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.

  • Review Article
  • Published:

Donor-derived malignancy after allogeneic stem cell transplantation: a rare but well recognized complication

Bone Marrow Transplantation (2025)Cite this article

Subjects

Abstract

Relapse after allogeneic stem cell transplantation (allo-SCT) remains a major drawback of the procedure, occurring in approximately 30-60% of patients. While most relapses arise from the original malignant clone, they may also emerge from donor-derived cells harbouring genetic defects that confer a malignant phenotype. Although initially considered an exceedingly rare phenomenon, advances in molecular techniques for chimerism analysis have led to an increase in case reporting and awareness of donor-derived malignancy (DDM), with a rising estimated incidence. Differentiating between relapse of the original disease and DDM is critical, as they are associated with distinct treatment approaches and outcomes. In the case of DDM, there may also be significant ethical implications for the donor, with the dilemma of whether donors should be notified and whether high-risk donor populations – such as older individuals and those providing umbilical cord blood grafts – should be screened for germline mutations or clones of indeterminate potential prior to donation. Since the first report of a DDM case in 1971, 64 cases were reported through 2009. The aim of this study was to systematically review the literature and critically analyze the DDM cases reported from 2009 to 2024, identifying potential common characteristics that may predispose to DDM development.

Access through your institution
Buy or subscribe

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

Access options

Access through your institution

Buy this article

  • Purchase on SpringerLink
  • Instant access to full article PDF
Buy now

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

Fig. 1: Factors correlating with the time to DDM development.
Fig. 2: Cytogenetic abnormalities.
Fig. 3: Mutational screen.
Fig. 4: Overall Survival.

Similar content being viewed by others

Data availability

The data that support the findings of this study are available from the corresponding author upon reasonable request.

References

  1. Copelan EA. Hematopoietic stem-cell transplantation. N Engl J Med. 2006;354:1813–26.

    Article  CAS  PubMed  Google Scholar 

  2. Kumar L. Leukemia: management of relapse after allogeneic bone marrow transplantation. J Clin Oncol. 1994;12:1710–7.

    Article  CAS  PubMed  Google Scholar 

  3. Myron Kauffman H, McBride MA, Cherikh WS, Spain PC, Marks WH, Roza AM. Transplant tumor registry: donor related malignancies. Transplantation. 2002;74:358–62.

    Article  CAS  PubMed  Google Scholar 

  4. Horowitz M, Schreiber H, Elder A, Heidenreich O, Vormoor J, Toffalori C, et al. Epidemiology and biology of relapse after stem cell transplantation. Bone Marrow Transpl. 2018;53:1379–89.

    Article  CAS  Google Scholar 

  5. Giralt SA, Champlin RE. Leukemia relapse after allogeneic bone marrow transplantation: a review. Blood. 1994;84:3603–12.

    Article  CAS  PubMed  Google Scholar 

  6. Williams LS, Williams KM, Gillis N, Bolton K, Damm F, Deuitch NT, et al. Donor-derived malignancy and transplantation morbidity: risks of patient and donor genetics in allogeneic hematopoietic stem cell transplantation. Transplant Cell Ther. 2024;30:255–67.

    Article  CAS  PubMed  Google Scholar 

  7. Kato M, Yamashita T, Suzuki R, Matsumoto K, Nishimori H, Takahashi S, et al. Donor cell-derived hematological malignancy: a survey by the Japan Society for Hematopoietic Cell Transplantation. Leukemia. 2016;30:1742–5.

    Article  CAS  PubMed  Google Scholar 

  8. Hertenstein B, Hambach L, Bacigalupo A, Schmitz N, McCann S, Slavin S, et al. Development of leukemia in donor cells after allogeneic stem cell transplantation-a survey of the European Group for Blood and Marrow Transplantation (EBMT). Haematologica. 2005;90:969–75.

    PubMed  Google Scholar 

  9. Wiseman DH. Donor cell leukemia: a review. Biol Blood Marrow Transpl. 2011;17:771–89.

    Article  Google Scholar 

  10. Atsuta Y, Baldomero H, Neumann D, Sureda A, DeVos JD, Iida M, et al. Continuous and differential improvement in worldwide access to hematopoietic cell transplantation: activity has doubled in a decade with a notable increase in unrelated and non-identical related donors. Haematologica. 2024;109:3282–94.

    Article  PubMed  PubMed Central  Google Scholar 

  11. Niederwieser D, Baldomero H, Bazuaye N, Bupp C, Chaudhri N, Corbacioglu S, et al. One and a half million hematopoietic stem cell transplants: continuous and differential improvement in worldwide access with the use of non-identical family donors. Haematologica. 2022;107:1045–53.

