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.

  • Original Article
  • Published:

Inherited and Genetic Disorders

Secondary solid cancer following hematopoietic cell transplantation in patients with thalassemia major

Abstract

Hematopoietic cell transplant (HCT) recipients have a substantial risk of developing secondary solid cancers (SSCs). The aim of this retrospective study was to compare the incidence of SSC in a monocentric cohort of thalassemia major (TM) patients (n=122) who received HCT versus an hematopoietic cell donor monocentric cohort (n=122) and versus a large multicenter cohort of age- and sex-matched TM patients (n=244) who received conventional therapy. With a median follow-up of 24 years, 8 transplanted patients were diagnosed with SSC at a median of 18 years after HCT and at a median age of 33 years. Three patients died of cancer progression and 5 are living after a follow-up ranging from 10 months to 16 years after SSC diagnosis. The 30-year cumulative incidence of developing SSC was 13.24%. The occurrence of solid cancers in the hematopoietic cell donor cohort was limited to only one case for a significantly lower cumulative incidence (3.23%, P=0.02) and to 3 cases in the cohort of nontransplant patients for a significantly lower cumulative incidence (1.32%, P=0.005). This study shows that the magnitude of increased risk of SST is fourfold to sixfold for patients treated with HCT as compared with hematopoietic cell donors and nontransplant patients.

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

Access options

Buy this article

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

Figure 1

Similar content being viewed by others

References

  1. Rachmilewitz E, Giardina PJ . How I treat thalassemia. Blood 2011; 118: 3479–3488.

    Article  CAS  Google Scholar 

  2. Meloni A, Positano V, Ruffo GB, Spasiano A, D’Ascola DG, Peluso A et al. Improvement of heart iron with preserved patterns of iron store by CMR-guided chelation therapy. Eur Heart J Cardiovasc Imaging 2015; 16: 325–334.

    Article  Google Scholar 

  3. Pepe A, Meloni A, Rossi G, Midiri M, Missere M, Valeri G et al. Prediction of cardiac complications for thalassemia major in the widespread cardiac magnetic resonance era: a prospective multicenter study by a multi-parametric approach. Eur Heart J Cardiovasc Imaging, (e-pub ahead of print 14 February 2017; doi: 10.1093/ehjci/jex012).

    Article  Google Scholar 

  4. Borgna-Pignatti C, Rugolotto S, De Stefano P, Zhao H, Cappellini MD, Del Vecchio GC et al. Survival and complications in patients with thalassemia major treated with transfusion and deferoxamine. Haematologica 2004; 89: 1187–1193.

    PubMed  Google Scholar 

  5. Zanella S, Garani MC, Borgna-Pignatti C . Malignancies and thalassemia: a review of the literature. Ann NY Acad Sci 2016; 1368: 140–148.

    Article  Google Scholar 

  6. Angelucci E, Matthes-Martin S, Baronciani D, Bernaudin F, Bonanomi S, Cappellini MD et al. Hematopoietic stem cell transplantation in thalassemia major and sickle cell disease: indications and management recommendations from an international expert panel. Haematologica 2014; 99: 811–820.

    Article  Google Scholar 

  7. Higgs DR, Engel JD, Stamatoyannopoulos G . Thalassaemia. Lancet 2012; 379: 373–383.

    Article  CAS  Google Scholar 

  8. Lucarelli G, Gaziev J . Advances in the allogeneic transplantation for thalassemia. Blood Rev 2008; 22: 53–63.

    Article  Google Scholar 

  9. Bhatia S, Louie AD, Bhatia R, O'Donnell MR, Fung H, Kashyap A et al. Solid cancers after bone marrow transplantation. J Clin Oncol 2001; 19: 464–471.

    Article  CAS  Google Scholar 

  10. Meloni A, Ramazzotti A, Positano V, Salvatori C, Mangione M, Marcheschi P et al. Evaluation of a web-based network for reproducible T2* MRI assessment of iron overload in thalassemia. Int J Med Inform 2009; 78: 503–512.

    Article  CAS  Google Scholar 

  11. Di Bartolomeo P, Santarone S, Di Bartolomeo E, Olioso P, Bavaro P, Papalinetti G et al. Long-term results of survival in patients with thalassemia major treated with bone marrow transplantation. Am J Hematol 2008; 83: 528–530.

    Article  Google Scholar 

  12. Ishak K, Baptista A, Bianchi L, Callea F, De Groote J, Gudat F et al. Histological grading and staging of chronic hepatitis. J Hepatol 1995; 22: 696–699.

