TY - JOUR
T1 - Postinduction minimal residual disease predicts outcome and benefit from allogeneic stem cell transplantation in acute myeloid leukemia with NPM1 mutation
T2 - A study by the acute leukemia French association group
AU - Balsat, Marie
AU - Renneville, Aline
AU - Thomas, Xavier
AU - De Botton, Stéphane
AU - Caillot, Denis
AU - Marceau, Alice
AU - Lemasle, Emilie
AU - Marolleau, Jean Pierre
AU - Nibourel, Olivier
AU - Berthon, Céline
AU - Raffoux, Emmanuel
AU - Pigneux, Arnaud
AU - Rodriguez, Céline
AU - Vey, Norbert
AU - Cayuela, Jean Michel
AU - Hayette, Sandrine
AU - Braun, Thorsten
AU - Coudé, Marie Magdeleine
AU - Terre, Christine
AU - Celli-Lebras, Karine
AU - Dombret, Hervé
AU - Preudhomme, Claude
AU - Boissel, Nicolas
N1 - Publisher Copyright:
© 2016 by American Society of Clinical Oncology.
PY - 2017/1/10
Y1 - 2017/1/10
N2 - Purpose This study assessed the prognostic impact of postinduction NPM1-mutated (NPM1m) minimal residual disease (MRD) in young adult patients (age, 18 to 60 years) with acute myeloid leukemia, and addressed the question of whether NPM1m MRD may be used as a predictive factor of allogeneic stem cell transplantation (ASCT) benefit. Patients and Methods Among 229 patients with NPM1m who were treated in the Acute Leukemia French Association 0702 (ALFA-0702) trial, MRD evaluation was available in 152 patients in first remission. Patients with nonfavorable AML according to the European LeukemiaNet (ELN) classification were eligible for ASCT in first remission. Results After induction therapy, patients who did not achieve a 4-log reduction in NPM1m peripheral blood-MRD (PB-MRD) had a higher cumulative incidence of relapse (subhazard ratio [SHR], 5.83; P <.001) and a shorter overall survival (OS; hazard ratio [HR], 10.99; P <.001). In multivariable analysis, an abnormal karyotype, the presence of FLT3-internal tandem duplication (ITD), and a < 4-log reduction in PB-MRD were significantly associated with a higher relapse incidence and shorter OS. In the subset of patients with FLT3-ITD, only age, white blood cell count, and < 4-log reduction in PB-MRD, but not FLT3-ITD allelic ratio, remained of significant prognostic value. In these patients with nonfavorable AML according to European LeukemiaNet, disease-free survival and OS were significantly improved by ASCT in those with a <4-log reduction in PB-MRD. This benefit was not observed in those with a < 4-log reduction in PB-MRD, with a significant interaction between ASCT effect and PB-MRD response (P = .024 and .027 for disease-free survival and OS, respectively). Conclusion Our study supports the strong prognostic significance of early NPM1mPB-MRD, independent of the cytogenetic and molecular context. Moreover, NPM1m PB-MRD may be used as a predictive factor for ASCT indication.
AB - Purpose This study assessed the prognostic impact of postinduction NPM1-mutated (NPM1m) minimal residual disease (MRD) in young adult patients (age, 18 to 60 years) with acute myeloid leukemia, and addressed the question of whether NPM1m MRD may be used as a predictive factor of allogeneic stem cell transplantation (ASCT) benefit. Patients and Methods Among 229 patients with NPM1m who were treated in the Acute Leukemia French Association 0702 (ALFA-0702) trial, MRD evaluation was available in 152 patients in first remission. Patients with nonfavorable AML according to the European LeukemiaNet (ELN) classification were eligible for ASCT in first remission. Results After induction therapy, patients who did not achieve a 4-log reduction in NPM1m peripheral blood-MRD (PB-MRD) had a higher cumulative incidence of relapse (subhazard ratio [SHR], 5.83; P <.001) and a shorter overall survival (OS; hazard ratio [HR], 10.99; P <.001). In multivariable analysis, an abnormal karyotype, the presence of FLT3-internal tandem duplication (ITD), and a < 4-log reduction in PB-MRD were significantly associated with a higher relapse incidence and shorter OS. In the subset of patients with FLT3-ITD, only age, white blood cell count, and < 4-log reduction in PB-MRD, but not FLT3-ITD allelic ratio, remained of significant prognostic value. In these patients with nonfavorable AML according to European LeukemiaNet, disease-free survival and OS were significantly improved by ASCT in those with a <4-log reduction in PB-MRD. This benefit was not observed in those with a < 4-log reduction in PB-MRD, with a significant interaction between ASCT effect and PB-MRD response (P = .024 and .027 for disease-free survival and OS, respectively). Conclusion Our study supports the strong prognostic significance of early NPM1mPB-MRD, independent of the cytogenetic and molecular context. Moreover, NPM1m PB-MRD may be used as a predictive factor for ASCT indication.
UR - http://www.scopus.com/inward/record.url?scp=85009918066&partnerID=8YFLogxK
U2 - 10.1200/JCO.2016.67.1875
DO - 10.1200/JCO.2016.67.1875
M3 - Article
C2 - 28056203
AN - SCOPUS:85009918066
SN - 0732-183X
VL - 35
SP - 185
EP - 193
JO - Journal of Clinical Oncology
JF - Journal of Clinical Oncology
IS - 2
ER -