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Ruutu (Abstract)

Cellular Therapy and Transplantation (CTT), Vol. 3, No. 12
doi: 10.3205/ctt-2011-No12-abstract67

© The Authors. This abstract is provided under the following license: Creative Commons Attribution 3.0 Unported

Abstract accepted for "5th Raisa Gorbacheva Memorial Meeting Hematopoietic Stem Cell Transplantation in Children and Adults", Saint Petersburg, Russia, September 18–20, 2011

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The role of iron load in the outcome of allogeneic transplantation

Tapani Ruutu

Department of Medicine, Division of Haematology, Helsinki University Central Hospital, Helsinki, Finland

Correspondence: Tapani Ruutu, Department of Medicine, Division of Haematology, Helsinki University Central Hospital, Biomedicum 2 C, POB 705, Helsinki University Central Hospital, FIN-00029 HUS, Helsinki, Finland, E-mail: tapani.ruutu@spam is badhus.fi

Abstract

Iron overload is very common in patients undergoing allogeneic hematopoietic stem cell transplantation. Many patients have received blood transfusions in earlier therapy, and the absorption of iron from the gut may be excessive due to the underlying disease such as myelodysplastic syndrome or thalassemia. The metabolism and distribution of iron in the body are altered during allogeneic transplantation. The underlying disease, for example myelodysplastic syndrome, may cause ineffective erythropoiesis resulting in underutilization of iron pools. The conditioning treatment causes cessation of hematopoiesis and utilization of iron. The cytotoxic effects of chemo/radiotherapy also affect other organs, including the liver, which may lead to iron release through hepatocellular injury and to disturbed transferrin synthesis. The concomitant release of iron and decrease in the transferrin concentration lead to an increase in transferrin saturation. When the saturation exceeds 80%, free non-transferrin-bound iron (NTBI) usually appears in the serum. Almost all allogeneic transplant recipients who have received a myeloablative conditioning have demonstrable NTBI in the serum for up to two weeks after the transplantation. Reactive oxygen species catalyzed by NTBI can cause cellular damage through several mechanisms and, thus, be one of the contributing factors in the therapy-related complications of allogeneic transplantation. For example, mucositis and liver irritation (increased transaminase levels) caused by the conditioning have been suggested to represent, at least to some extent, the detrimental effects of NTBI. Hyperferremia is also known to predispose to bacterial and fungal infections. There have also been reports suggesting a role for iron toxicity in veno-occlusive disease of the liver, graft versus host disease, and idiopathic pneumonia. 

Serum ferritin is used as the main measure of iron stores, and many studies have shown its prognostic significance. Patients with high serum ferritin before allogeneic transplantation have been shown to have an impaired prognosis. Although ferritin reflects relatively well the iron status, other factors, especially inflammation and autoimmune phenomena, also affect its serum levels. Thus, graft versus host disease can affect the ferritin concentrations. Other methods, such as magnetic resonance imaging (MRI) of the liver or liver biopsy, may therefore be needed to confirm iron overload. Other serum iron parameters have also been studied, and both soluble transferrin receptor and transferrin saturation have been found to be useful indicators of iron load and to have prognostic value.

As iron overload has been shown to be an adverse prognostic factor in allogeneic transplantation, removal of excess iron before the transplantation would be likely to improve the outcome, although prospective studies to demonstrate this are needed. At one year after the transplantation a majority of patients have high serum ferritin levels, but, in addition to iron overload, other factors are likely to contribute to this finding. However, post-transplant removal of iron would seem to be indicated in many cases. Effective removal of iron is often difficult. Phlebotomy is in principle a preferable method but it can be rarely applied before the transplantation as most patients are anemic. It can be used when erythropoiesis has fully recovered after the transplantation. With the availability of oral chelating agents, iron chelation has become more feasible than before. How oral chelators would be best used in practice needs more investigation. Substantial removal of iron with chelating agents takes a considerable time, which is available only for a limited proportion of patients before the transplantation. Chelators can be used after the transplantation but they should be used with caution because of their potential renal, gastrointestinal, hepatic, and hematological side effects. Binding free iron with apotransferrin during the conditioning and the aplastic phase after the transplantation is a theoretically promising approach.

Keywords: allogeneic hematopoietic stem cell transplantation, iron overload