    Article  CAS  Google Scholar 

  13. Modell B, Khan M, Darlison M, Westwood MA, Ingram D, Pennell DJ et al. Improved survival of thalassaemia major in the UK and relation to T2* cardiovascular magnetic resonance. J Cardiovasc Magn Reson 2008; 10: 42–50.

    Article  Google Scholar 

  14. Telfer PT, Warburton F, Christou S, Hadjigavriel M, Sitanou M, Kolnagou A et al. Improved survival in thalassemia major patients on switching from desferioxamine to combined chelation therapy with desferioxamine and deferiprone. Haematologica 2009; 94: 1777–1778.

    Article  Google Scholar 

  15. Rizzo JD, Curtis RE, Sociè G, Sobocinski KA, Gilbert E, Landgren O et al. Solid cancers after allogeneic hematopoietic cell transplantation. Blood 2009; 113: 1175–1183.

    Article  CAS  Google Scholar 

  16. Curtis RE, Rowlings PA, Deeg HJ, Shriner DA, Socíe G, Travis LB et al. Solid cancers after bone marrow transplantation. N Engl J Med 1997; 336: 897–904.

    Article  CAS  Google Scholar 

  17. Sociè G, Henry-Amar M, Bacigalupo A, Hows J, Tichelli A, Ljungman P et al. Malignant tumors occurring after treatment of aplastic anemia. N Engl J Med 1993; 329: 1152–1157.

    Article  Google Scholar 

  18. Baker KS, DeFor TE, Burns LJ, Ramsay NK, Neglia JP, Robison LL . New malignancies after blood or marrow stem-cell transplantation in children and adults: incidence and risk factors. J Clin Oncol 2003; 21: 1352–1358.

    Article  Google Scholar 

  19. Ringden O, Brazauskas R, Wang Z, Ahmed I, Atsuta Y, Buchbinder D et al. Second solid cancers after allogeneic hematopoietic cell transplantation using reduced intensity conditioning. Biol Blood Marrow Transplant 2014; 20: 1777–1784.

    Article  Google Scholar 

  20. Lowe T, Bathia S, Somio G . Second malignancies after allogeneic hematopoietic cell transplantation. Biol Blood Marrow Transplant 2007; 13: 1121–1134.

    Article  Google Scholar 

  21. Borgna-Pignatti C, Garani MC, Forni GL, Cappellini MD, Cassinerio E, Fidone C et al. Hepatocellular carcinoma in thalassaemia: an update of the Italian Registry. Br J Haematol 2014; 167: 121–126.

    Article  CAS  Google Scholar 

  22. Karimi M, Giti R, Haghpanah S, Azarkeivan A, Hoofar H, Eslami M . Malignancies in patients with beta-thalassemia major and beta-thalassemia intermedia: a multicenter study in Iran. Pediatr Blood Cancer 2009; 53: 1064–1067.

    Article  Google Scholar 

  23. Stevens RG, Jones DY, Micozzi MS, Taylor PR . Body iron stores and the risk of cancer. N Engl J Med 1988; 319: 1047–1052.

    Article  CAS  Google Scholar 

  24. Maakaron JE, Cappellini MD, Graziadei G, Ayache JB, Taher AT . Hepatocellular carcinoma in hepatitis-negative patients with thalassemia intermedia: a closer look at the role of siderosis. Ann Hepatol 2013; 12: 142–146.

    PubMed  Google Scholar 

  25. Inamoto Y, Shan NN, Savani BN, Shaw BE, Abraham AA, Ahmed IA et al. Secondary solid cancer screening following hematopoietic cell transplantation. Bone Marrow Transplant 2015; 50: 1013–1023.

    Article  CAS  Google Scholar 

  26. Sociè G, Rizzo JD . Second solid tumors: screening and management guidelines in long-term survivors after allogeneic stem cell transplantation. Semin Hematol 2012; 49: 4–9.

    Article  Google Scholar 

Download references

Acknowledgements

Author contributions

SS and PDB contributed patients, designed the study, analyzed the data and wrote the manuscript; AP and AM contributed patients, performed statistical study and contributed to the interpretation of the results; AN, PO, GP, LC, AS, RL, MDI, PA and TB contributed patients and critically reviewed the manuscript; LP was responsible for data collection; SS and SA performed statistical study; FP performed HLA typing.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to P Di Bartolomeo.

Ethics declarations

Competing interests

The authors declare no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Santarone, S., Pepe, A., Meloni, A. et al. Secondary solid cancer following hematopoietic cell transplantation in patients with thalassemia major. Bone Marrow Transplant 53, 39–43 (2018). https://doi.org/10.1038/bmt.2017.214

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/bmt.2017.214

This article is cited by

Search

Quick links