Concordance in measurable residual disease result after first and second induction cycle in acute myeloid leukemia: An outcome- and cost-analysis
Measurable residual disease (MRD) measured using multiparameter flow-cytometry (MFC) has proven to be an important prognostic biomarker in acute myeloid leukemia (AML). In addition, MRD is increasingly used to guide consolidation treatment towards a non-allogenic stem cell transplantation treatment...
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Frontiers Media S.A.
2022-10-01
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| Series: | Frontiers in Oncology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2022.999822/full |
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| author | Jesse M. Tettero Jesse M. Tettero Waleed K. W. Al-Badri Lok Lam Ngai Lok Lam Ngai Costa Bachas Costa Bachas Dimitri A. Breems Catharina H. M. J. van Elssen Thomas Fischer Bjorn T. Gjertsen Gwendolyn N. Y. van Gorkom Patrycja Gradowska Marjolein J. E. Greuter Laimonas Griskevicius Gunnar Juliusson Johan Maertens Markus G. Manz Markus G. Manz Thomas Pabst Thomas Pabst Jakob Passweg Jakob Passweg Kimmo Porkka Bob Löwenberg Gert J. Ossenkoppele Gert J. Ossenkoppele Jeroen J. W. M. Janssen Jeroen J. W. M. Janssen Jacqueline Cloos Jacqueline Cloos |
| author_facet | Jesse M. Tettero Jesse M. Tettero Waleed K. W. Al-Badri Lok Lam Ngai Lok Lam Ngai Costa Bachas Costa Bachas Dimitri A. Breems Catharina H. M. J. van Elssen Thomas Fischer Bjorn T. Gjertsen Gwendolyn N. Y. van Gorkom Patrycja Gradowska Marjolein J. E. Greuter Laimonas Griskevicius Gunnar Juliusson Johan Maertens Markus G. Manz Markus G. Manz Thomas Pabst Thomas Pabst Jakob Passweg Jakob Passweg Kimmo Porkka Bob Löwenberg Gert J. Ossenkoppele Gert J. Ossenkoppele Jeroen J. W. M. Janssen Jeroen J. W. M. Janssen Jacqueline Cloos Jacqueline Cloos |
| author_sort | Jesse M. Tettero |
| collection | DOAJ |
| description | Measurable residual disease (MRD) measured using multiparameter flow-cytometry (MFC) has proven to be an important prognostic biomarker in acute myeloid leukemia (AML). In addition, MRD is increasingly used to guide consolidation treatment towards a non-allogenic stem cell transplantation treatment for MRD-negative patients in the ELN-2017 intermediate risk group. Currently, measurement of MFC-MRD in bone marrow is used for clinical decision making after 2 cycles of induction chemotherapy. However, measurement after 1 cycle has also been shown to have prognostic value, so the optimal time point remains a question of debate. We assessed the independent prognostic value of MRD results at either time point and concordance between these for 273 AML patients treated within and according to the HOVON-SAKK 92, 102, 103 and 132 trials. Cumulative incidence of relapse, event free survival and overall survival were significantly better for MRD-negative (<0.1%) patients compared to MRD-positive patients after cycle 1 and cycle 2 (p ≤ 0.002, for all comparisons). A total of 196 patients (71.8%) were MRD-negative after cycle 1, of which the vast majority remained negative after cycle 2 (180 patients; 91.8%). In contrast, of the 77 MRD-positive patients after cycle 1, only 41 patients (53.2%) remained positive. A cost reduction of –€571,751 per 100 patients could be achieved by initiating the donor search based on the MRD-result after cycle 1. This equals to a 50.7% cost reduction compared to the current care strategy in which the donor search is initiated for all patients. These results show that MRD after cycle 1 has prognostic value and is highly concordant with MRD status after cycle 2. When MRD-MFC is used to guide consolidation treatment (allo vs non-allo) in intermediate risk patients, allogeneic donor search may be postponed or omitted after cycle 1. Since the majority of MRD-negative patients remain negative after cycle 2, this could safely reduce the number of allogeneic donor searches and reduce costs. |
| first_indexed | 2024-04-11T17:04:45Z |
| format | Article |
| id | doaj.art-56f5490a20524932aafd0bb2d3219e7c |
| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-04-11T17:04:45Z |