    Article  PubMed  Google Scholar 

  12. Tokaz MC, Baldomero H, Cowan AJ, Saber W, Greinix H, Koh MBC, et al. An Analysis of the Worldwide Utilization of Hematopoietic Stem Cell Transplantation for Acute Myeloid Leukemia. Transplant Cell Ther. 2023;29:279.e1–e10.

    Article  PubMed  Google Scholar 

  13. Penack O, Peczynski C, Mohty M, Yakoub-Agha I, Styczynski J, Montoto S, et al. How much has allogeneic stem cell transplant-related mortality improved since the 1980s? A retrospective analysis from the EBMT. Blood Adv. 2020;4:6283–90.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Gratwohl A, Pasquini MC, Aljurf M, Atsuta Y, Baldomero H, Foeken L, et al. One million haemopoietic stem-cell transplants: a retrospective observational study. Lancet Haematol. 2015;2:e91–100.

    Article  PubMed  Google Scholar 

  15. Zuanelli Brambilla C, Lobaugh SM, Ruiz JD, Dahi PB, Goldberg AD, Young JW, et al. Relapse after allogeneic stem cell transplantation of acute myelogenous leukemia and myelodysplastic syndrome and the importance of second cellular therapy. Transplant Cell Ther. 2021;27:771.e1–e10.

    Article  CAS  PubMed  Google Scholar 

  16. Socie G, Stone JV, Wingard JR, Weisdorf D, Henslee-Downey PJ, Bredeson C, et al. Long-term survival and late deaths after allogeneic bone marrow transplantation. Late Effects Working Committee of the International Bone Marrow Transplant Registry. N Engl J Med. 1999;341:14–21.

    Article  CAS  PubMed  Google Scholar 

  17. Bejanyan N, Weisdorf DJ, Logan BR, Wang HL, Devine SM, de Lima M, et al. Survival of patients with acute myeloid leukemia relapsing after allogeneic hematopoietic cell transplantation: a center for international blood and marrow transplant research study. Biol Blood Marrow Transpl. 2015;21:454–9.

    Article  Google Scholar 

  18. Antier C, Jullien M, Tessoulin B, Loirat M, Peterlin P, Garnier A, et al. Late relapse after allogeneic stem cell transplantation in patients treated for acute myeloid leukemia: relapse incidence, characteristics, role of conditioning regimen, and outcome. Cancers. 2024;16:1419.

  19. Engel N, Rovo A, Badoglio M, Labopin M, Basak GW, Beguin Y, et al. European experience and risk factor analysis of donor cell-derived leukaemias/MDS following haematopoietic cell transplantation. Leukemia. 2019;33:508–17.

    Article  CAS  PubMed  Google Scholar 

  20. Musiu P, Quattrocchi L, Barberi W, Della Starza I, Elia L, De Novi LA, et al. Donor cell derived mantle cell lymphoma in a HSCT sibling donor-recipient pair: intrinsic biological clock in lymphomagenesis. Leuk Lymphoma. 2022;63:499–502.

    Article  CAS  PubMed  Google Scholar 

  21. Otero L, de Souza DC, de Cassia Tavares R, Gomes BE, Padilha TF, Bouzas LF, et al. Monosomy 7 in donor cell-derived leukemia after bone marrow transplantation for severe aplastic anemia: Report of a new case and review of the literature. Genet Mol Biol. 2012;35:734–6.

    Article  PubMed  PubMed Central  Google Scholar 

  22. Deshmukh KG, Kelemen K. Lessons learned from donor cell-derived myeloid neoplasms: report of three cases and review of the literature. Life. 2022;12:559.

  23. Jaiswal S, Ebert BL. Clonal hematopoiesis in human aging and disease. Science. 2019;366:eaan4673.

  24. Gibson CJ, Kim HT, Zhao L, Murdock HM, Hambley B, Ogata A, et al. Donor clonal hematopoiesis and recipient outcomes after transplantation. J Clin Oncol. 2022;40:189–201.

    Article  CAS  PubMed  Google Scholar 

  25. Kennedy AL, Shimamura A. Genetic predisposition to MDS: clinical features and clonal evolution. Blood. 2019;133:1071–85.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Halik A, Tilgner M, Silva P, Estrada N, Altwasser R, Jahn E, et al. Genomic characterization of AML with aberrations of chromosome 7: a multinational cohort of 519 patients. J Hematol Oncol. 2024;17:70.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Lindsley RC, Mar BG, Mazzola E, Grauman PV, Shareef S, Allen SL, et al. Acute myeloid leukemia ontogeny is defined by distinct somatic mutations. Blood. 2015;125:1367–76.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Marchionni L, Lobo FP, Kostadinov R, Serra A, Besso FG, Deaglio S, et al. Donor-derived acute myeloid leukemia in solid organ transplantation. Am J Transpl. 2022;22:3111–9.

