Persistence of pre-leukemic clones during first remission and risk of relapse in acute myeloid leukemia

Rothenberg-Thurley, Maja; Amler, Susanne; Goerlich, Dennis; Köhnke, Thomas; Konstandin, Nikola P.; Schneider, Stephanie; Sauerland, Maria C.; Herold, Tobias; Hubmann, Max; Ksienzyk, Bianka; Zellmeier, Evelyn; Bohlander, Stefan K.; Subklewe, Marion; Faldum, Andreas; Hiddemann, Wolfgang; Braess, Jan; Spiekermann, Karsten und Metzeler, Klaus H. (2018): Persistence of pre-leukemic clones during first remission and risk of relapse in acute myeloid leukemia. In: Leukemia, Bd. 32, Nr. 7: S. 1598-1608

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.

• Dokumententyp: Zeitschriftenartikel
• Fakultät: Medizin
• Themengebiete: 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit
• ISSN: 0887-6924
• Sprache: Englisch