The Clinical Outcome of FLAG Chemotherapy without Idarubicin in Patients with Relapsed or Refractory Acute Myeloid Leukemia

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/m2, days 1-5), cytarabine (2.0 g/m2, 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.

The Clinical Outcome of FLAG Chemotherapy without Idarubicin in Patients with Relapsed or Refractory Acute Myeloid Leukemia

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/m2, days 1-5), cytarabine (2.0 g/m2, 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.

Treatment with IDA-FLAG (idarubicin, fludarabine, cytarabine, G-CSF) Regimen in Children with Myelodysplastic Syndrome and Relapsed/Refractory Acute Myelogenous Leukemia / 대한소아혈액종양학회지

PURPOSE: The prognosis of refractory or relapsed acute myelogenous leukemia (AML) is poor and effective reinduction regimens are rare. Myelodysplastic syndrome (MDS) is a heterogenous group of clonal disorders of hematopoiesis and the outcome for children with MDS is poor, and the optimal treatment of MDS has not been defined. This study was undertaken to investigate the therapeutic results of IDA-FLAG (idarubicin, fludarabine, cytarabine, G-CSF) in children with MDS and relapsed or refractory AML. METHODS: Eleven children with refractory or relapsed AML and ten with MDS were treated with the IDA-FLAG regimen, a combination therapy of idaraubicin (day 1~3, 12 mg/m2/day), fludarabine (day 1~5, 30 mg/m2/day), cytarabine (day 1~5, 2 g/m2/day) and G-CSF (day 0~5, 400 g/m2/day & day 12 up to ANC > 1,000/L, 5 g/kg/day). RESULTS: In AML group, they received a total 15 courses of IDA-FLAG. Complete remission (CR) was achieved in 4/11 (36.4%) with median remission duration of 3 (2~6) months. In MDS group, they received 13 courses of IDA-FLAG and 8 courses of FLAG (IDA-FLAG without idarubicin). CR was achieved in 6/8 (75.0%) with median remission duration of 4 (2~13) months. All the patients experienced grade 4 hematologic toxicities. The median duration of neutropenia (<500/ mm3) and thrombocytopenia (<30,000/mm3) was 23 days (20~46 days) and 23.5 days (16~44 days) in AML, meanwhile those were 18 days (14~30 days) and 16 days (13~32 days) in MDS, respectively. Infectious complications were the main non-hematological toxicity. Two patients died of sepsis and intracerebral hemorrhage on day 7 and 27, respectively. CONCLUSION: IDA-FLAG may be an efficient reinduction therapy for resistant and intensively pretreated AML and an effective regimen for poor prognostic MDS with acceptable toxicity, even though remission duration seems to be relatively short. Therefore, an intensified post-remission therapy seems necessary.