Iron overload manifesting as apparent exacerbation of hepatic graft-versus-host disease after allogeneic hematopoietic stem cell transplantation

Biol Blood Marrow Transplant. 2006 May;12(5):506-10. doi: 10.1016/j.bbmt.2006.01.004.


Iron overload presenting as exacerbation of hepatic graft-versus-host disease (GVHD) after allogeneic hematopoietic stem cell transplantation has not been previously described. We report 6 patients with established hepatic GVHD in whom iron overload (median serum ferritin, 7231 mug/dL; median transferrin saturation, 77%) resulting from a lifetime median of 20 units of packed red blood cell transfusions was manifested by worsening of liver function. Liver biopsies performed in 4 patients confirmed severe iron overload and also hepatic GVHD. Analysis for the C282Y and H63D hemochromatosis gene mutation was negative for the homozygous state in all 6 patients. Erythropoietin-assisted phlebotomy resulted in normalization of liver function at a median of 7 months and of serum ferritin at a median of 11 months. Immunosuppressive therapy was successfully tapered in all 4 patients who completed the phlebotomy program, and this supported the impression that iron overload, rather than GVHD, was the principal cause of liver dysfunction. At a median follow-up of 50 months (range, 18-76 months) from the transplantation and 25 months (range, 5-36 months) from ferritin normalization, all 4 patients require maintenance phlebotomy. We conclude that iron overload can mimic GVHD exacerbation, thus resulting in unnecessary continuation or intensification of immunosuppressive therapy for GVHD, and that maintenance phlebotomy is necessary after successful iron-reduction therapy.

MeSH terms

  • Adult
  • Biopsy
  • Bone Marrow Transplantation / adverse effects
  • Combined Modality Therapy
  • Darbepoetin alfa
  • Diagnosis, Differential
  • Disease Progression
  • Epoetin Alfa
  • Erythrocyte Transfusion / adverse effects*
  • Erythropoietin / analogs & derivatives
  • Erythropoietin / therapeutic use
  • Female
  • Ferritins / blood
  • Graft vs Host Disease / diagnosis*
  • Graft vs Host Disease / drug therapy
  • Graft vs Host Disease / etiology
  • Hematopoietic Stem Cell Transplantation / adverse effects*
  • Humans
  • Immunosuppressive Agents / therapeutic use
  • Iron Overload / complications
  • Iron Overload / diagnosis*
  • Iron Overload / therapy
  • Liver Diseases / diagnosis*
  • Liver Diseases / etiology
  • Liver Diseases / pathology
  • Male
  • Middle Aged
  • Pancreatic Diseases / etiology
  • Phlebotomy
  • Prospective Studies
  • Recombinant Proteins
  • Skin Diseases / etiology
  • Transferrin / analysis
  • Transplantation Conditioning
  • Transplantation, Homologous / adverse effects*


  • Immunosuppressive Agents
  • Recombinant Proteins
  • Transferrin
  • Erythropoietin
  • Darbepoetin alfa
  • Epoetin Alfa
  • Ferritins