Iron metabolism and fungal infections in patients with haematological malignancies.

Iglesias-Osma, María Carmen; González-Villaron, Luis; Miguel, Jesús F. San; Caballero, M D; Vázquez, Lourdes; Castro, Sonia de

doi:10.1136/jcp.48.3.223

Cited by 53 publications

(44 citation statements)

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“…26 Interestingly, previous clinical papers have related iron overload and infection in immuno-deficient patients, and the infection was always produced by Aspergillus or Mucor. [27][28][29] In our series, Aspergillus infection was not related with neutropenia or acute GVHD, probably because 41% of cases were autologous transplants and the number of patients with long-standing neutropenia or severe acute GVHD was low. An association between CMV disease and fungal infections has been noted not only in solid organ transplant recipients 30,31 but also in recipients of HSCT.…”

Section: Discussionmentioning

confidence: 85%

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

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Remacha

Sarda

et al. 2004

Bone Marrow Transplant

119

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Summary:Iron overload is associated with free radical generation and tissue damage. Our main objective was to ascertain the frequency and severity of iron overload in a group of 59 patients who died after conventional-intensity autologous (n ¼ 24) or allogeneic (n ¼ 35) haematopoietic stem cell transplantation (HSCT). A second objective was to investigate associations between liver-iron concentration and causes of transplant-related mortality. The median age was 41 years (range, 19-66), 41 were males and 18 females. In total, 26 patients had acute leukaemia or MDS, 10 CML, 17 lymphoma, four myeloma and two aplastic anaemia. The median hepatic iron concentration (HIC) was 138 lmol/g dry weight (7.7 mg/g; range 31-631 lmol/g). In total, 4/32 (12%) patients with HIC o150 lmol/g and 10/27 (37%) with hepatic iron X150 lmol/g showed invasive aspergillosis at autopsy (P ¼ 0.035). This was significant in multivariate analysis (RR 9.0; 95% CI 1.6-50.3, P ¼ 0.012). In conclusion, severe iron overload is frequent in patients who die following HSCT and is associated with invasive aspergillosis.

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Section: Discussionmentioning

confidence: 85%

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

Altés

Remacha

Sarda

et al. 2004

Bone Marrow Transplant

119

106

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“…Iron overload has been associated with increased susceptibility to organ damage and increased risk of infection [14,15]. Patients undergoing HSCT often have received multiple blood transfusions prior to transplantation, which probably contribute to elevated ferritin levels.…”

Section: Discussionmentioning

confidence: 99%

Pretransplant serum ferritin level may be a predictive marker for outcomes in patients having undergone allogeneic hematopoietic stem cell transplantation

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Baldane²,

Kaynar³

et al. 2012

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Iron overload increases the risk of infections, veno-occlusive disease and hepatic dysfunction in post-transplant period. Our objective was to investigate the association of pre-transplant ferritin levels with complications and survival after allogeneic hematopoietic stem cell transplantation (alloHSCT).We retrospectively analysed 84 patients' data who had undergone allogeneic HSCT into two groups: patients with a serum ferritin level≥1000ng/ml, and patients with <1000 ng/ml at the time of HSCT.Cox-regression analysis showed that pre-transplant serum ferritin levels were significantly higher in patients who had at least one infectious event compared with those who had no any infectious event in the post-transplant 100 days (p<0.023). Overall survival (OS) and disease-free survival (DFS) rates were significantly higher in patients with a time-to-tx interval <12 months compared with group time-to-tx interval>12 months (p=0.002 and p=0.008 respectively). A higher risk of death was observed in high-ferritin group (hazard ratio=2.27, CI:1.01-5.09, p=0.023 for OS and hazard ratio=2.49, CI:1.12-5.53 p=0.039 for DFS). No significant effect on OS and DFS among groups was observed for variables conditioning regimen, gender and diagnosis. Acute GVHD was more common in patients with a ferritin level ≥1000 ng /mL, but this was not statistically significant (p>0.05). There was no statistical significance in both groups (ferritin≥1000ng /mL and ferritin<1000ng/mL) for relapse rates (p>0.05). Platelet and neutrophil engaftment day was not found statistically significant compared with both groups (p=0.273 and p=0.882, respectively).Pre-transplant ferritin levels may predict poor outcomes in patients who had undergone allogeneic hematopoietic stem cell transplantation.

