Treatment of “Poor Risk” Acute Myeloid Leukemia with Fludarabine, Cytarabine and G-CSF (Flag Regimen): A Single Center Study

Abstract

We describe a single center experience of 41 consecutive patients with poor prognosis acute myeloid leukemia (AML) who received a single course of FLAG regimen consisting of Fludarabine 30 mg/m2/day plus Cytarabine 2 gr/m2/day (days 1-5) and G-CSF 5 mg/Kg/day (from day 0 to polymorphonuclear recovery) as salvage therapy. Eleven patients were primarily refractory to previous chemotherapy, 10 patients were in first relapse, 2 patients in second relapse and 7 patients in relapse after transplants. Eleven cases were defined as secondary AML (diagnosis of AML made after a preexisting diagnosis of myelodysplastic syndrome). The median age was 52.6 years (range 16-72); 29 patients were males and 12 females. Overall, 23 (56%) patients reached complete remission (CR), 3 patients died of infection (2) or hemorrhage (1) during induction, and 15 (36%) patients had resistant disease. The highest CR rates (80%) were obtained in relapsed cases; de novo and secondary AML registered 60% and 45% of CR rates, respectively. Patients achieving CR received a second FLAG course as consolidation and were submitted to an individualized program post-remission therapy, depending on the age and performance status. Hematological and non hematological toxicities were acceptable. In conclusion, our data confirm that FLAG is a an high effective treatment for poor prognosis AML and in young patients allows intensive post remissional therapy including allogeneic BMT.

Combination Treatment of Flag with Non-Pegylated Liposomal Doxorubicin (MYOCET™) in Elderly Patients with Acute Myeloid Leukemia: A Single Center Experience

“…Hematological recovery was evaluated only in patients achieving CR: median time to reach neutrophils >1OOOIIlL and PLTs >20,0001IlL was 18 days (range 10-27) and 25 days (range 13-28), respectively. Mean duration ofG-CSF administration was 22 days (range [14][15][16][17][18][19][20][21][22][23][24]. Supportive treatment consisted ofa mean of9 packed red cell units (range 2-18) and 8 PLT units (range [3][4][5][6][7][8][9][10][11][12][13][14][15].…”

“…The combination of fludarabine, cytarabine, and granulocyte colony-stimulating factor (G-CSF) (FLAG) +/-anthracyclines has been reported to be effective and well tolerated in newly diagnosed patients with AML as well as in patients with poor risk AML (14)(15)(16)(17).…”

Cyclophosphamide combined with mitoxantrone and cytarabine is an effective salvage regimen for patients with acute myeloid leukemia who experienced primary induction failure or relapse

“…The majority of patients with CR relapsed within 1-2 years and the chance of long-term disease-free survival for relapsed patients is <10% (2). For the majority of relapsed patients, regimens involving fludarabine have been performed in previous studies for treatment, with a CR rate ranging between 30 and 60% (3)(4)(5)(6)(7)(8). Liso et al (9) and Kern et al (10) have also reported a high-dose of cytarabine, combined with mitoxantrone and etoposide, as a salvage regimen.…”

Sequential continuous infusion of fludarabine and cytarabine associated with liposomal daunorubicin (DaunoXome®) (FLAD) in primary refractory or relapsed adult acute myeloid leukemia patients

“…Recent evidences suggest that fludarabine acts synergistically with cytarabine to increase intracellular Ara-CTP, if given soon before or simultaneously with cytarabine [8][9][10]. Such regimens (FLAG, Flag-Ida, FLANG) have been employed in several studies for treating AML in elderly patients and in those with a poor-risk disease, with CR rate ranging from 30% to 60% [11][12][13][14][15][16][17]. Unfortunately, toxicity is often relevant, and response duration is usually short, precluding most patients from benefiting of a transplant procedure.…”