Iron depletion by phlebotomy with recombinant erythropoietin prior to allogeneic transplantation to prevent liver toxicity

Serna, Javier de la; Bornstein, Rafael; García-Bueno, María José; Lahuerta-Palacios, Juan J.

doi:10.1038/sj.bmt.1701534

Cited by 11 publications

(7 citation statements)

References 7 publications

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“…The cumulative incidence rate of invasive aspergillosis (about 14%) after myeloablative and nonmyeloablative conditioning has increased in recent years 34 and is one of the main causes of death in transplanted patients. If these results are reproduced with prospective data, pre-transplant manoeuvres to decrease iron overload 35 or transferrin saturation with human transferrin infusions during conditioning 36 would be proposed to lower TRM and improve survival.…”

Section: Discussionmentioning

confidence: 92%

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

120

106

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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: 92%

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

120

106

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“…13 Further studies to confirm our findings are mandatory. If these results are reproduced, pre-transplant strategies to decrease iron overload 14 could be proposed to decrease TRM and improve survival.…”

Section: Discussionmentioning

confidence: 99%

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

Altés

Remacha

Sureda

et al. 2002

Bone Marrow Transplant

117

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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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“…The use of recombinant human erythropoietin may facilitate this strategy in patients who have low hemoglobin levels. 81,82 Late complications of bones and joints…”

Section: Iron Overloadmentioning

confidence: 99%

Nonmalignant late effects after allogeneic stem cell transplantation

Socié

Salooja²,

Cohen³

et al. 2003

Blood

376

208

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Iron depletion by phlebotomy with recombinant erythropoietin prior to allogeneic transplantation to prevent liver toxicity

Cited by 11 publications

References 7 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

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

Nonmalignant late effects after allogeneic stem cell transplantation

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