The level of residual disease based on mutant NPM1 is an independent prognostic factor for relapse and survival in AML

被引:164
作者
Shayegi, Nona [1 ]
Kramer, Michael [1 ]
Bornhaeuser, Martin [1 ]
Schaich, Markus [1 ]
Schetelig, Johannes [1 ]
Platzbecker, Uwe [1 ]
Roellig, Christoph [1 ]
Heiderich, Caroline [2 ]
Landt, Olfert [3 ]
Ehninger, Gerhard [1 ]
Thiede, Christian [1 ]
机构
[1] Tech Univ Dresden, Univ Klinikum Carl Gustav Carus, Med Klin & Poliklin 1, D-01307 Dresden, Germany
[2] AgenDix GmbH, Dresden, Germany
[3] TIB MOLBIOL Synth Lab GmbH, Berlin, Germany
关键词
ACUTE MYELOID-LEUKEMIA; ACUTE MYELOGENOUS LEUKEMIA; POLYMERASE-CHAIN-REACTION; CYTOPLASMIC NUCLEOPHOSMIN; GENE-MUTATIONS; ADULT PATIENTS; ABNORMALITIES; DIAGNOSIS; FLT3;
D O I
10.1182/blood-2012-10-461749
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Mutations of the NPM1 gene (NPM1(mut)) are among the most common genetic alterations in acute myeloid leukemia and are suitable for minimal residual disease detection. We retrospectively investigated the prognostic impact of NPM1(mut)-based minimal residual disease detection from bone marrow for development of relapse by using a newly developed real-time polymerase chain reaction based on locked nucleic acid-containing primers in 174 patients, 155 of whom were treated within prospective protocols. The prognostic value of 5 cutoff values after completion of treatment or after allogeneic transplantation was studied by using cause-specific hazard models. Subsequent validation using cross-validated partial likelihood analysis revealed that an increase of more than 1% NPM1(mut)/ABL1 was most prognostic for relapse after chemotherapy, whereas an increase of more than 10% NPM1(mut)/ABL1 was most prognostic for relapse after allogeneic transplantation. Univariate and multivariate analysis of disease-free survival and overall survival revealed a significantly worse outcome in patients with >1% NPM1(mut)/ABL1 and >10% NPM1(mut)/ABL1, respectively, which remained significant after adjustment for FLT3-internal tandem duplication status. Our results in a large data set define and optimize cutoff values for early diagnosis of molecular relapse. These results may be especially important for defining triggers for early therapeutic intervention.
引用
收藏
页码:83 / 92
页数:10
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