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Sequential high-sensitivity mutational and chimerism analyses predict responses to post-transplant salvage therapies in MDS

Bone Marrow Transplantation volume 58, pages 100–102 (2023)Cite this article

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Fig. 1: The clinical courses and molecular characteristics of four representative patients.

Data availability

All ddPCR data generated or analysed during this study are included in this published article, in its Supplementary material file.

References

  1. Schmid C, de Wreede LC, van Biezen A, Finke J, Ehninger G, Ganser A, et al. Outcome after relapse of myelodysplastic syndrome and secondary acute myeloid leukemia following allogeneic stem cell transplantation: a retrospective registry analysis on 698 patients by the Chronic Malignancies Working Party of the European Society of Blood and Marrow Transplantation. Haematologica. 2018;103:237–45.

    Article  Google Scholar 

  2. Rautenberg C, Bergmann A, Germing U, Fischermanns C, Pechtel S, Kaivers J, et al. Prediction of response and survival following treatment with azacitidine for relapse of acute myeloid leukemia and myelodysplastic syndromes after allogeneic hematopoietic stem cell transplantation. Cancers. 2020;12:https://doi.org/10.3390/cancers12082255.

  3. Platzbecker U, Middeke JM, Sockel K, Herbst R, Wolf D, Baldus CD, et al. Measurable residual disease-guided treatment with azacitidine to prevent haematological relapse in patients with myelodysplastic syndrome and acute myeloid leukaemia (RELAZA2): an open-label, multicentre, phase 2 trial. Lancet Oncol. 2018;19:1668–79.

    Article  CAS  Google Scholar 

  4. Day E, Dear PH, McCaughan F. Digital PCR strategies in the development and analysis of molecular biomarkers for personalized medicine. Methods. 2013;59:101–7.

    Article  CAS  Google Scholar 

  5. Tozzo P, Delicati A, Zambello R, Caenazzo L. Chimerism monitoring techniques after hematopoietic stem cell transplantation: an overview of the last 15 years of innovations. Diagnostics. 2021;11:621.

    Article  Google Scholar 

  6. Jacque N, Nguyen S, Golmard JL, Uzunov M, Garnier A, Leblond V, et al. Chimerism analysis in peripheral blood using indel quantitative real-time PCR is a useful tool to predict post-transplant relapse in acute leukemia. Bone Marrow Transpl. 2015;50:259–65.

    Article  CAS  Google Scholar 

  7. George D, Czech J, John B, Yu M, Jennings LJ. Detection and quantification of chimerism by droplet digital PCR. Chimerism. 2013;4:102–8.

    Article  Google Scholar 

  8. Stahl T, Böhme MU, Kröger N, Fehse B. Digital PCR to assess hematopoietic chimerism after allogeneic stem cell transplantation. Exp Hematol. 2015;43:462–468.e1.

    Article  CAS  Google Scholar 

  9. Mika T, Baraniskin A, Ladigan S, Wulf G, Dierks S, Haase D, et al. Digital droplet PCR-based chimerism analysis for monitoring of hematopoietic engraftment after allogeneic stem cell transplantation. Int J Lab Hematol. 2019;41:615–21.

    Article  Google Scholar 

  10. Lee JM, Kim YJ, Park SS, Han E, Kim M, Kim Y. Simultaneous monitoring of mutation and chimerism using next-generation sequencing in myelodysplastic syndrome. J Clin Med. 2019;8:https://doi.org/10.3390/jcm8122077.

  11. Waterhouse M, Pfeifer D, Duque-Afonso J, Follo M, Duyster J, Depner M, et al. Droplet digital PCR for the simultaneous analysis of minimal residual disease and hematopoietic chimerism after allogeneic cell transplantation. Clin Chem Lab Med. 2019;57:641–7.

    Article  CAS  Google Scholar 

  12. Jacoby MA, Duncavage EJ, Chang GS, Miller CA, Shao J, Elliott K, et al. Subclones dominate at MDS progression following allogeneic hematopoietic cell transplant. JCI Insight. 2018;3:https://doi.org/10.1172/jci.insight.98962.

