Prognostic significance of deep sequencing for analysis of measurable residual disease in acute myeloid leukemia with mutation.
Sofie Johansson Alm, Gustav Orrsj��, Giti Shah Barkhordar, Anna Rehammar, Anna Staffas, Erik Delsing Malmberg, Per-Ola Andersson, Hege Garelius, Mats Hardling, Lars Palmqvist, Linda Fogelstrand
Author Information
Sofie Johansson Alm: Department of Laboratory Medicine, Institute of Biomedicine, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden. ORCID
Gustav Orrsj��: Department of Laboratory Medicine, Institute of Biomedicine, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden.
Giti Shah Barkhordar: Department of Clinical Genetics and Genomics, Sahlgrenska University Hospital, Region Vastra Gotaland, Gothenburg, Sweden.
Anna Rehammar: School of Public Health and Community Medicine, Institute of Medicine, University of Gothenburg, Gothenburg, Sweden.
Anna Staffas: Department of Laboratory Medicine, Institute of Biomedicine, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden.
Erik Delsing Malmberg: Department of Clinical Pathology, Sahlgrenska University Hospital, Region Vastra Gotaland, Gothenburg, Sweden.
Per-Ola Andersson: Section of Hematology and Coagulation, Sahlgrenska University Hospital, Region Vastra Gotaland, Gothenburg, Sweden. ORCID
Hege Garelius: Section of Hematology and Coagulation, Sahlgrenska University Hospital, Region Vastra Gotaland, Gothenburg, Sweden.
Mats Hardling: Department of Haematology, NU Hospital Group, Region Vastra Gotaland, Uddevalla, Sweden.
Lars Palmqvist: Department of Laboratory Medicine, Institute of Biomedicine, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden.
Linda Fogelstrand: Department of Laboratory Medicine, Institute of Biomedicine, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden.
In acute myeloid leukemia with mutation, analysis of measurable residual disease (MRD) with reverse transcription quantitative polymerase chain reaction (RT-qPCR) is recommended for response assessment and monitoring after treatment. For rare mutations in , this is not readily available. Therefore, we evaluated the prognostic value of deep sequencing covering all exon 11 variants, using retrospectively analyzed bone marrow samples from 97 patients in remission during treatment. MRD positivity was defined as mutation at ���0.05% variant allele frequency based on a previous comparison with RT-qPCR. Deep sequencing MRD positivity at any time during consolidation predicted relapse-free survival (at 3 years: 23.1��������11.7% vs. 70.8��������6.1%, ���<���0.001) and overall survival (at 3 years: 30.8��������12.8% vs. 63.8��������6.6%, ���=���0.014). In multivariable analysis, MRD status during consolidation was the sole predictor for relapse. In conclusion, deep sequencing of has high prognostic value and extends MRD monitoring to patients with rare mutations in .
