The role of iron in patients after bone marrow transplantation

doi:10.1016/S0268-960X(08)70005-5

Blood Reviews

Volume 22, Supplement 2, December 2008, Pages S22-S28

https://doi.org/10.1016/S0268-960X(08)70005-5 Get rights and content

Summary

Haemopoietic stem cell transplantation (HSCT) is an important intervention for malignant and non-malignant blood diseases. However, HSCT is also associated with considerable morbidity and mortality, some of which may be related to iron overload. Levels of serum iron are elevated in patients undergoing HSCT as a result of disturbed iron metabolism, pre-transplantation blood transfusions, or cytotoxic therapy for conditioning before HSCT. The complications of iron overload in HSCT patients include infections, mucositis, chronic liver disease (fibrosis progression), sinusoidal obstruction syndrome, and idiopathic pneumonia syndrome. Iron overload has an adverse impact on survival in patients undergoing HSCT for β-thalassaemia major or haematological malignancies including myelodysplastic syndromes. It has been suggested that all candidates for and all survivors of HSCT should be screened for iron overload at various time points before and after transplantation. Few studies of iron chelation therapy after HSCT have been reported, but one small study has indicated that deferoxamine is at least as effective as phlebotomy in reducing post-transplantation iron overload in patients with β-thalassaemia major. The new oral chelator deferasirox may be better tolerated than phlebotomy or deferoxamine infusion, and two prospective phase II studies in patients with iron overload after HSCT are now recruiting candidates.

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Cited by (37)

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2023, MacSween's Pathology of the Liver, Eighth Edition
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Allogeneic stem cell transplantation (allo-SCT) is the only currently available curative treatment for thalassemia major. Since it was first done in 1981, several thousand patients have benefited from it and it is now possible to offer this treatment in different parts of the world with good results. With better risk stratification and supportive care, the results of allo-SCT are now very good even in high risk patients who have significant iron overload related organ dysfunction. The improvements have mainly been in the conditioning strategies with less toxic myeloablation and management of the complications of SCT. However, several challenges remain. Transplant related complications still cause significant morbidity and mortality. There is data to show that the results of transplantation as best if done in well transfused and chelated patients <7 years of age. As only a third of the patients will have a matched related donor, there is need for investigating SCT with alternative donors. Experience with SCT for thalassemia major from matched unrelated donors or haplo-identical donors is still limited but needs further exploration. Adequate management needs to be provided post-SCT for all pre-existing complications particularly iron chelation to prevent further organ dysfunction. Systematic follow-up is needed to measure long term outcomes. The biggest challenges in India are the cost of this treatment and access to centres capable of providing this treatment. With greater support from the government, health insurance and philanthropic programs, there has been a rapid increase in the number of SCTs for thalassemia major in India. The number centres providing this treatment are also increasing making this curative treatment more widely available in India.
Increased Hepatic Iron Content Predicts Poor Survival in Patients With Iron Overload Who Underwent Allogeneic Hematopoietic Stem Cell Transplantation
2016, Clinical Lymphoma, Myeloma and Leukemia
Citation Excerpt :
Complications related to IO might increase transplant-related mortality in allogeneic stem cell transplant patients.14 These complications are post-transplant liver dysfunction,15 mucositis,16 bacterial, fungal, and viral infections,17-19 acute graft versus host disease (GVHD),20,21 and sinusoidal obstruction syndrome (SOS).7,22 IO might also present an exacerbation of hepatic GVHD after alloHSCT,23 so a liver biopsy might be useful for differential diagnosis in these circumstances.
Iron overload results in increased infection, venous-oclusive disease and hepatic dysfunction in allogeneic hematopoietic stem cell transplant (alloHSCT) recipients. Liver is one of the most common sites of iron overload.
A total of 50 alloHSCT recipients that underwent liver biopsy in Erciyes Stem Cell Transplantation Hospital, Erciyes University, between 2004 and 2011 were enrolled in the study. The liver biopsy specimens have been obtained from the archives of Erciyes University, Department of Pathology and stainned for iron content.
The mean age was found 34 ± 11 years. For median overall survival (OS); 53 months (min-max: 41-65) in patients with grade 0, 55 months (min-max: 47-64) in patients with grade 1, in patients with grade 2 patients 25.4 months (11.5-39.4 ), grade 3 patients 29.3 months (min-max: 12.3-46.3) and grade 4 patients 2.6 months (min-max: 2.0-3.3). Overall survival was correlated with the degree of liver iron content and it was statistically significant in Kaplan-Meier analysis (P < .001). Disease-free survival was found (DFS); grade 0 patients 47.1 months (min-max: 32.0-62.0), grade 1 patients 36.9 months (min-max: 21.0-65.0), grade 2 patients 23.5 months (min-max: 12.0-59.0), grade 3 patients 27.4 months (min-max: 5.3-59.3) and grade 4 patients 2.6 months (min-max: 2.0-3.0). For DFS; it was negatively correlated with the degree of liver iron content nevertheless; it was not was statistically significant in Kaplan-Meier analysis (P = .093).Hepatic iron overload might be associated with poor survival in patients with transfusional iron overload that underwent alloHSCT.
Hepatic iron content might be associated with poorer prognosis in patients with iron overload that underwent alloHSCT.
Allogeneic stem cell transplantation for thalassemia major
2014, Hematology/Oncology Clinics of North America
Citation Excerpt :
Use of a busulfan-based conditioning regimen was associated with an increased incidence of SOS on a multivariate analysis in a prospective study.23 The link between pretransplant iron overload and SOS is similarly well recognized.24 Although targeted busulfan levels and prophylaxis with defibrotide have significantly reduced this complication in patients with thalassemia major,16,18 it is still a significant complication among class III HR patients.
Transplantation pathology
2012, MacSween's Pathology of the Liver

