Cell‐free DNA for detection and monitoring of extramedullary AML relapse
Abstract Isolated extramedullary manifestations (IEM) of acute myeloid leukemia (AML) are recurrent events, especially following allogeneic hematopoietic cell transplantation (alloHCT). To date, measurable residual disease (MRD) assessment for this difficult‐to‐treat patient cohort has not been esta...
Saved in:
| Main Authors: | , , , , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2025-03-01
|
| Series: | HemaSphere |
| Online Access: | https://doi.org/10.1002/hem3.70097 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849388009543172096 |
|---|---|
| author | Henri C. Hupe Clara P. Wienecke Stephan Bartels Elisa Schipper Jannika Leßmann Alina Lasch Maximilian Bader Razif Gabdoulline Martin Neugebohren Elke Dammann Hans H. Kreipe Ulrich Lehmann Anke K. Bergmann Nataliya Di Donato Michael Stadler Matthias Eder Arnold Ganser Florian H. Heidel Felicitas Thol Michael Heuser |
| author_facet | Henri C. Hupe Clara P. Wienecke Stephan Bartels Elisa Schipper Jannika Leßmann Alina Lasch Maximilian Bader Razif Gabdoulline Martin Neugebohren Elke Dammann Hans H. Kreipe Ulrich Lehmann Anke K. Bergmann Nataliya Di Donato Michael Stadler Matthias Eder Arnold Ganser Florian H. Heidel Felicitas Thol Michael Heuser |
| author_sort | Henri C. Hupe |
| collection | DOAJ |
| description | Abstract Isolated extramedullary manifestations (IEM) of acute myeloid leukemia (AML) are recurrent events, especially following allogeneic hematopoietic cell transplantation (alloHCT). To date, measurable residual disease (MRD) assessment for this difficult‐to‐treat patient cohort has not been established. In this study, we evaluated highly sensitive next‐generation sequencing (NGS) of IEM‐AML tumor and compared it with cell‐free DNA (cfDNA) from plasma, as well as highly sensitive NGS analysis of bone marrow mononuclear cells (BMMC) and peripheral blood mononuclear cells (PBMC), in a cohort of 15 IEM‐AML patients with 19 IEM‐AML episodes. cfDNA demonstrated a superior representation of IEM‐AML tumor mutations compared to BMMC or PBMC, with a median variant allele frequency (VAF) of 0.8% and a mutation detection rate of 62% (37 of 60 mutations), compared to a median VAF of 0.05% and detection rate of 27%, respectively (16 of 60 mutations, p < 0.01). Among 44 mutations identified in 14 IEM‐AML relapse tumors, 30 mutations (68%) were known from initial diagnosis. Using diagnostic mutations from initial diagnosis for MRD analysis and detection of IEM‐AML relapse, 16 of 17 IEM‐AML relapse episodes were detected via cfDNA, whereas only 7 of 17 were identified using conventional analysis of BMMC or PBMC. Our findings demonstrate that cfDNA analysis from plasma effectively captures the molecular profile of IEM‐AML. More than one‐third of clinically relevant mutations were exclusively detected through cfDNA and were missed by conventional NGS‐MRD of BMMC or PBMC. These results suggest that MRD monitoring using cfDNA offers a more comprehensive and sensitive approach to detecting IEM‐AML relapse compared to standard methods. |
| format | Article |
| id | doaj-art-a4f1a3a0fb2b44c0a5a5aa8e2f6da3aa |
| institution | Kabale University |
| issn | 2572-9241 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Wiley |
| record_format | Article |
| series | HemaSphere |
| spelling | doaj-art-a4f1a3a0fb2b44c0a5a5aa8e2f6da3aa2025-08-20T03:42:25ZengWileyHemaSphere2572-92412025-03-0193n/an/a10.1002/hem3.70097Cell‐free DNA for detection and monitoring of extramedullary AML relapseHenri C. Hupe0Clara P. Wienecke1Stephan Bartels2Elisa Schipper3Jannika Leßmann4Alina Lasch5Maximilian Bader6Razif Gabdoulline7Martin Neugebohren8Elke Dammann9Hans H. Kreipe10Ulrich Lehmann11Anke K. Bergmann12Nataliya Di Donato13Michael Stadler14Matthias Eder15Arnold Ganser16Florian H. Heidel17Felicitas Thol18Michael Heuser19Department of Hematology, Hemostasis, Oncology and Stem Cell Transplantation Hannover Medical School Hannover GermanyDepartment of Hematology, Hemostasis, Oncology and Stem Cell Transplantation Hannover Medical School Hannover GermanyInstitute of Pathology Hannover Medical School Hannover GermanyInstitute of Pathology Hannover Medical School Hannover GermanyDepartment of Hematology, Hemostasis, Oncology and Stem Cell Transplantation Hannover Medical School Hannover GermanyDepartment of Hematology, Hemostasis, Oncology and Stem Cell Transplantation Hannover Medical School Hannover GermanyDepartment of Hematology, Hemostasis, Oncology and Stem Cell Transplantation Hannover Medical School Hannover GermanyDepartment of Hematology, Hemostasis, Oncology and Stem Cell Transplantation Hannover Medical School Hannover GermanyDepartment of Hematology, Hemostasis, Oncology and Stem Cell Transplantation Hannover Medical School Hannover GermanyDepartment of Hematology, Hemostasis, Oncology and Stem Cell Transplantation Hannover Medical School Hannover GermanyInstitute of Pathology Hannover Medical School Hannover GermanyInstitute of Pathology Hannover Medical School Hannover GermanyDepartment of Human Genetics Hannover Medical School Hannover GermanyDepartment of Human