Different features of acute myeloid leukemia stem cell quantification in intensively treated patients

In acute myeloid leukemia, the burden of CD34+CD38- leukemia stem cells (LSC) has prognostic value at diagnosis and after induction chemotherapy. Since different methods of LSC quantification have been proposed, we determined the prognostic value on overall survival and incidence of relapse of thes...

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Main Authors: Lok Lam Ngai, Tom Reuvekamp, Diana Hanekamp, Fleur Janssen, Laura Oudshoorn-van Marsbergen, Jannemieke Carbaat-Ham, Maaike A.M. Hofland, Mona M.H.E. Fayed, Angèle Kelder, Willemijn J. Scholten, Alexander N. Snel, Costa Bachas, Jesse M. Tettero, Dimitri A. Breems, Thomas Fischer, Bjørn T. Gjertsen, Laimonas Griškevičius, Gunnar Juliusson, Arjan A. van de Loosdrecht, Johan A. Maertens, Markus G. Manz, Thomas Pabst, Jakob R. Passweg, Kimmo Porkka, Peter J.M. Valk, Patrycja Gradowska, Bob Löwenberg, Gert J. Ossenkoppele, David C. de Leeuw, Jacqueline Cloos
Format: Article
Language:English
Published: Ferrata Storti Foundation 2025-04-01
Series:Haematologica
Online Access:https://haematologica.org/article/view/12046
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author Lok Lam Ngai
Tom Reuvekamp
Diana Hanekamp
Fleur Janssen
Laura Oudshoorn-van Marsbergen
Jannemieke Carbaat-Ham
Maaike A.M. Hofland
Mona M.H.E. Fayed
Angèle Kelder
Willemijn J. Scholten
Alexander N. Snel
Costa Bachas
Jesse M. Tettero
Dimitri A. Breems
Thomas Fischer
Bjørn T. Gjertsen
Laimonas Griškevičius
Gunnar Juliusson
Arjan A. van de Loosdrecht
Johan A. Maertens
Markus G. Manz
Thomas Pabst
Jakob R. Passweg
Kimmo Porkka
Peter J.M. Valk
Patrycja Gradowska
Bob Löwenberg
Gert J. Ossenkoppele
David C. de Leeuw
Jacqueline Cloos
author_facet Lok Lam Ngai
Tom Reuvekamp
Diana Hanekamp
Fleur Janssen
Laura Oudshoorn-van Marsbergen
Jannemieke Carbaat-Ham
Maaike A.M. Hofland
Mona M.H.E. Fayed
Angèle Kelder
Willemijn J. Scholten
Alexander N. Snel
Costa Bachas
Jesse M. Tettero
Dimitri A. Breems
Thomas Fischer
Bjørn T. Gjertsen
Laimonas Griškevičius
Gunnar Juliusson
Arjan A. van de Loosdrecht
Johan A. Maertens
Markus G. Manz
Thomas Pabst
Jakob R. Passweg
Kimmo Porkka
Peter J.M. Valk
Patrycja Gradowska
Bob Löwenberg
Gert J. Ossenkoppele
David C. de Leeuw
Jacqueline Cloos
author_sort Lok Lam Ngai
collection DOAJ
description In acute myeloid leukemia, the burden of CD34+CD38- leukemia stem cells (LSC) has prognostic value at diagnosis and after induction chemotherapy. Since different methods of LSC quantification have been proposed, we determined the prognostic value on overall survival and incidence of relapse of these methods across ELN2017 risk groups, using data from the HOVON-SAKK132 trial. In addition, we have evaluated the optimal number of acquired white blood cells for accurate LSC detection and the prognostic value of individual LSC markers. Results show that acquiring 1 million white blood cells is essential for accurate LSC-negativity assessment. Among different LSC markers, CD44 overexpression on CD34+CD38- cells was the only insignificant marker in our panel. Testing the impact of several published variations on the analysis for LSC assessments on prognostic value for overall survival and cumulative incidence of relapse, showed marginal differences, demonstrating the robust prognostic value of LSC burden. For further clinical implementation, the optimal LSC assessment may differ among ELN risk groups. In conclusion, LSC burden is a robust prognostic factor and insight in the different methods of LSC definition can facilitate the clinical implementation.
