Rothenberg-Thurley, Maja and Amler, Susanne and Goerlich, Dennis and Koehnke, Thomas and Konstandin, Nikola P. and Schneider, Stephanie and Sauerland, Maria C. and Herold, Tobias and Hubmann, Max and Ksienzyk, Bianka and Zellmeier, Evelyn and Bohlander, Stefan K. and Subklewe, Marion and Faldum, Andreas and Hiddemann, Wolfgang and Braess, Jan and Spiekermann, Karsten and Metzeler, Klaus H. (2018) Persistence of pre-leukemic clones during first remission and risk of relapse in acute myeloid leukemia. LEUKEMIA, 32 (7). pp. 1598-1608. ISSN 0887-6924, 1476-5551
Full text not available from this repository. (Request a copy)Abstract
Some patients with acute myeloid leukemia (AML) who are in complete remission after induction chemotherapy harbor persisting pre-leukemic clones, carrying a subset of leukemia-associated somatic mutations. There is conflicting evidence on the prognostic relevance of these clones for AML relapse. Here, we characterized paired pre-treatment and remission samples from 126 AML patients for mutations in 68 leukemia-associated genes. Fifty patients (40%) retained >= 1 mutation during remission at a VAF of >= 2%. Mutation persistence was most frequent in DNMT3A (65% of patients with mutations at diagnosis), SRSF2 (64%), TET2 (55%), and ASXL1 (46%), and significantly associated with older age (p < 0.0001) and, in multivariate analyses adjusting for age, genetic risk, and allogeneic transplantation, with inferior relapse-free survival (hazard ratio (HR), 2.34; p = 0.0039) and overall survival (HR, 2.14; p = 0.036). Patients with persisting mutations had a higher cumulative incidence of relapse before, but not after allogeneic stem cell transplantation. Our work underlines the relevance of mutation persistence during first remission as a novel risk factor in AML. Persistence of pre-leukemic clones may contribute to the inferior outcome of elderly AML patients. Allogeneic transplantation abrogated the increased relapse risk associated with persisting pre-leukemic clones, suggesting that mutation persistence may guide post-remission treatment.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | MINIMAL RESIDUAL DISEASE; DNMT3A MUTATIONS; GENE-MUTATIONS; RECOMMENDATIONS; IDENTIFICATION; INDUCTION; DIAGNOSIS; OUTCOMES; AML; |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 06 Mar 2020 08:08 |
| Last Modified: | 06 Mar 2020 08:08 |
| URI: | https://pred.uni-regensburg.de/id/eprint/14288 |
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