Continuous sequential infusion of fludarabine and cytarabine for elderly patients with acute myeloid leukaemia secondary to a previously diagnosed myelodysplastic syndrome

Abstract

Acute myeloid leukaemia (AML) secondary to myelodysplastic syndrome (MDS) is characterized by poor prognosis, namely in older patients. The combination of fludarabine (F) with cytarabine (ARA-C) ± G-CSF was proven as effective in patients with poor risk AML. The efficacy and toxicity of a regimen including F + ARA-C as sequential continuous infusion (CI-FLA) in 64 untreated patients aged >60 years, in which AML arose after a previous MDS, was investigated. Median age was 67 years (61-81). In patients achieving CR, an additional course, followed by G-CSF to mobilize CD34+ cells and subsequent autologous stem cell transplantation (ASCT) were programmed. Overall, 43 patients (67%) achieved complete remission (CR). There were 10 induction deaths (16%), while 11 patients (17%) were refractory to induction treatment. Thirty-four patients (79% of remitters) were eligible for the consolidation and 30 were monitorized for the mobilization of CD34+ cells, collection being successful in 20 of them (67%). Median number of CD34+ cells/kg collected was 6.8 × 10E6. Thirteen patients (20% of the whole population) received ASCT. Median disease free survival (DFS) and overall survival (OS) were 10 and 9 months, respectively. Survival at 5 years is projected to 15%. The only parameter significantly related to either DFS duration or OS duration was unfavourable cytogenetics, which did significantly influence also CR achievement. CI-FLA is effective in elderly patients with AML secondary to previously diagnosed MDS. Best results are achievable in the subgroup of patients with diploid karyotype.

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

“…This response rate is similar to the 30–60% CR rates reported in most other studies in elderly AML patients receiving induction chemotherapy . Ferrara and colleagues evaluated the efficacy and toxicity of FLAG given as sequential continuous infusion in 64 untreated elderly AML patients aged >60 yr with secondary AML . Overall, 67% of patients achieved a CR, 17% of patients were refractory, and the mortality was 16%.…”

“… noted the median OS and disease‐free survival were each 10 months. In their more recent study of elderly patients, FLAG was associated with a median OS of 9 months . Both studies, however, excluded patients with severe organ dysfunction, including cardiac disease with LVEF <40%, and included autologous SCT as a potential postinduction therapy for eligible patients.…”

Is There Still a Role for Autologous Stem Cell Transplantation for the Treatment of Acute Myeloid Leukemia?

“…In a retrospective series of 40 patients, we previously demonstrated that age has no influence on PBSC mobilization and collection in AML; in most patients, PBSCs were collected after consolidation based on continuous sequential infusion of fludarabine and ARAC, followed by granulocyte-colony-stimulating factor with a successful rate over 90% [65]. Overall, results in terms of survival after conditioning with Bu and Ida were promising either in de novo or secondary disease, but relapse rate in patients with unfavorable cytogenetics was impressively high [66]. In patients with mobilization failure, harvesting HSCs from bone marrow could be considered, but in our own experience, it is poorly accepted by patients and associated with different inconveniences; therefore, we do not currently consider bone marrow harvesting, and, in the case of no or insufficient mobilization, we administer one further course of IDARAC.…”