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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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Autores principales: Tettero, Jesse M., Al-Badri, Waleed K. W., Ngai, Lok Lam, Bachas, Costa, Breems, Dimitri A., van Elssen, Catharina H. M. J., Fischer, Thomas, Gjertsen, Bjorn T., van Gorkom, Gwendolyn N. Y., Gradowska, Patrycja, Greuter, Marjolein J. E., Griskevicius, Laimonas, Juliusson, Gunnar, Maertens, Johan, Manz, Markus G., Pabst, Thomas, Passweg, Jakob, Porkka, Kimmo, Löwenberg, Bob, Ossenkoppele, Gert J., Janssen, Jeroen J. W. M., Cloos, Jacqueline
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9589259/
https://www.ncbi.nlm.nih.gov/pubmed/36300090
http://dx.doi.org/10.3389/fonc.2022.999822
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author Tettero, Jesse M.
Al-Badri, Waleed K. W.
Ngai, Lok Lam
Bachas, Costa
Breems, Dimitri A.
van Elssen, Catharina H. M. J.
Fischer, Thomas
Gjertsen, Bjorn T.
van Gorkom, Gwendolyn N. Y.
Gradowska, Patrycja
Greuter, Marjolein J. E.
Griskevicius, Laimonas
Juliusson, Gunnar
Maertens, Johan
Manz, Markus G.
Pabst, Thomas
Passweg, Jakob
Porkka, Kimmo
Löwenberg, Bob
Ossenkoppele, Gert J.
Janssen, Jeroen J. W. M.
Cloos, Jacqueline
author_facet Tettero, Jesse M.
Al-Badri, Waleed K. W.
Ngai, Lok Lam
Bachas, Costa
Breems, Dimitri A.
van Elssen, Catharina H. M. J.
Fischer, Thomas
Gjertsen, Bjorn T.
van Gorkom, Gwendolyn N. Y.
Gradowska, Patrycja
Greuter, Marjolein J. E.
Griskevicius, Laimonas
Juliusson, Gunnar
Maertens, Johan
Manz, Markus G.
Pabst, Thomas
Passweg, Jakob
Porkka, Kimmo
Löwenberg, Bob
Ossenkoppele, Gert J.
Janssen, Jeroen J. W. M.
Cloos, Jacqueline
author_sort Tettero, Jesse M.
collection PubMed
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.
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spelling pubmed-95892592022-10-25 Concordance in measurable residual disease result after first and second induction cycle in acute myeloid leukemia: An outcome- and cost-analysis Tettero, Jesse M. Al-Badri, Waleed K. W. Ngai, Lok Lam Bachas, Costa Breems, Dimitri A. van Elssen, Catharina H. M. J. Fischer, Thomas Gjertsen, Bjorn T. van Gorkom, Gwendolyn N. Y. Gradowska, Patrycja Greuter, Marjolein J. E. Griskevicius, Laimonas Juliusson, Gunnar Maertens, Johan Manz, Markus G. Pabst, Thomas Passweg, Jakob Porkka, Kimmo Löwenberg, Bob Ossenkoppele, Gert J. Janssen, Jeroen J. W. M. Cloos, Jacqueline Front Oncol Oncology 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. Frontiers Media S.A. 2022-10-10 /pmc/articles/PMC9589259/ /pubmed/36300090 http://dx.doi.org/10.3389/fonc.2022.999822 Text en Copyright © 2022 Tettero, Al-Badri, Ngai, Bachas, Breems, van Elssen, Fischer, Gjertsen, van Gorkom, Gradowska, Greuter, Griskevicius, Juliusson, Maertens, Manz, Pabst, Passweg, Porkka, Löwenberg, Ossenkoppele, Janssen and Cloos https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Oncology
Tettero, Jesse M.
Al-Badri, Waleed K. W.
Ngai, Lok Lam
Bachas, Costa
Breems, Dimitri A.
van Elssen, Catharina H. M. J.
Fischer, Thomas
Gjertsen, Bjorn T.
van Gorkom, Gwendolyn N. Y.
Gradowska, Patrycja
Greuter, Marjolein J. E.
Griskevicius, Laimonas
Juliusson, Gunnar
Maertens, Johan
Manz, Markus G.
Pabst, Thomas
Passweg, Jakob
Porkka, Kimmo
Löwenberg, Bob
Ossenkoppele, Gert J.
Janssen, Jeroen J. W. M.
Cloos, Jacqueline
Concordance in measurable residual disease result after first and second induction cycle in acute myeloid leukemia: An outcome- and cost-analysis
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 Oncology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9589259/
https://www.ncbi.nlm.nih.gov/pubmed/36300090
http://dx.doi.org/10.3389/fonc.2022.999822
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