Leukaemic stem cell load at diagnosis predicts the development of relapse in young acute myeloid leukaemia patients

Hanekamp, Diana; Denys, Barbara; Kaspers, Gertjan J. L.; Marvelde, Jeroen G. te; Schuurhuis, Gerrit Jan; Haas, Valérie de; Moerloose, Barbara De; Bont, Eveline S. de; Zwaan, C. Michel; Jong, Anja W. M. de; Depreter, Barbara; Lammens, Tim; Philippé, Jan; Cloos, Jacqueline; Velden, Vincent H.J. van der

doi:10.1111/bjh.14991

Cited by 32 publications

(24 citation statements)

References 10 publications

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“…As knowledge on the makeup of the CD34+/CD38− fraction increased, other markers and properties were included anticipating better selectivity in defining LSC as previously summarized [5,29]. In studies on the prognostic impact of CD34+/CD38− LSC on disease outcome, the prognostic influence of complete absence of this fraction was also discovered: CD34− status, characterized by the complete absence of neoplastic CD34+ cells [18], turned out to be an independent prognostic factor identifying patients with better prognosis in adult [17] and pediatric AML [39] compared to patient with high or low CD34+/ CD38− LSC frequencies.…”

Section: Clinical Relevance Of Lsc Load For Prognosismentioning

confidence: 89%

Leukemic stem cells: identification and clinical application

2017

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Section: Clinical Relevance Of Lsc Load For Prognosismentioning

confidence: 89%

Leukemic stem cells: identification and clinical application

2017

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“…In AML, these have been shown to be the leukemic stem cells (LSC), which are characterized by CD34 + CD38 − expression in combination with an aberrant (LSC) marker not present on normal hematopoietic stem cells (HSC) ( 43 ). The LSC load at diagnosis and follow-up has a prognostic value either alone or together with the MFC-MRD results ( 44 – 49 ). Nevertheless, the development to incorporate LSC in the MFC-MRD assessment is still not on the level of the MFC-MRD regarding the technical recommendations.…”

Section: Advances In Current Measurable Residual Disease Techniquesmentioning

confidence: 99%

MRD Tailored Therapy in AML: What We Have Learned So Far

et al. 2021

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Acute myeloid leukemia (AML) is a heterogeneous clonal disease associated with a dismal survival, partly due to the frequent occurrence of relapse. Many patient- and leukemia-specific characteristics, such as age, cytogenetics, mutations, and measurable residual disease (MRD) after intensive chemotherapy, have shown to be valuable prognostic factors. MRD has become a rich field of research where many advances have been made regarding technical, biological, and clinical aspects, which will be the topic of this review. Since many laboratories involved in AML diagnostics have experience in immunophenotyping, multiparameter flow cytometry (MFC) based MRD is currently the most commonly used method. Although molecular, quantitative PCR based techniques may be more sensitive, their disadvantage is that they can only be applied in a subset of patients harboring the genetic aberration. Next-generation sequencing can assess and quantify mutations in many genes but currently does not offer highly sensitive MRD measurements on a routine basis. In order to provide reliable MRD results, MRD assay optimization and standardization is essential. Different techniques for MRD assessment are being evaluated, and combinations of the methods have shown promising results for improving its prognostic value. In this regard, the load of leukemic stem cells (LSC) has also been shown to add to the prognostic value of MFC-MRD. At this moment, MRD after intensive chemotherapy is most often used as a prognostic factor to help stratify patients, but also to select the most appropriate consolidation therapy. For example, to guide post-remission treatment for intermediate-risk patients where MRD positive patients receive allogeneic stem cell transplantation and MRD negative receive autologous stem cell transplantation. Other upcoming uses of MRD that are being investigated include: selecting the type of allogeneic stem cell transplantation therapy (donor, conditioning), monitoring after stem cell transplantation (to allow intervention), and determining drug efficacy for the use of a surrogate endpoint in clinical trials.

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“…While a single tube assay demonstrating different phenotypes of LSCs, as suggested recently (Hanekamp et al , ), can provide prognostic information, the extent to which it will be useful in the up‐front pursuit of possible treatment targets is perhaps more questionable. Still, it seems intuitive that flow cytometry can be used at diagnosis to evaluate LSC load and predict risk of treatment failure (Hanekamp et al , ). Indeed, a recent prospective study provides direct evidence that the frequency of immunophenotypically‐defined LSC at diagnosis and follow‐up independently predicts survival (Zeijlemaker et al , ).…”

Section: The Present Toolbox For Aml Lsc Characterisationmentioning

confidence: 99%

The concept of leukaemic stem cells in acute myeloid leukaemia 25 years on: hitting a moving target

et al. 2019

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Summary The concept of leukaemic stem cells (LSCs) was experimentally suggested 25 years ago through seminal data from John Dick's group, who showed that a small fraction of cells from acute myeloid leukaemia (AML) patients were able to be adoptively transferred into immunodeficient mice. The initial estimation of the frequency was 1:250 000 leukaemic cells, clearly indicating the difficulties ahead in translating knowledge on LSCs to the clinical setting. However, the field has steadily grown in interest, expanse and importance, concomitantly with the realisation of the molecular background for AML culminating in the sequencing of hundreds of AML genomes. The literature is now ripe with contributions describing how different molecular aberrations are more or less specific for LSCs, as well as reports showing selectivity in targeting LSCs in comparison to normal haematopoietic stem and progenitor cells. However, we argue here that these important data have not yet been fully realised within the clinical setting. In this clinically focused review, we outline the difficulties in identifying and defining LSCs at the individual patient level, with special emphasis on intraclonal heterogeneity. In addition, we suggest areas of future focus in order to realise the concept as real‐time benefit for AML patients.

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Leukaemic stem cell load at diagnosis predicts the development of relapse in young acute myeloid leukaemia patients

Cited by 32 publications

References 10 publications

Leukemic stem cells: identification and clinical application

Leukemic stem cells: identification and clinical application

MRD Tailored Therapy in AML: What We Have Learned So Far

The concept of leukaemic stem cells in acute myeloid leukaemia 25 years on: hitting a moving target

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