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.

  • Letter to the Editor
  • Published:

Iron-overload in long-term survivors of hematopoietic transplantation

Bone Marrow Transplantation volume 37, pages 805–806 (2006)Cite this article

In the February 2006 issue of Bone Marrow Transplantation, Rizzo et al.1 outline the recommendations for screening and preventive practices for long-term survivors. As described, iron overload in long-term transplant survivors has not been studied extensively. Consensus is lacking regarding the definition, incidence, clinical significance, diagnostic criteria and therapy for this disorder. In adults, transfusion-associated iron overload generally occurs after infusion of 100–150 U of packed red cells (PRBCs) (the equivalent of 25–40 g of elemental iron).2 However, in autologus and allogeneic hematopoietic transplant recipients, iron overload has been reported with infusion of less than 50–60 U of PRBCs.3, 4, 5, 6 Increased intestinal iron absorption in these is likely related to aberrant hepcidin regulation, although in the past, chemotherapy or graft-versus-host disease (GVHD) related intestinal epithelial injury was implicated.6, 7 Apart from its harmful effects on organ function (liver, heart, endocrine organs), iron overload can also result in worsening of viral hepatitis and its response to therapy, worsening of hepatic GVHD, and increased risk of opportunistic infections (Yersinia enterocolitica, Vibrio vulnificans, Listeria monocytogenes, Aspergillosis and Mucormycoses).4, 6, 8, 9, 10

Hyperferritinemia is a common late effect of hematopoietic transplantation.3 Although serum ferritin level does not correctly reflect body iron stores in all clinical circumstances, the combination of elevated ferritin with elevated transferrin saturation accurately identifies patients with increased body iron stores.8 At 1 year post transplant, when inflammatory stress has largely subsided, most patients have a serum ferritin of <1000 μg/dL and no clinical evidence of iron-overload; serum ferritin in these patients declines slowly with time.9 In another group of patients, however, issues such as viral hepatitis (25–50% incidence in some series) and GVHD affect both liver function tests and serum ferritin,3, 4 and confound the diagnosis of clinically significant iron overload. Jensen et al.,9 identified liver iron concentrations of 300–350 μ M/g as a critical level above which hepatocelluar injury, as reflected by aminotransferase elevation, was likely to occur. Both increased urinary iron excretion (>15 mg/24 h) and serum ferritin >1000 μg/dL (R2=0.55, P<0.0001) correlated with alanine aminotransferase elevation and high liver iron. Therefore, in the absence of data from liver biopsy, it appears that clinically significant iron overload does not occur until serum ferritin levels are greater than 1000 μg/dL.9

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

Relevant articles

Open Access articles citing this article.

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

References

  1. Rizzo JD, Wingard JR, Tichelli A, Lee SJ, Van Lint MT, Burns LJ et al. Recommended screening and preventive practices for long-term survivors after hematopoietic cell transplantation: joint recommendations of the European Group for Blood and Marrow Transplantation, Center for International Blood and Marrow Transplant Research, and the American Society for Blood and Marrow Transplantation (EBMT/CIBMTR/ASBMT). Bone Marrow Transplantation 2006; 37: 249–261.

    Article  CAS  PubMed  Google Scholar 

  2. Marcus RE, Huehns ER . Transfusional iron overload. Clini Lab Hematol 1985; 7: 195–212.

    Article  CAS  Google Scholar 

  3. McKay PJ, Murphy JA, Cameron S, Burnett AK, Campbell M, Tansey P et al. Iron overload and liver dysfunction after allogeneic or autologous bone marrow transplantation. Bone Marrow Transplant 1996; 17: 63–66.

    CAS  PubMed  Google Scholar 

  4. Tomas JF, Pinilla I, Garcia-Buey ML, Garcia A, Figuera A, Gomez-Garcia de Soria VGG et al. Long term liver dysfunction after allogeneic bone marrow transplantation: clinical features and course in 61 patients. Bone Marrow Transplant 2000; 26: 649–655.

    Article  CAS  PubMed  Google Scholar 

  5. Butt NM, Clark RE . Autografting as a risk factor for persisting iron overload in long terms survivors of acute leukemia. Bone Marrow Transplant 2003; 32: 909–913.

    Article  CAS  PubMed  Google Scholar 

  6. Kamble R, Selby S, Mims M, Kharfan-Dabaja M, Ozer H, George J . Iron overload manifesting as apparent exacerbation of hepatic graft-versus-host disease following allogeneic hematopoietic stem cell transplantation. Biol Bone Marrow Transplant 2006 (in press).

  7. Detivaud L, Nemeth E, Boudjema K, Turlin B, Troadec MB, Leroyer P et al. Hepcidin levels in humans are correlated with hepatic iron stores, hemoglobin levels, and hepatic function. Blood 2005; 106: 746–748.

    Article  CAS  PubMed  Google Scholar 

  8. Beutler E, Hoffbrand AV, Cook JD . Hematology iron deficiency and overload. Hematology (Am Soc Hematol Educ Program) 2003: 40–61.

    Article  Google Scholar 

  9. Jensen PD, Jensen FT, Christensen T, Nielsen JL, Ellegaard J . Relationship between hepatocellular injury and transfusion iron overload prior to and during iron chelation with desferrioxamine: a study in adult patients with acquired anemia. Blood 2003: 101: 91–96.

    Article  CAS  PubMed  Google Scholar 

  10. Ho GT, Parker AB, MacKenzie JF, Morris AJ, Stanley AJ . Abnormal liver function tests following bone marrow transplantation: Etiology and role of liver biopsy. Eur J Gastroenterol Hepatol 2004; 16: 157–162.

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. CAGT, Bone Marrow Transplant and Hematology-Oncology, Baylor College of Medicine, Houston, TX, USA

    R Kamble

  2. Hematology-Oncology, Baylor College of Medicine, Houston, TX, USA

    M Mims

Authors
  1. R Kamble
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. M Mims
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kamble, R., Mims, M. Iron-overload in long-term survivors of hematopoietic transplantation. Bone Marrow Transplant 37, 805–806 (2006). https://doi.org/10.1038/sj.bmt.1705335

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.bmt.1705335

This article is cited by

Search

Advanced search

Quick links