Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Article
  • Published:

Prognostic impact of chromosomal changes at relapse after allogeneic hematopoietic cell transplantation for acute myeloid leukemia or myelodysplastic syndrome

Bone Marrow Transplantation volume 57, pages 810–816 (2022)Cite this article

Subjects

Abstract

Chromosome analysis is a powerful prognostic tool in myeloid malignancies. Recipients who experience relapse after allogeneic hematopoietic cell transplantation (allo-HCT) often show chromosomal changes between diagnosis and relapse. However, the clinical impact of chromosomal changes and the efficacy of post-relapse treatment according to chromosomal changes have not been fully investigated. We retrospectively analyzed 72 recipients who had experienced relapse after allo-HCT for acute myeloid leukemia or myelodysplastic syndrome. We categorized them into two groups: with or without clonal chromosomal changes at relapse after allo-HCT. Post-relapse survival was shorter in the clonal chromosomal change group (median 117 days vs 275 days, P = 0.019). Moreover, acquisition of chromosome 7 abnormality or complex changes tended to be associated with inferior survival in a univariate analysis (median 92 days vs median 173 days, P = 0.043), and this adverse impact was confirmed in a multivariate analysis (hazard ratio 2.07, P = 0.024). The patterns of chromosomal changes from diagnosis to relapse after allo-HCT were heterogenous, and further investigations are required to clarify the effect of individual chromosomal changes.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Fig. 1: Treatment after post-transplant relapse.
Fig. 2: Chromosomal changes added from diagnosis to relapse.
Fig. 3: The timing and details of chromosomal changes.
Fig. 4: Post-relapse survival.
Fig. 5: Post-relapse survival according to chromosome 7 or complex changes.

Similar content being viewed by others

Data availability

All data generated or analysed during this study are included in this published article (and its supplementary information files).

References

  1. Grimwade D, Ivey A, Huntly BJ. Molecular landscape of acute myeloid leukemia in younger adults and its clinical relevance. Blood 2016;127:29–41.

    Article  CAS  Google Scholar 

  2. Bochtler T, Fröhling S, Krämer A. Role of chromosomal aberrations in clonal diversity and progression of acute myeloid leukemia. Leukemia 2015;29:1243–52.

    Article  CAS  Google Scholar 

  3. de Lima M, Porter DL, Battiwalla M, Bishop MR, Giralt SA, Hardy NM, et al. Proceedings from the National cancer institute’s second international workshop on the biology, prevention, and treatment of relapse after hematopoietic stem cell transplantation: Part III. Prevention and treatment of relapse after allogeneic transplantation. Biol Blood Marrow Transpl. 2014;20:4–13.

    Article  Google Scholar 

  4. Yuasa M, Yamamoto H, Mitsuki T, Kageyama K, Kaji D, Taya Y, et al. Prognostic impact of cytogenetic evolution on the outcome of allogeneic stem cell transplantation in patients with acute myeloid leukemia in nonremission: A single-institute analysis of 212 recipients. Biol Blood Marrow Transpl. 2020;26:2262–70.

    Article  CAS  Google Scholar 

  5. Ertz-Archambault N, Kosiorek H, Slack JL, Lonzo ML, Greipp PT, Khera N, et al. Cytogenetic evolution in myeloid neoplasms at relapse after allogeneic hematopoietic cell transplantation: Association with previous chemotherapy and effect on survival. Biol Blood Marrow Transpl. 2017;23:782–9.

    Article  CAS  Google Scholar 

  6. Karrman K, Sallerfors B, Lenhoff S, Fioretos T, Johansson B. Cytogenetic evolution patterns in CML post-SCT. Bone Marrow Transpl. 2007;39:165–71.

    Article  CAS  Google Scholar 

  7. Kern W, Haferlach T, Schnittger S, Ludwig WD, Hiddemann W, Schoch C. Karyotype instability between diagnosis and relapse in 117 patients with acute myeloid leukemia: implications for resistance against therapy. Leukemia 2002;16:2084–91.

    Article  CAS  Google Scholar 

  8. Bacher U, Haferlach T, Alpermann T, Zenger M, Kröger N, Beelen DW, et al. Comparison of cytogenetic clonal evolution patterns following allogeneic hematopoietic transplantation versus conventional treatment in patients at relapse of AML. Biol Blood Marrow Transpl. 2010;16:1649–57.

    Article  Google Scholar 

  9. Armand P, Kim HT, Logan BR, Wang Z, Alyea EP, Kalaycio ME, et al. Validation and refinement of the Disease Risk Index for allogeneic stem cell transplantation. Blood 2014;123:3664–71.

