Skip to main content

Chronic myeloid leukemia in solid organ transplant patients: a case series

Abstract

Solid organ transplant (SOT) has transformed the survival and quality of life of patients with end-organ dysfunction. Lifelong need for immunosuppressive medications prolongs life expectancy, but results in altered immune function and is associated with a higher risk of certain malignancies, including chronic myeloid leukemia (CML). In this article, we report on six patients, aged 41–79 years, diagnosed with CML, from 3 to 132 months post-various organ transplants and treated with different tyrosine kinase inhibitors (TKI), including first generation (i.e., imatinib) and second generation (i.e., dasatinib and nilotinib). Use of second-generation TKIs has not been previously reported in this population. In these six cases, treatment with different TKIs in SOT patients was feasible, well tolerated and achieved good efficacy, which was maintained in extended follow-up, as well.

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

References

  1. Petrara MR, Giunco S, Serraino D, Dolcetti R, De Rossi A. Post-transplant lymphoproliferative disorders: from epidemiology to pathogenesis-driven treatment. Cancer Lett. 2015;369(1):37–44.

    CAS  Article  Google Scholar 

  2. Annual data report of the US Organ Procurement and Transplantation Network (OPTN) and the Scientific Registry of Transplant Recipients (SRTR). 2018 Annual Data Report: Preface. Am J Transplant. 2020;20 Suppl s1:1–10

  3. Grulich AE, van Leeuwen MT, Falster MO, Vajdic CM. Incidence of cancers in people with HIV/AIDS compared with immunosuppressed transplant recipients: a meta-analysis. Lancet. 2007;370(9581):59–67.

    Article  Google Scholar 

  4. Engels EA, Pfeiffer RM, Fraumeni JF Jr, Kasiske BL, Israni AK, Snyder JJ, et al. Spectrum of cancer risk among US solid organ transplant recipients. JAMA. 2011;306(17):1891–901.

    CAS  Article  Google Scholar 

  5. Piselli P, Verdirosi D, Cimaglia C, Busnach G, Fratino L, Ettorre GM, et al. Epidemiology of de novo malignancies after solid-organ transplantation: immunosuppression, infection and other risk factors. Best Pract Res Clin Obstet Gynaecol. 2014;28(8):1251–65.

    Article  Google Scholar 

  6. Wu B, Ingersoll K, Jug R, Yang LH, Luedke C, Lo A, et al. Myeloid neoplasms following solid organ transplantation: clinicopathologic studies of 23 cases. Am J Clin Pathol. 2017;149(1):55–66.

    Article  Google Scholar 

  7. Battin J, Hehunstre JP, Bui NB, Auzerie J, Colle M. Chronic myeloid leukaemia after immunosuppressive treatment for chronic nephropathy. Nouv Presse Med. 1976;5:2632.

    CAS  PubMed  Google Scholar 

  8. Morton LM, Gibson TM, Clarke CA, Lynch CF, Anderson LA, et al. Risk of myeloid neoplasms after solid organ transplantation. Leukemia. 2014;28(12):2317–23.

    CAS  Article  Google Scholar 

  9. le Coutre P, Reinke P, Neuhaus R, Trappe R, Ringel F, Lalancette M, et al. BCR-ABL positive cells and chronic myeloid leukemia in immune suppressed organ transplant recipients. Eur J Haematol. 2010;84(1):26–33.

    Article  Google Scholar 

  10. Jabbour E, Kantarjian H. Chronic myeloid leukemia: 2020 update on diagnosis, therapy and monitoring. Am J Hematol. 2020;95(6):691–709.

    CAS  Article  Google Scholar 

  11. Ayvazoglu Soy EH, Akdur A, Kirnap M, Boyvat F, Moray G, Haberal M. Vascular complications after renal transplant: a single-center experience. Exp Clin Transplant. 2017;15(Suppl 1):79–83.

    PubMed  Google Scholar 

  12. Hochhaus A, Larson RA, Guilhot F, Radich JP, Branford S, Hughes TP, IRIS Investigators, et al. Long-term outcomes of imatinib treatment for chronic myeloid leukemia. N Engl J Med. 2017;376(10):917–27.

