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ACUTE MYELOID LEUKEMIA

Peri-transplant flow-MRD assessment of cells with leukemic stem cells (LSC) associated phenotype in AML patients undergoing allogeneic stem cell transplantation in CR

Leukemia volume 38, pages 386–388 (2024)Cite this article

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Minimal residual disease (MRD) is a well-established prognostic marker that allows subdivision of AML patients into different risk groups independently of the methods being used and cut-offs [1,2,3]. Moreover, the MRD status may be used to guide the use of intensive (e.g. allo-SCT) or non-intensive (e.g. chemotherapy and/or autologous stem cell transplantation) treatment for AML patients with intermediate risk [4]. Thus, conventional (c) MRD detection is gaining more relevance in the non-transplant and transplant setting as well [5]. Clonal evolution, antigen shifting during treatment, and poor quality of bone marrow samples may lead to false-negative results [6]. On the other hand, some specific cell populations may mimic leukemic blasts and lead to false-positive results [7]. Leukemic stem cells (LSC) have unique biological properties, and possess a lower sensitivity to anti-leukemic treatment compared with AML blasts [8]. Though the studies on impact of LSC in transplant settings are limited, several researchers have suggested that LSC detection by multi-colored flow cytometry (MFC) has a predictive value for post-transplant relapses [9,10,11,12].

In the present study, we compared cMRD and LSC-based MFC-MRD approaches in the peri-transplant period in 90 adult AML patients (Supplementary Table 1S) who received allogeneic stem cell transplantation at the University Medical Center Hamburg-Eppendorf from 01/2020 to 06/2023. We investigated if LSC-based MRD-MFC approach may improve relapse prediction. Allografts were performed in the majority from matched unrelated donors (n = 63) after myeloablative conditioning (n = 62). A total of 28 patients had reduced intensity conditioning. Immunophenotypic analysis was done on whole bone marrow specimens after stain-lyse-wash standard techniques with a sensitivity of 10−4–10−5 [2]. Immunophenotypic analysis for LSC detection was performed on whole bone marrow specimens according to Zeijlemaker et al. with a cut-off of 0.005% of white blood cells (WBC) [13].

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Fig. 1: Outcomes for 90 AML patients after allo-SCT according to pre-transplant LSC status.

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Acknowledgements

The authors are grateful to all colleagues from the department of stem cell transplantation including laboratory for providing the necessary data.

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Authors and Affiliations

  1. Department for Stem Cell Transplantation, University Cancer Centre Hamburg-Eppendorf, Hamburg, Germany

    Evgeny Klyuchnikov, Anita Badbaran, Radwan Massoud, Petra Freiberger, Christine Wolschke, Francis Ayuk, Boris Fehse & Nicolaus Kröger

  2. Department of Hematology and Central Hematology Laboratory, Inselspital, Bern University Hospital, Bern, Switzerland

    Ulrike Bacher

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  1. Evgeny Klyuchnikov
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Contributions

EK and NK designed study, performed the analysis and wrote the manuscript; PF performed the laboratory measurements; AB and BF performed the laboratory measurements and participated in data interpretation; UB provided critical suggestions for improving the manuscript; RM, FA and CW provided patents’ data and supported by manuscripts’ preparation. All authors read the final manuscript and participated in the discussion of results.

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Correspondence to Evgeny Klyuchnikov.

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Klyuchnikov, E., Badbaran, A., Massoud, R. et al. Peri-transplant flow-MRD assessment of cells with leukemic stem cells (LSC) associated phenotype in AML patients undergoing allogeneic stem cell transplantation in CR. Leukemia 38, 386–388 (2024). https://doi.org/10.1038/s41375-024-02148-3

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