Measurable residual disease (MRD) monitoring by next-generation sequencing before allogeneic hematopoietic cell transplantation in AML

• Published in: Blood 2018-09, Vol.132 (16), p.1703-1713
• Main Authors: Thol, Felicitas, Gabdoulline, Razif, Liebich, Alessandro, Klement, Piroska, Schiller, Johannes, Kandziora, Christian, Hambach, Lothar, Stadler, Michael, Koenecke, Christian, Flintrop, Madita, Pankratz, Mira, Wichmann, Martin, Neziri, Blerina, Büttner, Konstantin, Heida, Bennet, Klesse, Sabrina, Chaturvedi, Anuhar, Kloos, Arnold, Göhring, Gudrun, Schlegelberger, Brigitte, Gaidzik, Verena I., Bullinger, Lars, Fiedler, Walter, Heim, Albert, Hamwi, Iyas, Eder, Matthias, Krauter, Jürgen, Schlenk, Richard F., Paschka, Peter, Döhner, Konstanze, Döhner, Hartmut, Ganser, Arnold, Heuser, Michael
• Format: Article
• Language: English
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2018-02-829911

Molecular measurable residual disease (MRD) assessment is not established in approximately 60 percent of acute myeloid leukemia (AML) patients due to the lack of suitable markers for quantitative real-time PCR. To overcome this limitation we established an error-corrected next-generation-sequencing (NGS) MRD approach which can be applied to any somatic gene mutation. The clinical significance of this approach was evaluated in 116 AML patients undergoing allogeneic hematopoietic cell transplantation (alloHCT) in complete morphologic remission (CR). Targeted resequencing at the time of diagnosis identified a suitable mutation in 93 percent of the patients covering 24 different genes. MRD was measured in CR samples from peripheral blood or bone marrow before alloHCT and identified 12 patients with persistence of an ancestral clone (variant allele frequency, VAF >5%). The remaining 96 patients formed the final cohort of which 45% were MRD positive (median VAF 0.33, range 0.016-4.91%). In competing risk analysis cumulative incidence of relapse (CIR) was higher in MRD positive than negative patients (HR 5.58, P