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 these methods across European LeukemiaNet (ELN) 2017 risk groups, using data from the HOVON-SAKK132 trial. In addition, we evaluated the optimal number of acquired white blood cells for accurate LSC detection and the prognostic value of individual LSC markers. Results show that it is essential to acquire at least 1x106 white blood cells in order to assess LSC-negativity accurately. Among various LSC markers, CD44 overexpression on CD34+CD38- cells was the only marker that was not statistically significant in our panel. Testing the impact of several published variations of LSC analysis on prognostic value for overall survival and cumulative incidence of relapse showed only 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 into the different methods of LSC definition can facilitate the clinical implementation. Trial registration EudraCT Number: 2013-002843-26.
Authors
- Angèle Kelder (ORCID: https://orcid.org/0000-0002-9643-4932)
- Jakob Robert Passweg (ORCID: https://orcid.org/0000-0001-7092-3351)
- Jannemieke Carbaat‐Ham
- Markus Gabriel Manz (ORCID: https://orcid.org/0000-0002-4676-7931)
- Mona M.H.E Fayed
- Arjan A. van de Loosdrecht (ORCID: https://orcid.org/0000-0001-8311-983X)
- Lok Lam Ngai (ORCID: https://orcid.org/0000-0003-0969-3766)
- Fleur Janssen
- Patrycja L. Gradowska (ORCID: https://orcid.org/0000-0002-4620-9163)
- Alexander N. Snel
- Diana Hanekamp (ORCID: https://orcid.org/0000-0002-5902-1127)
- Costa Bachas (ORCID: https://orcid.org/0000-0001-5983-6193)
- Jesse M. Tettero (ORCID: https://orcid.org/0000-0002-0811-0824)
- Thomas Pabst (ORCID: https://orcid.org/0000-0003-1493-806X)
- Bob Löwenberg (ORCID: https://orcid.org/0000-0001-8982-5217)
- Kimmo Porkka (ORCID: https://orcid.org/0000-0003-4112-5902)
- Bjørn Tore Gjertsen (ORCID: https://orcid.org/0000-0001-9358-9704)
- David C. de Leeuw (ORCID: https://orcid.org/0000-0003-4591-8467)
- Dimitri A. Breems
- Maaike A.M. Hofland
- Jacqueline J Cloos (ORCID: https://orcid.org/0000-0001-9150-8026)
- Laura Oudshoorn-van Marsbergen
- Peter J.M. Valk (ORCID: https://orcid.org/0000-0002-8857-9461)
- Laimonas Griškevičius (ORCID: https://orcid.org/0000-0002-3731-1537)
- Willemijn J. Scholten
- Gunnar Juliusson (ORCID: https://orcid.org/0000-0002-9457-5272)
- Johan A. Maertens (ORCID: https://orcid.org/0000-0003-4257-5980)
- Tom Reuvekamp (ORCID: https://orcid.org/0009-0001-1346-6606)
- Gert Jan Ossenkoppele
- Thomas Fischer (ORCID: https://orcid.org/0000-0001-5071-3808)
Institutions
- University of Helsinki (FI)
- Vilnius University (LT)
- Universitair Ziekenhuis Leuven (BE)
- Helsinki University Hospital (FI)
- Haukeland University Hospital (NO)
- Erasmus MC (NL)
- Amsterdam Neuroscience (NL)
- Skåne University Hospital (SE)
- Swiss Group For Clinical Cancer Research (CH)
- Erasmus MC Cancer Institute (NL)
- Ziekenhuisnetwerk Antwerpen Stuivenberg (BE)
- Amsterdam University Medical Centers (NL)
- Vrije Universiteit Amsterdam (NL)
- Otto-von-Guericke-Universität Magdeburg (DE)
Publication Details
- Journal
- Haematologica
- Published
- 2025-04-30
- DOI
- https://doi.org/10.3324/haematol.2024.287090
- Citations
- 1
- Primary Topic
- Acute Myeloid Leukemia Research
- Type
- article
- Field-Weighted Citation Impact
- 1.77
Funders
- Amgen
- Bristol-Myers Squibb
- Pfizer
- Gilead Sciences
- Alexion Pharmaceuticals
- Celgene
- Agios Pharmaceuticals
- Incyte
- Amsterdam University Medical Centers
- Astellas Pharma
- Universität Zürich
- Schweizerische Arbeitsgemeinschaft für Klinische Krebsforschung
- Genentech