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spelling doaj-art-7efccb4512a14e12b4a46fa6c6d8edde2025-08-20T02:19:50ZengFerrata Storti FoundationHaematologica0390-60781592-87212025-04-01999110.3324/haematol.2024.287090Different features of acute myeloid leukemia stem cell quantification in intensively treated patientsLok Lam Ngai0Tom Reuvekamp1Diana Hanekamp2Fleur Janssen3Laura Oudshoorn-van Marsbergen4Jannemieke Carbaat-Ham5Maaike A.M. Hofland6Mona M.H.E. Fayed7Angèle Kelder8Willemijn J. Scholten9Alexander N. Snel10Costa Bachas11Jesse M. Tettero12Dimitri A. Breems13Thomas Fischer14Bjørn T. Gjertsen15Laimonas Griškevičius16Gunnar Juliusson17Arjan A. van de Loosdrecht18Johan A. Maertens19Markus G. Manz20Thomas Pabst21Jakob R. Passweg22Kimmo Porkka23Peter J.M. Valk24Patrycja Gradowska25Bob Löwenberg26Gert J. Ossenkoppele27David C. de Leeuw28Jacqueline Cloos29Amsterdam UMC location Vrije Universiteit Amsterdam, Department of Hematology, Amsterdam, The Netherlands; Cancer Center Amsterdam, Imaging and Biomarkers, AmsterdamAmsterdam UMC location Vrije Universiteit Amsterdam, Department of Hematology, Amsterdam, The Netherlands; Cancer Center Amsterdam, Imaging and Biomarkers, Amsterdam, The Netherlands; Amsterdam UMC location Universiteit van Amsterdam, Department of Hematology, AmsterdamAmsterdam UMC location Vrije Universiteit Amsterdam, Department of Hematology, Amsterdam, The Netherlands; Cancer Center Amsterdam, Imaging and Biomarkers, Amsterdam, The Netherlands; Erasmus University Medical Center, Department of Hematology, RotterdamAmsterdam UMC location Vrije Universiteit Amsterdam, Department of Hematology, Amsterdam, The Netherlands; Cancer Center Amsterdam, Imaging and Biomarkers, AmsterdamAmsterdam UMC location Vrije Universiteit Amsterdam, Department of Hematology, Amsterdam, The Netherlands; Cancer Center Amsterdam, Imaging and Biomarkers, AmsterdamAmsterdam UMC location Vrije Universiteit Amsterdam, Department of Hematology, Amsterdam, The Netherlands; Cancer Center Amsterdam, Imaging and Biomarkers, AmsterdamAmsterdam UMC location Vrije Universiteit Amsterdam, Department of Hematology, Amsterdam, The Netherlands; Cancer Center Amsterdam, Imaging and Biomarkers, AmsterdamAmsterdam UMC location Vrije Universiteit Amsterdam, Department of Hematology, Amsterdam, The Netherlands; Cancer Center Amsterdam, Imaging and Biomarkers, AmsterdamAmsterdam UMC location Vrije Universiteit Amsterdam, Department of Hematology, Amsterdam, The Netherlands; Cancer Center Amsterdam, Imaging and Biomarkers, AmsterdamAmsterdam UMC location Vrije Universiteit Amsterdam, Department of Hematology, Amsterdam, The Netherlands; Cancer Center Amsterdam, Imaging and Biomarkers, AmsterdamAmsterdam UMC location Vrije Universiteit Amsterdam, Department of Hematology, Amsterdam, The Netherlands; Cancer Center Amsterdam, Imaging and Biomarkers, AmsterdamAmsterdam UMC location Vrije Universiteit Amsterdam, Department of Hematology, Amsterdam, The Netherlands; Cancer Center Amsterdam, Imaging and Biomarkers, AmsterdamAmsterdam UMC location Vrije Universiteit Amsterdam, Department of Hematology, Amsterdam, The Netherlands; Cancer Center Amsterdam, Imaging and Biomarkers, AmsterdamZiekenhuis aan de Stroom, Department of Hematology, AntwerpOtto von Guericke University Hospital Magdeburg, MagdeburgHaukeland University Hospital, BergenVilnius University Hospital Santaros Klinikos and Vilnius University, Vilnius, LithuaniaSkanes University Hospital, LundAmsterdam UMC location Vrije Universiteit Amsterdam, Department of Hematology, Amsterdam, The Netherlands; Cancer Center Amsterdam, Imaging and Biomarkers, AmsterdamUniversity Hospital Gasthuisberg, LeuvenUniversity Hospital, Zurich, Switzerland; Swiss Group for Clinical Cancer Research (SAKK)Swiss Group for Clinical Cancer Research (SAKK); Department of Medical