapsed AML. Promising therapeutic results have been reported for the antiCD33 monoclonal antibody conjugated with calicheamicin and the new nucleoside analog clofarabine; preliminary studies indicate that FLT3, farnesyl-transferase and bcl-2 inhibitors are active in relapsed AML. All relapsed elderly patients and young adults with CR1 lasting for less than 12 months are ideal candidates for experimental therapies. Efficiently conducted phase II randomized trials are needed in order to achieve relevant information to be translated into phase III trials.Haematologica 09/2004; 89(8):998-1008. · 6.42 Impact Factor