  13. Stahl T, Badbaran A, Kroger N, Klyuchnikov E, Zabelina T, Zeschke S, et al. Minimal residual disease diagnostics in patients with acute myeloid leukemia in the post-transplant period: comparison of peripheral blood and bone marrow analysis. Leuk Lymphoma. 2010;51:1837–43.

    Article  CAS  Google Scholar 

  14. Lucas F, Michaels PD, Wang D, Kim AS. Mutational analysis of hematologic neoplasms in 164 paired peripheral blood and bone marrow samples by next-generation sequencing. Blood Adv. 2020;4:4362–5.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

This study has been supported by grants from the Helsinki University Hospital Comprehensive Cancer Center and from the Southern Finland Regional Cancer Center (FICAN South). MiK received funding from the Finnish Cancer Institute, Finnish Medical Foundation and Cancer Society Finland. MM received funding from the Finnish Medical Foundation and the Finnish Cultural Foundation.

Author information

Authors and Affiliations

  1. Division of Hematology, Helsinki University Hospital, Comprehensive Cancer Center, Haartmaninkatu 4, 00290, Helsinki, Finland

    Freja Ebeling, Mika Kontro & Mikko Myllymäki

  2. Department of Internal Medicine, Porvoo Hospital, Helsinki and Uusimaa Hospital District, Porvoo, Finland

    Johanna Illman

  3. Laboratory of Genetics, HUS Diagnostic Center, Helsinki and Uusimaa Hospital District, Helsinki, Finland

    Matti Kankainen & Soili Kytölä

  4. Hematology Research Unit Helsinki, University of Helsinki and Helsinki University Hospital Comprehensive Cancer Center, Helsinki, Finland

    Matti Kankainen & Mikko Myllymäki

  5. Translational Immunology Research Program and Department of Clinical Chemistry and Hematology, University of Helsinki, Helsinki, Finland

    Matti Kankainen & Mikko Myllymäki

  6. iCAN Digital Precision Cancer Medicine Flagship, Helsinki, Finland

    Matti Kankainen

  7. Institute for Molecular Medicine Finland (FIMM), Helsinki Institute of Life Science, University of Helsinki, Helsinki, Finland

    Mika Kontro

  8. Foundation for the Finnish Cancer Institute, Helsinki, Finland

    Mika Kontro

  9. Department of Medicine, Kuopio University Hospital, Kuopio, Finland

    Anu Partanen

  10. Division of Hematology, Stem Cell Transplantation Unit, Helsinki University Hospital, Comprehensive Cancer Center, Helsinki, Finland

    Leila Sahlstedt & Riitta Niittyvuopio

Authors
  1. Freja Ebeling
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  2. Johanna Illman
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  8. Riitta Niittyvuopio
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  9. Soili Kytölä
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Contributions

FE was responsible for designing the study, compiled the clinical and molecular data and wrote the manuscript. JI recruited patients, followed their clinical courses and collected recipients of relapse interventions. MaK was responsible for designing Figs. 1, S1 and S2 and reviewing the molecular data. MiK was responsible for relapse treatments of patient 04. AP was responsible for follow-up patient samples from another hospital and reviewing the manuscript. LS was responsible for implementation of the study in the transplantation unit and recruiting patients and RN for the transplantation-related data of the patients. MM contributed to research discussion and data interpretation and wrote the manuscript. MM and JI performed the statistical analyses. SK was responsible for implementing the mutational and chimerism ddPCR analyses in HUSLAB as well as for NGS and collecting and reviewing the molecular data. All authors reviewed the manuscript during its preparation and approved the submission.

Corresponding author

Correspondence to Freja Ebeling.

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The authors declare no competing interests.

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Supplementary information

41409_2022_1847_MOESM1_ESM.pdf

Supplementary information: Patient cohort, Methods, Statistics and Figure design, Table S3, Table S4, Table S5, Figure S1, Figure S2, Figure S3, Figure S4, Table S6

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Ebeling, F., Illman, J., Kankainen, M. et al. Sequential high-sensitivity mutational and chimerism analyses predict responses to post-transplant salvage therapies in MDS. Bone Marrow Transplant 58, 100–102 (2023). https://doi.org/10.1038/s41409-022-01847-8

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