Phase-II trial of idarubicin, fludarabine, cytosine arabinoside, and filgrastim (Ida-FLAG) for treatment of refractory, relapsed, and secondary AML

Abstract

The current phase-II trial was initiated to assess the efficacy and toxicity of the Ida-FLAG regimen in patients with poor-risk acute myeloid leukemia (AML). Three subgroups of patients with AML were eligible for the study: (a) refractory, (b) first relapse, or (c) secondary AML (i.e., signs of trilineage myelodysplasia at diagnosis or the history of a myelodysplasia or myeloproliferative disorder). Fifty-seven fully evaluable patients were included in the study. Twenty patients received a second course of Ida-FLAG. Complete remission was achieved by 1/14 patients with refractory AML, 12/15 patients with relapsed AML, and 17/28 patients with secondary AML. The median duration of ANC <1000/microl was 17 days (10-36); of platelets <30,000/microl 23 days (9-65); of days with fever >38.0 degrees C 6 days (1-33). Thirteen patients (22.8%) died within 42 days of severe infection or hemorrhage. Overall survival at 20 weeks in the subgroups was 24% for patients with refractory, 78% for patients with relapsed, and 55% for patients with secondary AML. The toxicity of the first cycle of Ida-FLAG is moderate. The feasibility and subjective tolerance of the Ida-FLAG regimen are acceptable. There is no evidence for an increase of atypical infections. The efficacy for patients with secondary AML and especially those with first relapse of AML is good, with a high rate of complete remissions. Remission duration seems to be short. Therefore, an intensified post-remission therapy seems necessary.

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

“…FLT3 (ITD/TKD) was the only statistically significant factor affecting CR, while different cytogenetic risk groups revealed no influence on the treatment results. The result was similar to the observation made by others (20)(21). The prognosis of adult patients with AML resistant to first-line or relapsed following CR1 within <6 months duration is poor.…”

Fludarabine and cytosine are less effective than standard ADE chemotherapy in high-risk acute myeloid leukemia, and addition of G-CSF and ATRA are not beneficial: results of the MRC AML-HR randomized trial

“…[17][18][19][20][21][22][23][24][25][26] This has led to widespread adoption of such schedules. Our study does not support For ATRA, the number of patients randomly assigned to the group was 180; for no ATRA, it was 182.…”

“…17 A number of phase 2 studies have now been published on the combination of FLAG Ϯ idarubicin to treat relapsed or refractory AML, high-risk myelodysplasia, and acute lymphoblastic leukemia in relapse. [17][18][19][20][21][22][23][24][25][26] Remission rates vary from 50% to 60% and the median duration of remission from 4 to 12 months. It is impossible to ascertain whether the addition of an anthracycline is advantageous.…”

Graft-versus-tumour effect in refractory metastatic neuroblastoma

“…sAML occurring in a patient treated for recurrent cancer also has an extremely bad prognosis. The long-term disappearance of leukaemic cells in our patient cannot be explained solely by the drugs used, 6,7 and probably relies on the graftversus-leukaemia (GVL) potential of allogeneic BMT. Hence, to our knowledge, it is the first report of simultaneous GVL and graft-versus-tumour after RIC allogeneic BMT, showing clearly the graft-versus-malignancy potential of allogeneic BMT following attenuated regimen.…”