    CAS  Article  Google Scholar 

  13. Guru Murthy GS, Atallah E. Treatment-free remission in CML: the US Perspective. Curr Hematol Malig Rep. 2019;14(1):56–61.

    Article  Google Scholar 

  14. Bocchia M, Wentworth PA, Southwood S, Sidney J, McGraw K, Scheinberg DA, et al. Specific binding of leukemia oncogene fusion protein peptides to HLA class I molecules. Blood. 1995;85(10):2680–4.

    CAS  Article  Google Scholar 

  15. Posthuma EF, Falkenburg JH, Apperley JF, Gratwohl A, Roosnek E, Hertenstein B, et al. HLA-B8 and HLA-A3 coexpressed with HLA-B8 are associated with a reduced risk of the development of chronic myeloid leukemia. The Chronic Leukemia Working Party of the EBMT. Blood. 1999;93(11):3863–5.

    CAS  PubMed  Google Scholar 

  16. Huang W, Liu B, Eklund EA. Investigating the role of the innate immune response in relapse or blast crisis in chronic myeloid leukemia. Leukemia. 2020;34(9):2364–2374.

    Article  Google Scholar 

  17. Bose S, Deininger M, Gora-Tybor J, Goldman JM, Melo JV. The presence of typical and atypical BCR-ABL fusion genes in leukocytes of normal individuals: biologic significance and implications for the assessment of minimal residual disease. Blood. 1998;92(9):3362–7.

    CAS  Article  Google Scholar 

  18. Marmont AM. The graft versus leukemia (GVL) effect after allogeneic bone marrow transplantation for chronic myelogenous leukemia (CML). Leuk Lymphoma. 1993;11(Suppl 1):221–6.

    Article  Google Scholar 

  19. Chan O, Talati C, Sweet K, Pinilla-Ibarz J. Can increased immunogenicity in chronic myeloid leukemia improve outcomes? Expert Rev Hematol. 2019;12(4):225–33.

    CAS  Article  Google Scholar 

  20. Dhanarajan A, Hsu JW, le Coutre P, Wingard JR, Chang M, Norkin M. Elevated incidence of chronic myeloid leukaemia in immunosuppressed solid organ transplant recipients. Br J Haematol. 2014;166(4):619–21.

    Article  Google Scholar 

  21. Tian T, Li X, Zhang J. mTOR signaling in cancer and mTOR inhibitors in solid tumor targeting therapy. Int J Mol Sci. 2019;20(3):755.

    CAS  Article  Google Scholar 

  22. Phan K, Moloney FJ, Hogarty DT, Lenane P, McColl D, Yazdabadi A. Mammalian target of rapamycin (mTOR) inhibitors and skin cancer risk in nonrenal solid organ transplant recipients: systematic review and meta-analysis. Int J Dermatol. 2019. https://doi.org/10.1111/ijd.14549.

    Article  PubMed  Google Scholar 

  23. Ilander M, Olsson-Strömberg U, Schlums H, Guilhot J, Brück O, Lähteenmäki H, et al. Increased proportion of mature NK cells is associated with successful imatinib discontinuation in chronic myeloid leukemia. Leukemia. 2017;31(5):1108–16.

    CAS  Article  Google Scholar 

  24. Hughes A, Clarson J, Tang C, Vidovic L, White DL, Hughes TP, et al. CML patients with deep molecular responses to TKI have restored immune effectors and decreased PD-1 and immune suppressors. Blood. 2017;129(9):1166–76.

    CAS  Article  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Contributions

All authors have contributed to the writing of this paper.

Corresponding author

Correspondence to Irina Amitai.

Ethics declarations

Conflict of interest

The authors have no financial conflict of interest to declare.

Ethical approval

No institutional or national ethical committee approval was needed. Every effort was made to preserve the patient’s confidentiality.

Additional information

Publisher's Note

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

About this article

Verify currency and authenticity via CrossMark

Cite this article

Amitai, I., Abulafia, A.S., Raanani, P. et al. Chronic myeloid leukemia in solid organ transplant patients: a case series. Int J Hematol 113, 214–218 (2021). https://doi.org/10.1007/s12185-020-03014-5

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12185-020-03014-5

Keywords

  • Chronic myeloid leukemia
  • Solid organ transplant
  • Imatinib
  • Dasatinib
  • Nilotinib