Randomized trial comparing standard vs sequential high-dose chemotherapy for inducing early CR in adult AML

Abstract

Here we evaluated whether sequential high-dose chemotherapy (sHD) increased the early complete remission (CR) rate in acute myelogenous leukemia (AML) compared with standard-intensity idarubicin-cytarabine-etoposide (ICE) chemotherapy. This study enrolled 574 patients (age, 16-73 years; median, 52 years) who were randomly assigned to ICE (n = 286 evaluable) or sHD (2 weekly 3-day blocks with cytarabine 2 g/m2 twice a day for 2 days plus idarubicin; n = 286 evaluable). Responsive patients were risk-stratified for a second randomization. Standard-risk patients received autograft or repetitive blood stem cell-supported high-dose courses. High-risk patients (and standard-risk patients not mobilizing stem cells) underwent allotransplantation. CR rates after 2 induction courses were comparable between ICE (80.8%) and sHD (83.6%; P = .38). sHD yielded a higher single-induction CR rate (69.2% vs 81.5%; P = .0007) with lower resistance risk (P < .0001), comparable mortality (P = .39), and improved 5-year overall survival (39% vs 49%; P = .045) and relapse-free survival (36% vs 48%; P = .028), despite greater hematotoxicity delaying or reducing consolidation blocks. sHD improved the early CR rate in high-risk AML (odds ratio, 0.48; 95% confidence interval [CI], 0.31-0.74; P = .0008) and in patients aged 60 years and less with de novo AML (odds ratio, 0.46; 95% CI, 0.27-0.78; P = .003), and also improved overall/relapse-free survival in the latter group (hazard ratio, 0.70; 95% CI, 0.52-0.94; P = .01), in standard-risk AML, and postallograft (hazard ratio, 0.61; 95% CI, 0.39-0.96; P = .03). sHD was feasible, effectively achieved rapid CR, and improved outcomes in AML subsets. This study is registered at www.clinicaltrials.gov as #NCT00495287.

High Throughput Molecular Characterization of Normal Karyotype Acute Myeloid Leukemia in the Context of the Prospective Trial 02/06 of the Northern Italy Leukemia Group (NILG)

“…In this context, the purpose of this study was to define the association of molecular mutations with the outcome of a cohort of 221 NK-AML patients treated according to a prospective trial comparing a standard vs. high-dose chemotherapy regimen for remission induction (ClinicalTrials.gov identifier: NCT00495287) [12].…”

Early peripheral blast cell clearance predicts minimal residual disease status and refines disease prognosis in acute myeloid leukemia

“…Complete remission (CR), non‐responsive disease (NR), early induction death (ED), disease‐free survival (DFS), and overall survival (OS) were defined according to standard criteria 27 . For risk definition, patients were stratified according to the original NILG study design 26 and the European Leukemia Net (ELN) 2010 system in post hoc analysis 28 …”

Clinical significance of chromatin-spliceosome acute myeloid leukemia: a report from the Northern Italy Leukemia Group (NILG) randomized trial 02/06

“…The NILG-AML 02/06 multicentric Italian trial (17) enrolled 574 patients with newly diagnosed AML [≥20% bone marrow (BM) blasts] or high-risk MDS (10)(11)(12)(13)(14)(15)(16)(17)(18)(19) between 2007 and 2012. All participants were randomized to receive induction with standard-dose idarubicin, cytarabine and etoposide (ICE) or high-dose cytarabine and idarubicin (sHD).…”

“…Patients not responding to first induction underwent an intensified re-induction with sHD. A consolidative alloHSCT was performed in highrisk patients based on study-specific risk stratification, as previously reported (17). Written informed consent for inclusion in the clinical trial and genetic analyses was provided by all patients.…”

“…To investigate the clinical significance of the CS mutational signature, we re-assessed patients' diagnosis according to the presence of CS mutations in a large cohort of newly diagnosed AML patients enrolled into a prospective trial (NILG AML 02/06) [ClinicalTrials.gov Identifier: NCT00495287] (17). In this study, we report the characteristics and outcomes of initially defined de novo AML patients carrying CS mutations as compared with other clinically defined de novo AML patients without CS mutations and patients with sAML defined by standard WHO criteria.…”