Daniel Steinbach1, Peter Bader2, Andre Willasch2, Stephan Bartholomae3, Klaus-Michael Debatin3, Martin Zimmermann4, Ursula Creutzig4, Dirk Reinhardt4, Bernd Gruhn5.
Abstract
PURPOSE: This study evaluated the prognostic impact of a novel, simple, and standardized assay for monitoring minimal residual disease (MRD) in pediatric acute myelogenous leukemia (AML). EXPERIMENTAL
DESIGN: The expression of seven leukemia-associated genes (WT1, PRAME, CCL23, GAGED2, MSLN, SPAG6, and ST18) was measured by TaqMan Low Density Arrays in 112 patients and 52 healthy controls. Patients were treated according to the multicenter study AML-BFM 2004. Samples were collected prospectively at standard time points. The laboratory that measured MRD was blinded to patient outcome.
RESULTS: Relapse-free survival (RFS) was 95% (N = 19; SE = 5%) if expression of all genes was down to normal on day 15, 63% (N = 41; SE = 8%) if expression was normalized on day 28, and 38% (N = 21; SE = 11%) in patients who still showed elevated expression on day 28. The prognostic impact of MRD remained significant (P = 0.002) when patients were stratified for the AML-BFM 2004 risk group. Multivariate analysis identified the MRD risk group and day 28 cytology as the only independent prognostic factors. Patients with a cytologic nonremission on day 28, which was confirmed by MRD, had a dismal prognosis. Only 1 out of 8 patients survived without relapse.
CONCLUSIONS: This novel method of monitoring MRD has a strong prognostic impact that is independent from established risk factors in childhood AML. ©2014 American Association for Cancer Research.
PURPOSE: This study evaluated the prognostic impact of a novel, simple, and standardized assay for monitoring minimal residual disease (MRD) in pediatric acute myelogenous leukemia (AML). EXPERIMENTAL
DESIGN: The expression of seven leukemia-associated genes (WT1, PRAME, CCL23, GAGED2, MSLN, SPAG6, and ST18) was measured by TaqMan Low Density Arrays in 112 patients and 52 healthy controls. Patients were treated according to the multicenter study AML-BFM 2004. Samples were collected prospectively at standard time points. The laboratory that measured MRD was blinded to patient outcome.
RESULTS: Relapse-free survival (RFS) was 95% (N = 19; SE = 5%) if expression of all genes was down to normal on day 15, 63% (N = 41; SE = 8%) if expression was normalized on day 28, and 38% (N = 21; SE = 11%) in patients who still showed elevated expression on day 28. The prognostic impact of MRD remained significant (P = 0.002) when patients were stratified for the AML-BFM 2004 risk group. Multivariate analysis identified the MRD risk group and day 28 cytology as the only independent prognostic factors. Patients with a cytologic nonremission on day 28, which was confirmed by MRD, had a dismal prognosis. Only 1 out of 8 patients survived without relapse.
CONCLUSIONS: This novel method of monitoring MRD has a strong prognostic impact that is independent from established risk factors in childhood AML. ©2014 American Association for Cancer Research.
Entities:
Mesh：
Year: 2014
PMID： 25501127 DOI： 10.1158/1078-0432.CCR-14-1999
Source DB: PubMed Journal: Clin Cancer Res ISSN： 1078-0432 Impact factor: 12.531