Clinical Outcomes in Patients with Relapsed/Refractory Acute Leukemia Treated with FLAG-IDA Regimen.

Background: Patients with Refractory/Relapsed (R/R) acute leukemia (AL) have a poor prognosis. Objective: We aimed to evaluate the chemotherapy regimen fludarabine, cytarabine, granulocyte colony-stimulating factor, and idarubicin (FLAG-IDA) in patients with R/R AL. Patients: We studied 16 patients with R/R AL (five female; eleven male). Distribution of the AL subtype was: lymphoblastic n=5 (31%), myeloblastic n=10 (62%) and bifenotipic n=1 (7%). The median of time from diagnosis to the beginning of FLAG-IDA was 320 days. Indication of FLAG-IDA was as follows: relapsed (n=12), refractory (n=2) and consolidation after relapsed (n=1) or refractory (n=1). Before administering FLAG-IDA, six patients were in their first relapse after conventional chemotherapy and six patients had received at least two different chemotherapy protocols (anti-CD33 monoclonal antibody was combined with chemotherapy in 3 of these patients). Two patients were in relapse after autologous peripheral stem cell transplantation and two after related allogeneic bone marrow transplantation. Results: At the beginning of FLAG-IDA, the median age was 29.6 years old (range 11–56) and 5 out of 16 patients (31.2%) had a performance status of ≥2. All patients had at least one episode of febrile neutropenia in a median of 8.5 days (range 3–17) with positive blood cultures in 50% of the events. Grade 5 toxicity occurred in 4 patients resulting in a mortality of 25%. All of the deaths were due to sepsis. In patients with hematological recovery the median time to neutrophils recovery (> 0.5 × 109/l) was 26.5 days (range 17–38); platelet levels of more than 20 × 109/l and 50 × 109/l were reached in a median time of 28 (range 23–44) and 31 days (range 25–51), respectively. Complete remission (CR) was achieved in 7 cases (43%). In the univariate analysis factors significantly associated with CR were the level of hemoglobin in day 0 (CR 10.2 g/dl versus non-CR 7.7 g/dl; p=0.03) and a desfavorable prognostic karyotype at the diagnosis of AL (CR 1/6 versus 5/5 non-CR; p=0.013). After CR, five patients underwent allogeneic transplantation and two patients received a second course of FLAG-IDA. Six out of seven patients (85.7%) who achieved CR with FLAG-IDA relapsed at a median of 248 days (95% CI 22.17 to 473.82 days). Overall survival after FLAG-IDA in the surviving cohort had a median of 131 days (95% CI 121 a 565 days) and one year-survival was 35.71%. We found a significantly better overall survival in patients who received allogeneic transplantation post-FLAG-IDA than those who did not (median 694 vs. 121 days; HR 0.24; 95% CI 0.06 to 0.98; p=0.0157). Conclusions: In our series, FLAG-IDA demonstrated to be an effective salvage chemotherapy regimen but with a high rate of treatment-related deaths probably related to bad performance status. We found that the benefit in survival of this rescue treatment was restrained to patients who underwent allogeneic transplantation.