Clinical study of Mito-FLAG regimen in treatment of relapsed acute myeloid leukemia

Abstract

Patients with relapsed acute myeloid leukemia (AML) have unfavorable prognosis and require innovative therapeutic approaches. In this study we used fludarabine combined with a middle dose of cytosine arabinoside (Ara-C), mitoxantrone and granulocyte-colony stimulating factor (G-CSF) as a salvage therapy for patients with relapsed AML in China. Forty-five patients with relapsed AML were treated with the Mito-FLAG regimen consisting of mitoxantrone (7 mg/m2, day 1, 3 and 5), fludarabine (30 mg/m2, days 1–5), Ara-C (1 g/m2, over 3 h every 12 h, days 1–5) and G-CSF [5 μg/kg/day subcutaneously from day 0 until the white blood count (WBC) was >20×109/l]. Patients with a partial response (PR) received another course of the same regimen. Patients with a suitable donor and aged <50 years received allogeneic stem cell transplantation (allo-SCT). Twenty-three patients (51%) and 3 patients (7%) achieved complete remission (CR) and PR, respectively, following one or two courses of Mito-FLAG, and the overall response (OR) rate was 58%. Nine patients (20%) received allo-SCT and 4 patients (9%) succumbed early. Hematological toxicity and infections were the most prominent toxicities of this regimen. Other toxicities included nausea, vomiting, bleeding, hyperbilirubinemia, renal toxicity and arrhythmia. The probability of overall survival (OS) at 4 years was 19% (95% CI, 11–26%) and the probability of 4-year disease-free survival (DFS) was 29% for all 23 patients in CR (95% CI, 18–41%). Our data suggest that Mito-FLAG is a highly effective and well-tolerated salvage regimen for relapsed AML.

Long‐term follow‐up of Cladribine, high‐dose Cytarabine, and Idarubicin as salvage treatment for relapsed acute myeloid leukemia and literature review

“…Thus, the lower TRM in their study has to be evaluated in the light of our protocol amendment. Altogether, a treatment‐related mortality of 10% in this high‐risk patient population appears to be in line with results of other salvage regimens that include fludarabine or cladribine in this setting (TRM 8%‐18%) …”

“…Altogether, a treatment-related mortality of 10% in this high-risk patient population appears to be in line with results of other salvage regimens that include fludarabine or cladribine in this setting (TRM 8%-18%). 6,34 Long-time survival in relapsed AML is only achieved in the group which proceeds to allogeneic stem cell transplantation. 35 Even patients in CR survived <1 year without transplantation in this study and by Fridle et al 24 These findings emphasize that a curative option in the setting of relapsed AML can only be achieved if the salvage chemotherapy can be consolidated with an allogeneic stem cell transplantation.…”

How I treat refractory and early relapsed acute myeloid leukemia

“…Outside trials, we use FLA-IDA as a salvage regimen. 20,45,68,69 If there are no infectious complications we do not add G-CSF to this regimen as there is no data supporting its use. However, idarubicin as an anthracycline appears to be an important drug in this combination as FLA alone (fludarabine, high-dose cytosine) was inferior to cytosine arabinoside, daunorubicin, and etoposide as reinduction in a study for relapsed/refractory patients.…”

The fludarabine, cytarabine, and granulocyte colony‐stimulating factor (FLAG) chemotherapy regimen is an alternative to anthracycline‐based therapy for the treatment of acute myeloid leukemia for patients with pre‐existing cardiac disease

“…Although cytarabine remains one of the most active agents in AML, its activity can be enhanced by the purine analogue fludarabine . The FLAG regimen has been used in fit patients with minimal comorbidities for the treatment of newly diagnosed and primarily refractory or relapsed AML with CR rates between 45.5% and 68% and acceptable toxicity . As FLAG has not previously been evaluated in patients ineligible for anthracycline‐based chemotherapy, we conducted an analysis of patients treated at our center where we have been using FLAG primarily for such patients.…”