Fludarabine, cytarabine, and G-CSF (FLAG) for the treatment of poor risk acute myeloid leukemia

Abstract

Thirty-eight patients with primary resistant or relapsing acute myeloid leukemia (AML) were treated with fludarabine, cytarabine and granulocyte colony-stimulating factor (FLAG). Median age was 41 (range 11-70). Sixteen patients had AML that was primary resistant to induction treatment, while 22 were relapsed, 11 after autologous bone marrow transplant (AuBMT), 8 less than 6 months from complete remission (CR) achievement, and 3 were second relapse from chemotherapy alone. Overall, 21 of 38 patients (55%) obtained CR. Age, sex, length of CR, and interval between autoBMT and FLAG administration did not significantly influence the CR rate. On the contrary, a normal karyotype at diagnosis was significantly related to a better outcome. There were 4 induction deaths (10%), due to fungal infection in 2 patients and hemorrhagic complications in the remaining two. All patients experienced profound cytopenia. Median time to neutrophil (>500/microl) recovery was 21 days, while a platelet count >20,000/microl was reached after 23 days. The median period of hospitalization was 31 days. The nonhematological toxicity was mild, mainly consisting of mucositis. There were 17 documented infections and 17 episodes of fever of unknown origin. Following CR achievement, 6 patients received autoBMT, 3 alloBMT, 2 high-dose arabinosil-cytosine, and 2 are on a waiting list for transplantation procedure. We conclude that FLAG is an effective and well-tolerated regimen for refractory or recurrent AML, mainly useful for patients to be admitted to bone marrow transplantation.

Cell proliferation is related to in vitro drug resistance in childhood acute leukaemia

“…Several studies have indeed demonstrated that the in vitro sensitivity to cytarabine of AML cells could be enhanced by preincubation with granulocyte colony-stimulating factor (G-CSF) and/or with granulocyte -macrophage colony-stimulating factor (GM-CSF) (Butturini et al, 1990;Bai et al, 1999). Clinically, pretreatment with G-CSF (as in the FLAG regimen, which is a combination therapy of fludarabine, cytarabine, and G-CSF), seems to be effective and well tolerated in the treatment of poorrisk AML patients (Montillo et al, 1998;Jackson et al, 2001). The efficacy of this therapy, however, has not yet been determined in a controlled, randomised clinical study.…”

Analysis of feasibility of myeloablative therapy and autologous peripheral stem cell (PBSC) transplantation in the elderly: an interim report

“…Table 1 summarizes the principal clinical and diagnostic data of patients. The Table 1 Principal clinical characteristics of patients older than 60 years who underwent PBSC autotransplant following myeloablative therapy 16 for multiple myeloma, FLAG 17 at reduced dose for AML, the GIMEMA protocol for ALL or byphenotypic leukemia 18 and a combination of cisplatinum and vinorelbin for lung carcinoma. Patient status at PBSC autotransplant was relapse for eight patients (seven lymphomas, one myeloma), resistance for eight patients (two lymphomas, four myelomas, one carcinoma and one Waldenstrom's disease), complete remission for three patients (two leukemias and one myeloma).…”

Multivariate analysis of prognostic factors in patients with refractory and relapsed acute myeloid leukemia undergoing sequential high-dose cytosine arabinoside and mitoxantrone (S-HAM) salvage therapy: relevance of cytogenetic abnormalities

“…[32][33][34][35][36][37][38][39][40][41][42] Thus, on the basis of the current analyses, the assignment of salvage regimens to patients with refractory and relapsed AML should be stratified not only with regard to the duration of the first CR but also with regard to chromosome abnormalities. Further patients should be evaluated to add to the current data and also to clarify the role of chromosome abnormalities determined directly prior to salvage therapy which are different to the initial karyotype in about 60% of cases.…”