The Efficacy of Fludarabine, High Dose Cytosine Arabinoside with Granulocyte Colony Stimulating Factor (FLAG) Protocol as Salvage Therapy for Refractory/Relapsed Acute Leukemias in Adult Iraqi Patients

Abstract

Refractory/relapsed acute leukemia has always been a challenging problem for hematologist. Over the past decade emphasis has been made in the development of regimens containing fludarabine, combined with cytosine arabinoside for the treatment of refractory/relapsed acute leukemias. The aim of this study is to evaluate the efficacy and toxicity of the combination of fludarabine, high dose cytarabine, and granulocyte colony stimulating factor in refractory relapsed cases of acute leukaemia, a prospective study is being conducted at the National Center of Hematology and hematology unit/Baghdad teaching hospital from July 2008 to July 2010. Twenty Patients with refractory/relapsed acute leukemia were treated with fludarabine 30 mg/m(2) and cytosine arabinoside (Ara-C) 2 g/m(2) for 5 days, and granulocyte colony stimulating factor G-CSF 300 µg/day from day 0 till neutrophil recovery (ANC > 1.0 × 10(9)/L). Response was evaluated by bone marrow examination on day 30 post chemotherapy. Patients included were refractory acute lymphoblastic leukemia (ALL) (five patients), relapsed ALL (four patients), refractory acute myeloid leukemia (AML) (eight patients), relapsed AML (three patients). Complete remission (CR) was achieved in nine (45 %) patients, while three (15 %) patients got partial remission. Three (15 %) patients died because of post chemotherapy complications and five (25 %) patient failed to achieve remission. Major complications encountered were: anemia, fever, bleeding, mucositis and bacterial infections. FLAG protocol is well tolerated and effective regimen in relapsed/refractory acute leukemias. The toxicity is acceptable, enabling most patients to receive further treatment, including transplantation procedures.

Tumorablative conditioning regimen for haploidentical stem cell transplantation in 102 children with hematologic malignancies: a single-center experience

“…The suppression to host immunity of CY is replaced by fludarabine. Recently, some comparative trials showed that FLAG regimens with or without IDA /Mito produced an excellent effect in children with relapsed/refractory acute leukemia, and it could be recommended as therapeutic options prior to HSCT [ 16 – 22 ]. The introduction of FLAG and CLAG with IDA /Mito into the conditioning regimen is undoubtedly beneficial to the elimination of residual leukemia with acceptable toxicity, which is one of the main factors to reduce the recurrence .…”

Efficacy of cytarabine, aclarubicin and granulocyte colony-stimulating factor (CAG) regimen compared to FLAG regimen for adult patients with relapsed/refractory Philadelphia chromosome-negative acute lymphoblastic leukemia

“…High dose Ara-C combined with other regimens are available, such as FLAG, FLAG-IDA etc [16,22]. FLAG is commonly used salvage regimen which is believed to produce a CR rate ranging from 39.1-83%, yet followed by severe myelosuppression and related infection [8,23]. For resistant and relapsed patients, some clinical center applied FLAG-IDA regimen, which combined idarubicin with FLAG regimen, while the CR rate ranges from 20-42% and the side effect including pancytopenia, life-threatening infections and neurological toxicity are observed [24,25].…”

Advances in the drug therapies of acute myeloid leukemia (except acute promyelocytic leukemia)

“…Major complications encountered were anemia, fever, bleeding, mucositis, and bacterial infections. 41 …”