    Article  CAS  Google Scholar 

  10. Mitelman F. ISCN 1995: An international system for human cytogenetic nomenclature (1995): Recommendations of the International Standing Committee on Human Cytogenetic Nomenclature: Memphis, TN, USA, October 9-13, 1994.

  11. Shaffer LG, Tommerup N. ISCN 2005: an international system for human cytogenetic nomenclature (2005): Recommendations of the International Standing Committee on Human Cytogenetic Nomenclature.

  12. International Standing Committee on HumanCytogenetic N, Shaffer LG, Slovak ML, Campbell LJ. ISCN 2009: An international system for human cytogenetic nomenclature (2009): Recommendations of the International Standing Committee on Human Cytogenetic Nomenclature.

  13. Shaffer LG, McGowan-Jordan J, Schmid M. ISCN 2013: An international system for human cytogenetic nomenclature (2013): Recommendations of the International Standing Committee on Human Cytogenetic Nomenclature.

  14. McGowan-Jordan J, Simons A, Schmid M. ISCN 2016: An international system for human cytogenomic nomenclature (2016).

  15. McGowan-Jordan J, Hastings RJ, Moore S. ISCN 2020: An international system for human cytogenomic nomenclature (2020).

  16. Fungtammasan A, Walsh E, Chiaromonte F, Eckert KA, Makova KD. A genome-wide analysis of common fragile sites: what features determine chromosomal instability in the human genome? Genome Res. 2012;22:993–1005.

    Article  CAS  Google Scholar 

  17. Döhner H, Estey E, Grimwade D, Amadori S, Appelbaum FR, Büchner T, et al. Diagnosis and management of AML in adults: 2017 ELN recommendations from an international expert panel. Blood 2017;129:424–47.

    Article  Google Scholar 

  18. Greenberg PL, Tuechler H, Schanz J, Sanz G, Garcia-Manero G, Solé F, et al. Revised international prognostic scoring system for myelodysplastic syndromes. Blood 2012;120:2454–65.

    Article  CAS  Google Scholar 

  19. Kanda Y. Investigation of the freely available easy-to-use software ‘EZR’ for medical statistics. Bone Marrow Transpl. 2013;48:452–8.

    Article  CAS  Google Scholar 

  20. Schanz J, Tüchler H, Solé F, Mallo M, Luño E, Cervera J, et al. New comprehensive cytogenetic scoring system for primary myelodysplastic syndromes (MDS) and oligoblastic acute myeloid leukemia after MDS derived from an international database merge. J Clin Oncol. 2012;30:820–9.

    Article  Google Scholar 

  21. Grimwade D, Walker H, Oliver F, Wheatley K, Harrison C, Harrison G, et al. The importance of diagnostic cytogenetics on outcome in AML: analysis of 1,612 patients entered into the MRC AML 10 trial. The Medical Research Council Adult and Children’s Leukaemia Working Parties. Blood 1998;92:2322–33.

    Article  CAS  Google Scholar 

  22. Ding L, Ley TJ, Larson DE, Miller CA, Koboldt DC, Welch JS, et al. Clonal evolution in relapsed acute myeloid leukaemia revealed by whole-genome sequencing. Nature 2012;481:506–10.

    Article  CAS  Google Scholar 

  23. Willers H, Dahm-Daphi J, Powell SN. Repair of radiation damage to DNA. Br J Cancer. 2004;90:1297–301.

    Article  CAS  Google Scholar 

  24. Samoylov AS, Bushmanov AY, Udalov YD, Galstyan IA, Nugis VY, Kozlova MG, et al. Acute myeloid leukemia, prostate and skin cancer in acute radiation syndrome survivor after the 1986 chernobyl nuclear accident: Case report. Radiat Prot Dosim. 2018;182:85–9.

    Article  CAS  Google Scholar 

  25. Nagayama H, Misawa K, Tanaka H, Ooi J, Iseki T, Tojo A, et al. Transient hematopoietic stem cell rescue using umbilical cord blood for a lethally irradiated nuclear accident victim. Bone Marrow Transpl. 2002;29:197–204.

    Article  CAS  Google Scholar 

  26. Awa AA, Sofuni T, Honda T, Itoh M, Neriishi S, Otake M. Relationship between the radiation dose and chromosome aberrations in atomic bomb survivors of Hiroshima and Nagasaki. J Radiat Res. 1978;19:126–40.

    Article  CAS  Google Scholar 

  27. Sloand EM, Pfannes L, Ling C, Feng X, Jasek M, Calado R, et al. Graft-versus-host disease: Role of inflammation in the development of chromosomal abnormalities of keratinocytes. Biol Blood Marrow Transpl. 2010;16:1665–73.

    Article  CAS  Google Scholar 

  28. Vago L, Perna SK, Zanussi M, Mazzi B, Barlassina C, Stanghellini MT, et al. Loss of mismatched HLA in leukemia after stem-cell transplantation. N. Engl J Med. 2009;361:478–88.