    Article  Google Scholar 

  29. Babushok DV, Bessler M, Olson TS. Genetic predisposition to myelodysplastic syndrome and acute myeloid leukemia in children and young adults. Leuk Lymphoma. 2016;57:520–36.

    Article  CAS  PubMed  Google Scholar 

  30. Suarez-Gonzalez J, Martinez-Laperche C, Kwon M, Balsalobre P, Carbonell D, Chicano M, et al. Donor Cell-Derived Hematologic neoplasms after hematopoietic stem cell transplantation: a systematic review. Biol Blood Marrow Transpl. 2018;24:1505–13.

    Article  Google Scholar 

  31. Holyoake TL, Nicolini FE, Eaves CJ. Functional differences between transplantable human hematopoietic stem cells from fetal liver, cord blood, and adult marrow. Exp Hematol. 1999;27:1418–27.

    Article  CAS  PubMed  Google Scholar 

  32. Mori H, Colman SM, Xiao Z, Ford AM, Healy LE, Donaldson C, et al. Chromosome translocations and covert leukemic clones are generated during normal fetal development. Proc Natl Acad Sci USA. 2002;99:8242–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Greaves MF. Cord blood donor cell leukemia in recipients. Leukemia. 2006;20:1633–4.

    Article  CAS  PubMed  Google Scholar 

  34. Khattab A, Patruni S, Patrus G, Samhouri Y, Fazal S, Lister J. Donor cell leukemia following allogeneic hematopoietic stem cell transplantation. J Hematol. 2023;12:138–44.

    Article  PubMed  PubMed Central  Google Scholar 

  35. Frick M, Chan W, Arends CM, Hablesreiter R, Halik A, Heuser M, et al. Role of donor clonal hematopoiesis in allogeneic hematopoietic stem-cell transplantation. J Clin Oncol. 2019;37:375–85.

    Article  CAS  PubMed  Google Scholar 

  36. Kato M. [Donor cell-derived hematological malignancies after allogeneic hematopoietic stem cell transplantation]. Rinsho Ketsueki. 2017;58:813–7.

    PubMed  Google Scholar 

  37. Ogonek J, Kralj Juric M, Ghimire S, Varanasi PR, Holler E, Greinix H, et al. Immune reconstitution after allogeneic hematopoietic stem cell transplantation. Front Immunol. 2016;7:507.

    Article  PubMed  PubMed Central  Google Scholar 

  38. Palka G, Calabrese G, Di Girolamo G, Stuppia L, Di Bartolomeo P, Guanciali Franchi P, et al. Cytogenetic survey of 31 patients treated with bone marrow transplantation for acute nonlymphocytic and acute lymphoblastic leukemias. Cancer Genet Cytogenet. 1991;51:223–33.

    Article  CAS  PubMed  Google Scholar 

  39. Aldoss I, Song JY, Curtin PT, Forman SJ. Multiple donor-derived leukemias in a recipient of allogeneic hematopoietic cell transplantation for myeloid malignancy. Blood Adv. 2020;4:4798–801.

    Article  PubMed  PubMed Central  Google Scholar 

  40. Kurosawa S, Doki N, Hino Y, Sakaguchi M, Fukushima K, Shingai N, et al. Occurrence of donor cell-derived lymphoid blast crisis 24 years following related bone marrow transplantation for chronic myeloid leukemia. Intern Med. 2016;55:395–7.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Hematology Department, Attikon General University Hospital, Athens, Greece

    Panagiotis Tsirigotis & Ioanna Lazana

  2. National and Kapodistrian University of Athens, Athens, Greece

    Panagiotis Tsirigotis

Authors
  1. Panagiotis Tsirigotis
    View author publications

    Search author on:PubMed Google Scholar

  2. Ioanna Lazana
    View author publications

    Search author on:PubMed Google Scholar

Contributions

PT: Formal analysis and writing, IL: Conceptualization, analysis, and editing writing.

Corresponding author

Correspondence to Ioanna Lazana.

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

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Tsirigotis, P., Lazana, I. Donor-derived malignancy after allogeneic stem cell transplantation: a rare but well recognized complication. Bone Marrow Transplant (2025). https://doi.org/10.1038/s41409-025-02725-9

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1038/s41409-025-02725-9

Search

Advanced search

Quick links