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

Abstract

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...

Unrelated cord blood transplantation in adults with myelodysplasia or secondary acute myeloblastic leukemia: a survey on behalf of Eurocord and CLWP of EBMT

“…Disease duration before transplantation or iron overload has been regularly found to increase NRM and sometimes decrease survival in bone marrow or peripheral blood transplant recipients. [33][34][35][36] Our study confirmed that RIC before UCBT is associated with a reduction in NRM, as observed in unrelated HSCT recipients. 36 Despite poorer general conditions and high-risk MDS, patients who received RIC had decreased NRM and a trend toward better DFS.…”

Effect of iron overload and iron-chelating therapy on allogeneic hematopoietic SCT in children

“…These results were in concert with earlier studies that reported the clinical relevance of iron overload with TRM and survival. 7,8 A recent study reported a strong association of elevated serum ferritin level with lower OS and diseasefree survival in HSCT patients, and this association was restricted to patients with acute leukemia or myelodysplastic syndrome. 8 We did subgroup analysis with the patients other than acute leukemia or myelodysplastic syndrome and found that TRM of the F41000 group (50%) was higher than those of Fo1000 group (6.7%) and IC group (0%), but this was not statistically significant (P ¼ 0.060).…”

“…Free iron catalyzes the conversion of reactive oxygen species intermediates to highly toxic-free radicals, which may mediate tissue injury. 2 Recent studies have shown that iron overload is related to hepatic complications, 3 infectious complications [4][5][6] and survival 7,8 in HSCT.…”

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

“…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.…”