    Article  CAS  Google Scholar 

  29. Papaemmanuil E, Gerstung M, Bullinger L, Gaidzik VI, Paschka P, Roberts ND, et al. Genomic classification and prognosis in acute myeloid leukemia. N. Engl J Med. 2016;374:2209–21.

    Article  CAS  Google Scholar 

  30. Schmidt-Hieber M, Blau IW, Richter G, Türkmen S, Bommer C, Thiel G, et al. Cytogenetic studies in acute leukemia patients relapsing after allogeneic stem cell transplantation. Cancer Genet Cytogenet. 2010;198:135–43.

    Article  CAS  Google Scholar 

  31. Garson OM, Hagemeijer A, Sakurai M, Reeves BR, Swansbury GJ, Williams GJ, et al. Cytogenetic studies of 103 patients with acute myelogenous leukemia in relapse. Cancer Genet Cytogenet. 1989;40:187–202.

    Article  CAS  Google Scholar 

  32. Waisertreiger I, Barlow J. Fragile site instability: Measuring more than breaks. Oncoscience 2020;7:60–7.

    Article  Google Scholar 

  33. Arlt MF, Durkin SG, Ragland RL, Glover TW. Common fragile sites as targets for chromosome rearrangements. DNA Repair (Amst). 2006;5:1126–35.

    Article  CAS  Google Scholar 

  34. Patel JP, Gönen M, Figueroa ME, Fernandez H, Sun Z, Racevskis J, et al. Prognostic relevance of integrated genetic profiling in acute myeloid leukemia. N. Engl J Med. 2012;366:1079–89.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

We would like to thank donors, recipients, and physicians for their contributions.

Author information

Authors and Affiliations

  1. Division of Hematology, Jichi Medical University Saitama Medical Center, Saitama, Japan

    Yosuke Okada, Hideki Nakasone, Yuhei Nakamura, Masakatsu Kawamura, Shunto Kawamura, Junko Takeshita, Nozomu Yoshino, Yukiko Misaki, Kazuki Yoshimura, Shimpei Matsumi, Ayumi Gomyo, Yu Akahoshi, Machiko Kusuda, Kazuaki Kameda, Aki Tanihara, Masaharu Tamaki, Shun-ichi Kimura, Shinichi Kako & Yoshinobu Kanda

  2. Division of Hematology, Department of Internal Medicine, National Defense Medical College Hospital, Saitama, Japan

    Yosuke Okada, Toshikuni Kawamura, Shinichi Kobayashi & Fumihiko Kimura

Authors
  1. Yosuke Okada
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Hideki Nakasone
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Yuhei Nakamura
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Masakatsu Kawamura
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Shunto Kawamura
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Junko Takeshita
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Nozomu Yoshino
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Yukiko Misaki
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Kazuki Yoshimura
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Shimpei Matsumi
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Ayumi Gomyo
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Toshikuni Kawamura
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Yu Akahoshi
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Machiko Kusuda
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. Kazuaki Kameda
    View author publications

    You can also search for this author in PubMed Google Scholar

  16. Aki Tanihara
    View author publications

    You can also search for this author in PubMed Google Scholar

  17. Masaharu Tamaki
    View author publications

    You can also search for this author in PubMed Google Scholar

  18. Shun-ichi Kimura
    View author publications

    You can also search for this author in PubMed Google Scholar

  19. Shinichi Kobayashi
    View author publications

    You can also search for this author in PubMed Google Scholar

  20. Shinichi Kako
    View author publications

    You can also search for this author in PubMed Google Scholar

  21. Fumihiko Kimura
    View author publications

    You can also search for this author in PubMed Google Scholar

  22. Yoshinobu Kanda
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

YO designed the study, collected, and analyzed data, and wrote the manuscript. HN designed the study, analyzed data, and wrote the manuscript. YN, MK, S Kawamura, JT, NY, YM, KY, SM, AG, TK, YA, MK, KK, AT, MT, S Kimura, S Kobayashi, and S Kako collected clinical data. FK and YK advised on the methods, wrote the manuscript, and were responsible for the projects.

Corresponding author

Correspondence to Yoshinobu Kanda.

Ethics declarations

Competing interests

The authors declare no competing interests.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary information

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Okada, Y., Nakasone, H., Nakamura, Y. et al. Prognostic impact of chromosomal changes at relapse after allogeneic hematopoietic cell transplantation for acute myeloid leukemia or myelodysplastic syndrome. Bone Marrow Transplant 57, 810–816 (2022). https://doi.org/10.1038/s41409-022-01635-4

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41409-022-01635-4

Search

Advanced search

Quick links