| publishDate | 2022-10-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj.art-56f5490a20524932aafd0bb2d3219e7c2022-12-22T04:13:03ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2022-10-011210.3389/fonc.2022.999822999822Concordance in measurable residual disease result after first and second induction cycle in acute myeloid leukemia: An outcome- and cost-analysisJesse M. Tettero0Jesse M. Tettero1Waleed K. W. Al-Badri2Lok Lam Ngai3Lok Lam Ngai4Costa Bachas5Costa Bachas6Dimitri A. Breems7Catharina H. M. J. van Elssen8Thomas Fischer9Bjorn T. Gjertsen10Gwendolyn N. Y. van Gorkom11Patrycja Gradowska12Marjolein J. E. Greuter13Laimonas Griskevicius14Gunnar Juliusson15Johan Maertens16Markus G. Manz17Markus G. Manz18Thomas Pabst19Thomas Pabst20Jakob Passweg21Jakob Passweg22Kimmo Porkka23Bob Löwenberg24Gert J. Ossenkoppele25Gert J. Ossenkoppele26Jeroen J. W. M. Janssen27Jeroen J. W. M. Janssen28Jacqueline Cloos29Jacqueline Cloos30Department of Hematology, Amsterdam Univerisity Medical Centers location Vrije Universiteit Amsterdam, Amsterdam, NetherlandsCancer Center Amsterdam, Imaging and Biomarkers, Amsterdam, NetherlandsDepartment of Hematology, Amsterdam Univerisity Medical Centers location Vrije Universiteit Amsterdam, Amsterdam, NetherlandsDepartment of Hematology, Amsterdam Univerisity Medical Centers location Vrije Universiteit Amsterdam, Amsterdam, NetherlandsCancer Center Amsterdam, Imaging and Biomarkers, Amsterdam, NetherlandsDepartment of Hematology, Amsterdam Univerisity Medical Centers location Vrije Universiteit Amsterdam, Amsterdam, NetherlandsCancer Center Amsterdam, Imaging and Biomarkers, Amsterdam, NetherlandsDepartment of Hematology, Ziekenhuis Netwerk Antwerpen, Antwerp, BelgiumDepartment of Internal Medicine, Division of Hematology, GROW-School for Oncology and Developmental Biology, Maastricht University Medical Center, Maastricht, NetherlandsDepartment of Hematology and Oncology, Otto von Guericke University Hospital Magdeburg, Magdeburg, GermanyDepartment of Medicine, Hematology Section, Haukeland University Hospital, Bergen, NorwayDepartment of Internal Medicine, Division of Hematology, GROW-School for Oncology and Developmental Biology, Maastricht University Medical Center, Maastricht, NetherlandsThe Dutch-Belgian Hemato-Oncology Cooperative Group (HOVON) Data Center, Department of Hematology, Erasmus Medical Center (MC) Cancer Institute, Rotterdam, NetherlandsDepartment of Epidemiology and Data Science, Amsterdam Univerisity Medical Centers, location Vrije Universiteit Amsterdam, Amsterdam, NetherlandsHematology, Oncology, Transfusion Medicine Center, Vilnius University Hospital Santaros Klinikos and Vilnius University, Vilnius, Lithuania0Department of Hematology, Skanes University Hospital, Lund, Sweden1Department of Hematology, University Hospital Gasthuisberg, Leuven, Belgium2Department of Medical Oncology and Hematology, University Hospital, Zurich, Switzerland3Swiss Group for Clinical Cancer Research (SAKK), Bern, Switzerland3Swiss Group for Clinical Cancer Research (SAKK), Bern, Switzerland4Department of Medical Oncology, Inselspital, University Hospital, Bern, Switzerland3Swiss Group for Clinical Cancer Research (SAKK), Bern, Switzerland5Department of Hematology, University Hospital, Basel, Switzerland6Department of Hematology, Helsinki University Hospital Cancer Center, Helsinki, Finland7Department of Hematology, Erasmus University Medical Center (MC) and Erasmus MC Cancer Institute, Rotterdam, NetherlandsDepartment of Hematology, Amsterdam Univerisity Medical Centers location Vrije Universiteit Amsterdam, Amsterdam, NetherlandsCancer Center Amsterdam, Imaging and Biomarkers, Amsterdam, NetherlandsDepartment of Hematology, Amsterdam Univerisity Medical Centers location Vrije Universiteit Amsterdam, Amsterdam, NetherlandsCancer Center Amsterdam, Imaging and Biomarkers, Amsterdam, NetherlandsDepartment of Hematology, Amsterdam Univerisity Medical Centers location Vrije Universiteit Amsterdam, Amsterdam, NetherlandsCancer Center Amsterdam, Imaging and Biomarkers, Amsterdam, NetherlandsMeasurable residual disease (MRD) measured using multiparameter flow-cytometry (MFC) has proven to be an important prognostic biomarker in acute myeloid leukemia (AML). In