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“…9 Hyperferraemia can predispose to bacterial and fungal infections. 10 Increased TS and ferritin are proven risk factors for the development of systemic fungal infections in patients with haematological malignancies, 11 and, accordingly, patients submitted to liver transplant caused by haemo-chromatosis are at a greater risk of dying from fungal infections than patients without iron overload submitted to the same transplant type. 12 An increase in some late fungal infections, specially mucormycosis, have been reported in iron loaded patients after HSCT.…”

Section: Discussionmentioning

confidence: 99%

Iron overload might increase transplant-related mortality in haematopoietic stem cell transplantation

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Remacha

Sureda

et al. 2002

Bone Marrow Transplant

116

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Summary:Iron overload (IO) is associated with free radical generation and tissue damage. Our main objective was to ascertain if very high levels (VHL) of ferritin (у3000 g/l) and transferrin saturation (TS) у100% during conditioning had an impact on overall survival (OS) and transplant-related mortality (TRM) after a haematopoietic stem cell transplantation (HSCT). Levels of ferritin and TS were measured at days ؊7 and ؊4, respectively, in 25 patients who underwent HSCT after CY/TBI. The group consisted of 20 men and five women with a median age of 40 years. Fifteen patients were autotransplanted and 10 allotransplanted. Nine of them had a diagnosis of AL, six of CML and 10 of lymphoma. Thirteen of them were in early and 12 in advanced status of disease. VHL of ferritin and TS у100% were associated with a decreased OS (P ‫؍‬ 0.001 and P ‫؍‬ 0.006, respectively) and an increased TRM (P ‫؍‬ 0.003 and P ‫؍‬ 0.004, respectively) in univariate survival analysis. Both variables remained significant at multivariate analysis for OS (P ‫؍‬ 0.03 and 0.02, respectively) and TS was an independent factor for TRM (P ‫؍‬ 0.01). Ferritin was very close to achieving statistical significance for TRM (P ‫؍‬ 0.06) in multivariate analysis. In conclusion, VHL of ferritin and TS у100% at conditioning are associated with an increase in toxic deaths after transplant. Bone Marrow Transplantation (2002) 29, 987-989. DOI: 10.1038/sj/bmt/1703570 Keywords: iron; transferrin saturation; ferritin; survival; TRM; HSCT Iron overload (IO) is associated with free radical production and tissue damage in different diseases such as genetic haemochromatosis and secondary IO. 1,2 IO may be present among patients who undergo haematopoietic stem cell transplantation (HSCT) due to prior blood transfusions. Pre-transplant iron status may be evaluated measuring ferritin levels pre-conditioning; that is a time when ferritin is still neither increased as an acute phase reactant nor influenced by liver toxicity secondary to chemo-radiotherapy. Moreover, transferrin saturation (TS) increases during chemo-radiotherapy, often reaching indexes of over 80% and producing non-transferrin-bound iron (NTBI). 3,4 TS might inform us about the potentially toxic effect of free iron, without any protein control, produced during conditioning. It is likely that an IO status pre-conditioning with an elevated TS during this procedure for HSCT may increase the toxic effects of chemo-radiotherapy. 5 This could cause an increase in transplant-related mortality (TRM) and a subsequent decrease in overall survival (OS). The aim of this study was to determine whether a very high level of ferritin pre-conditioning and/or a full TS during CY-TBI were independent risk factors for TRM and OS. Patients and methodsTwenty-five consecutive patients who underwent HSCT with CY/TBI were prospectively enrolled in the study. All patients were conditioned with cyclophosphamide 60 mg/kg once daily i.v. on days Ϫ6 and Ϫ5 (total dose 120 mg/kg) and TBI 6 ϫ 2 Gy from days Ϫ3 to Ϫ1. GVHD prophylaxis in...

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Iron metabolism and fungal infections in patients with haematological malignancies.

Abstract: (T Clin Pathol 1995;48:223-225)

Cited by 53 publications

References 20 publications

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

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

Pretransplant serum ferritin level may be a predictive marker for outcomes in patients having undergone allogeneic hematopoietic stem cell transplantation

Iron overload might increase transplant-related mortality in haematopoietic stem cell transplantation

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Iron metabolism and fungal infections in patients with haematological malignancies.

Abstract: (T Clin Pathol 1995;48:223-225)

Cited by 53 publications

References 20 publications

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

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

Pretransplant serum ferritin level may be a predictive marker for outcomes in patients having undergone allogeneic hematopoietic stem cell transplantation

Iron overload might increase transplant-related mortality in haematopoietic stem cell transplantation

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Pretransplant serum ferritin level may be a predictive marker for outcomes in patients having undergone allogeneic hematopoietic stem cell transplantation