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ReviewThe role of iron in patients after bone marrow transplantation

Summary

Free Radic Biol Med

Free Radic Biol Med

Free Radic Biol Med

Biochim Biophys Acta

Blood

Biol Blood Marrow Transplant

Blood

Blood Rev

Blood

Transplant Proc

Leuk Res

Blood

Nontransferrin-bound iron during allogeneic stem cell transplantation

Br J Haematol

Autografting as a risk factor for persisting iron overload in long-term survivors of acute myeloid leukaemia

Bone Marrow Transplant

Bone marrow transplantation in adults with thalassemia. Treatment and long-term follow-up

Ann NY Acad Sci

Prognostic factors and life expectancy in myelodysplastic syndromes classified according to WHO criteria: a basis for clinical decision making

J Clin Oncol

Non-transferrin-bound iron, iron-related oxidative stress and lipid peroxidation in beta-thalassemia intermedia

Transfus Sci

Nontransferrin-bound iron in myelodysplastic syndromes: a marker of ineffective erythropoiesis?

Hematol J

High levels of GDF15 in thalassemia suppress expression of the iron regulatory protein hepcidin

Nat Med

Rust and corrosion in hematopoietic stem cell transplantation: the problem of iron and oxidative stress

Bone Marrow Transplant

Decreased essential antioxidants and increased lipid hydroperoxides following high-dose radiochemotherapy

Free Radic Biol Med

Deteriorating free radical-trapping capacity and antioxidant status in plasma during bone marrow transplantation

Bone Marrow Transplant

Lipoperoxides as an index of free radical activity in bone marrow transplant recipients. Preliminary observations

Biol Trace Elem Res

Iron overload is a major risk factor for severe infection after autologous stem cell transplantation: a study of 367 myeloma patients

Bone Marrow Transplant

Early clinical impact of iron overload in stem cell transplantation. A prospective study

Ann Hematol

Frequent severe liver iron overload after stem cell transplantation and its possible association with invasive aspergillosis

Bone Marrow Transplant

Review
The role of iron in patients after bone marrow transplantation