addition, MRD is increasingly used to guide consolidation treatment towards a non-allogenic stem cell transplantation treatment for MRD-negative patients in the ELN-2017 intermediate risk group. Currently, measurement of MFC-MRD in bone marrow is used for clinical decision making after 2 cycles of induction chemotherapy. However, measurement after 1 cycle has also been shown to have prognostic value, so the optimal time point remains a question of debate. We assessed the independent prognostic value of MRD results at either time point and concordance between these for 273 AML patients treated within and according to the HOVON-SAKK 92, 102, 103 and 132 trials. Cumulative incidence of relapse, event free survival and overall survival were significantly better for MRD-negative (<0.1%) patients compared to MRD-positive patients after cycle 1 and cycle 2 (p ≤ 0.002, for all comparisons). A total of 196 patients (71.8%) were MRD-negative after cycle 1, of which the vast majority remained negative after cycle 2 (180 patients; 91.8%). In contrast, of the 77 MRD-positive patients after cycle 1, only 41 patients (53.2%) remained positive. A cost reduction of –€571,751 per 100 patients could be achieved by initiating the donor search based on the MRD-result after cycle 1. This equals to a 50.7% cost reduction compared to the current care strategy in which the donor search is initiated for all patients. These results show that MRD after cycle 1 has prognostic value and is highly concordant with MRD status after cycle 2. When MRD-MFC is used to guide consolidation treatment (allo vs non-allo) in intermediate risk patients, allogeneic donor search may be postponed or omitted after cycle 1. Since the majority of MRD-negative patients remain negative after cycle 2, this could safely reduce the number of allogeneic donor searches and reduce costs.https://www.frontiersin.org/articles/10.3389/fonc.2022.999822/fullacute myeloid leukemiameasurable residual disease (MRD)multiparameter flow cytometry (MFC)prognostic valueearlier detectionguided therapy |
| spellingShingle | Jesse M. Tettero Jesse M. Tettero Waleed K. W. Al-Badri Lok Lam Ngai Lok Lam Ngai Costa Bachas Costa Bachas Dimitri A. Breems Catharina H. M. J. van Elssen Thomas Fischer Bjorn T. Gjertsen Gwendolyn N. Y. van Gorkom Patrycja Gradowska Marjolein J. E. Greuter Laimonas Griskevicius Gunnar Juliusson Johan Maertens Markus G. Manz Markus G. Manz Thomas Pabst Thomas Pabst Jakob Passweg Jakob Passweg Kimmo Porkka Bob Löwenberg Gert J. Ossenkoppele Gert J. Ossenkoppele Jeroen J. W. M. Janssen Jeroen J. W. M. Janssen Jacqueline Cloos Jacqueline Cloos Concordance in measurable residual disease result after first and second induction cycle in acute myeloid leukemia: An outcome- and cost-analysis Frontiers in Oncology acute myeloid leukemia measurable residual disease (MRD) multiparameter flow cytometry (MFC) prognostic value earlier detection guided therapy |
| title | Concordance in measurable residual disease result after first and second induction cycle in acute myeloid leukemia: An outcome- and cost-analysis |
| title_full | Concordance in measurable residual disease result after first and second induction cycle in acute myeloid leukemia: An outcome- and cost-analysis |
| title_fullStr | Concordance in measurable residual disease result after first and second induction cycle in acute myeloid leukemia: An outcome- and cost-analysis |
| title_full_unstemmed | Concordance in measurable residual disease result after first and second induction cycle in acute myeloid leukemia: An outcome- and cost-analysis |
| title_short | Concordance in measurable residual disease result after first and second induction cycle in acute myeloid leukemia: An outcome- and cost-analysis |
| title_sort | concordance in measurable residual disease result after first and second induction cycle in acute myeloid leukemia an outcome and cost analysis |
| topic | acute myeloid leukemia measurable residual disease (MRD) multiparameter flow cytometry (MFC) prognostic value earlier detection guided therapy |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2022.999822/full |
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