Genetics Hannover Medical School Hannover GermanyDepartment of Hematology, Hemostasis, Oncology and Stem Cell Transplantation Hannover Medical School Hannover GermanyDepartment of Hematology, Hemostasis, Oncology and Stem Cell Transplantation Hannover Medical School Hannover GermanyDepartment of Hematology, Hemostasis, Oncology and Stem Cell Transplantation Hannover Medical School Hannover GermanyDepartment of Hematology, Hemostasis, Oncology and Stem Cell Transplantation Hannover Medical School Hannover GermanyDepartment of Hematology, Hemostasis, Oncology and Stem Cell Transplantation Hannover Medical School Hannover GermanyDepartment of Hematology, Hemostasis, Oncology and Stem Cell Transplantation Hannover Medical School Hannover GermanyAbstract Isolated extramedullary manifestations (IEM) of acute myeloid leukemia (AML) are recurrent events, especially following allogeneic hematopoietic cell transplantation (alloHCT). To date, measurable residual disease (MRD) assessment for this difficult‐to‐treat patient cohort has not been established. In this study, we evaluated highly sensitive next‐generation sequencing (NGS) of IEM‐AML tumor and compared it with cell‐free DNA (cfDNA) from plasma, as well as highly sensitive NGS analysis of bone marrow mononuclear cells (BMMC) and peripheral blood mononuclear cells (PBMC), in a cohort of 15 IEM‐AML patients with 19 IEM‐AML episodes. cfDNA demonstrated a superior representation of IEM‐AML tumor mutations compared to BMMC or PBMC, with a median variant allele frequency (VAF) of 0.8% and a mutation detection rate of 62% (37 of 60 mutations), compared to a median VAF of 0.05% and detection rate of 27%, respectively (16 of 60 mutations, p < 0.01). Among 44 mutations identified in 14 IEM‐AML relapse tumors, 30 mutations (68%) were known from initial diagnosis. Using diagnostic mutations from initial diagnosis for MRD analysis and detection of IEM‐AML relapse, 16 of 17 IEM‐AML relapse episodes were detected via cfDNA, whereas only 7 of 17 were identified using conventional analysis of BMMC or PBMC. Our findings demonstrate that cfDNA analysis from plasma effectively captures the molecular profile of IEM‐AML. More than one‐third of clinically relevant mutations were exclusively detected through cfDNA and were missed by conventional NGS‐MRD of BMMC or PBMC. These results suggest that MRD monitoring using cfDNA offers a more comprehensive and sensitive approach to detecting IEM‐AML relapse compared to standard methods.https://doi.org/10.1002/hem3.70097 |
| spellingShingle | Henri C. Hupe Clara P. Wienecke Stephan Bartels Elisa Schipper Jannika Leßmann Alina Lasch Maximilian Bader Razif Gabdoulline Martin Neugebohren Elke Dammann Hans H. Kreipe Ulrich Lehmann Anke K. Bergmann Nataliya Di Donato Michael Stadler Matthias Eder Arnold Ganser Florian H. Heidel Felicitas Thol Michael Heuser Cell‐free DNA for detection and monitoring of extramedullary AML relapse HemaSphere |
| title | Cell‐free DNA for detection and monitoring of extramedullary AML relapse |
| title_full | Cell‐free DNA for detection and monitoring of extramedullary AML relapse |
| title_fullStr | Cell‐free DNA for detection and monitoring of extramedullary AML relapse |
| title_full_unstemmed | Cell‐free DNA for detection and monitoring of extramedullary AML relapse |
| title_short | Cell‐free DNA for detection and monitoring of extramedullary AML relapse |
| title_sort | cell free dna for detection and monitoring of extramedullary aml relapse |
| url | https://doi.org/10.1002/hem3.70097 |
| work_keys_str_mv | AT henrichupe cellfreednafordetectionandmonitoringofextramedullaryamlrelapse AT clarapwienecke cellfreednafordetectionandmonitoringofextramedullaryamlrelapse AT stephanbartels cellfreednafordetectionandmonitoringofextramedullaryamlrelapse AT elisaschipper cellfreednafordetectionandmonitoringofextramedullaryamlrelapse AT jannikaleßmann cellfreednafordetectionandmonitoringofextramedullaryamlrelapse AT alinalasch cellfreednafordetectionandmonitoringofextramedullaryamlrelapse AT maximilianbader cellfreednafordetectionandmonitoringofextramedullaryamlrelapse AT razifgabdoulline cellfreednafordetectionandmonitoringofextramedullaryamlrelapse AT martinneugebohren cellfreednafordetectionandmonitoringofextramedullaryamlrelapse AT elkedammann cellfreednafordetectionandmonitoringofextramedullaryamlrelapse AT hanshkreipe cellfreednafordetectionandmonitoringofextramedullaryamlrelapse AT ulrichlehmann cellfreednafordetectionandmonitoringofextramedullaryamlrelapse AT ankekbergmann cellfreednafordetectionandmonitoringofextramedullaryamlrelapse AT nataliyadidonato cellfreednafordetectionandmonitoringofextramedullaryamlrelapse AT michaelstadler cellfreednafordetectionandmonitoringofextramedullaryamlrelapse AT matthiaseder cellfreednafordetectionandmonitoringofextramedullaryamlrelapse AT arnoldganser cellfreednafordetectionandmonitoringofextramedullaryamlrelapse AT florianhheidel cellfreednafordetectionandmonitoringofextramedullaryamlrelapse AT felicitasthol cellfreednafordetectionandmonitoringofextramedullaryamlrelapse AT michaelheuser cellfreednafordetectionandmonitoringofextramedullaryamlrelapse |