Oncology, Inselspital; University Hospital, BernSwiss Group for Clinical Cancer Research (SAKK); Department of Medical Oncology, Inselspital; University Hospital, Bern, Switzerland; University Hospital, BaselHelsinki University Hospital Cancer Center, HelsinkiErasmus University Medical Center, Department of Hematology, RotterdamHOVON Foundation, Rotterdam, the Netherlands; Department of Hematology, Erasmus MC Cancer Institute, RotterdamErasmus University Medical Center, Department of Hematology, Rotterdam, Netherlands; Department of Hematology, Erasmus MC Cancer Institute, RotterdamAmsterdam UMC location Vrije Universiteit Amsterdam, Department of Hematology, Amsterdam, The Netherlands; Cancer Center Amsterdam, Imaging and Biomarkers, AmsterdamAmsterdam UMC location Vrije Universiteit Amsterdam, Department of Hematology, Amsterdam, The Netherlands; Cancer Center Amsterdam, Imaging and Biomarkers, AmsterdamAmsterdam UMC location Vrije Universiteit Amsterdam, Department of Hematology, Amsterdam, The Netherlands; Cancer Center Amsterdam, Imaging and Biomarkers, Amsterdam In acute myeloid leukemia, the burden of CD34+CD38- leukemia stem cells (LSC) has prognostic value at diagnosis and after induction chemotherapy. Since different methods of LSC quantification have been proposed, we determined the prognostic value on overall survival and incidence of relapse of these methods across ELN2017 risk groups, using data from the HOVON-SAKK132 trial. In addition, we have evaluated the optimal number of acquired white blood cells for accurate LSC detection and the prognostic value of individual LSC markers. Results show that acquiring 1 million white blood cells is essential for accurate LSC-negativity assessment. Among different LSC markers, CD44 overexpression on CD34+CD38- cells was the only insignificant marker in our panel. Testing the impact of several published variations on the analysis for LSC assessments on prognostic value for overall survival and cumulative incidence of relapse, showed marginal differences, demonstrating the robust prognostic value of LSC burden. For further clinical implementation, the optimal LSC assessment may differ among ELN risk groups. In conclusion, LSC burden is a robust prognostic factor and insight in the different methods of LSC definition can facilitate the clinical implementation. https://haematologica.org/article/view/12046
spellingShingle Lok Lam Ngai
Tom Reuvekamp
Diana Hanekamp
Fleur Janssen
Laura Oudshoorn-van Marsbergen
Jannemieke Carbaat-Ham
Maaike A.M. Hofland
Mona M.H.E. Fayed
Angèle Kelder
Willemijn J. Scholten
Alexander N. Snel
Costa Bachas
Jesse M. Tettero
Dimitri A. Breems
Thomas Fischer
Bjørn T. Gjertsen
Laimonas Griškevičius
Gunnar Juliusson
Arjan A. van de Loosdrecht
Johan A. Maertens
Markus G. Manz
Thomas Pabst
Jakob R. Passweg
Kimmo Porkka
Peter J.M. Valk
Patrycja Gradowska
Bob Löwenberg
Gert J. Ossenkoppele
David C. de Leeuw
Jacqueline Cloos
Different features of acute myeloid leukemia stem cell quantification in intensively treated patients
Haematologica
title Different features of acute myeloid leukemia stem cell quantification in intensively treated patients
title_full Different features of acute myeloid leukemia stem cell quantification in intensively treated patients
title_fullStr Different features of acute myeloid leukemia stem cell quantification in intensively treated patients
title_full_unstemmed Different features of acute myeloid leukemia stem cell quantification in intensively treated patients
title_short Different features of acute myeloid leukemia stem cell quantification in intensively treated patients
title_sort different features of acute myeloid leukemia stem cell quantification in intensively treated patients
url https://haematologica.org/article/view/12046
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