Transfusional iron overload in patients receiving autologous stem cell transplantation: An underestimated problem requiring further consideration
Transfusion and apheresis science : official journal of the World Apheresis Association : official journal of the European Society for Haemapheresis. 2020;:102837
Retrospective Evaluation of Relationship Between Iron Overload and Transplantation Complications in Pediatric Patient Who Underwent Allogeneic Stem Cell Transplantation Due to Acute Leukemia and Myelodysplastic Syndrome
Journal of pediatric hematology/oncology. 2020
BACKGROUND Hematopoietic stem cell transplantation (HSCT) is a curative therapy option for hematologic malignancies. Iron overload is common in this patient group and can impact short-term and long-term nonrelapse mortality. STUDY DESIGN Retrospective observational cohort study. AIMS To evaluate the effect of iron load on early and late HSCT outcomes in patients with acute leukemia and myelodysplasia in order to assess the necessity of reducing iron load. PATIENTS AND METHODS Sixty patients who underwent HSCT in pediatric stem cell transplantation unit between 2000 and 2012 were evaluated retrospectively. The patients were divided into those with pretransplantation serum ferritin levels above and below the median value of 1299 ng/mL. RESULTS Forty-two (70%) of the patients were male, mean ages of the low and high ferritin groups were 85.43+/-9.42 and 118.56+/-10.04 months, respectively. Acute graft-versus-host disease (GVHD) within the first 100 days and acute liver GVHD were significantly more common in the high ferritin group (P<0.011 for both). Ferritin level was not associated with rates of engraftment syndrome, veno-occlusive disease, early/late infection, relapse, or overall and disease-free survival. CONCLUSIONS In our study, significant result especially in terms of acute liver GVHD, was important to emphasize the need to be more careful in terms of acute liver GVHD risk in early liver pathologies in patients with high levels of ferritin after transplantation. In future large studies may be helpful to explain the relationship between acute liver GVHD and high ferritin levels.
Iron Overload is Associated with Delayed Engraftment and Increased Non-Relapse Mortality in Recipients of Umbilical Cord Blood Hematopoietic Cell Transplantation
Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation. 2020
The negative impact of Iron overload (IO) on outcomes of allogeneic hematopoietic cell transplantation (HCT) is well-recognized, but its impact on umbilical cord blood (UCB) transplant outcome is unknown. We retrospectively analyzed outcomes of 150 patients who received UCB-HCT at our institution, stratified by pre-HCT serum ferritin level (SF) of 2000 ng/ml. Two-year overall survival rate among patients with SF >2000 and ≤2000 ng/ml was 26.1% (95%CI: 10.6%-44.7%) and 52.1% (95%CI: 40.1%-62.8%), respectively; HR=2.26 (95%CI: 1.28-4.00, P=0.005). Two-year non-relapse mortality rate was higher among patients with SF >2000 ng/ml (56.5%, 95%CI: 33.3%-74.4%) compared to SF ≤2000 ng/ml (30.1%, 95%CI: 20.0%-40.9%); HR=2.18, (95%CI: 1.10-4.31, P=0.025). Neutrophil engraftment at 42 days was 78.3% (95%CI: 53.5%-90.8%) in patients with SF >2000 ng/ml, versus 91.8% (95%CI: 82.1%-96.4%) in patients with SF ≤2000 ng/ml; HR=0.58 (95%CI: 0.35-0.96, P=0.034). A significant difference in platelet engraftment at 3 months was also observed: 52.2% (95%CI: 29.4%-70.8%) for SF>2000 ng/ml versus 80.8% (95%CI: 69.5%-88.3%) for SF ≤2000 ng/ml; HR=0.48 (95%CI: 0.23-0.98, P=0.044). In conclusion, IO defined by SF of 2000 ng/ml is a strong adverse prognostic factor for UCB-HCT and should be a considered when UCB is chosen as the graft source for patients without a fully matched donor.
Evaluation of liver tissue by ultrasound elastography and clinical parameters in children with multiple blood cell transfusions
Pediatric radiology. 2019
BACKGROUND Children receiving multiple blood cell transfusions are prone to iron overload and successive tissue damage in liver parenchyma, making noninvasive screening options desirable. Ultrasound (US) elastography using acoustic radiation force impulse (ARFI) imaging enables evaluation of liver parenchyma stiffness, and MRI allows for quantification of liver iron concentration. OBJECTIVE The objective was to correlate US elastography with MRI in children who had undergone bone marrow transplantation and to evaluate the modification of liver tissue with US in combination with clinical parameters at follow-up. MATERIALS AND METHODS ARFI, T2*-weighted MRI and a clinical score (HepScore, based on parameters of liver function) were performed in 45 patients (24 male; mean age 9.7 years) before and 100 days and 365 days after transplantation. All received multiple blood transfusions (mean number 22.2 up until 1 year after transplantation). We correlated US findings and HepScore with MRI findings. RESULTS We observed signs of iron accumulation in 29/45 (64.4%) patients on MRI (T2*<10 ms) and 15/45 (33.3%) showed increased tissue stiffness (ARFI>5.5 kPa). Correlation of elastography and MRI was not significant (P=0.57; n=51 matched measurements). Comparing US elastography with HepScore in receiver operating characteristic (ROC) curve analysis indicated a cut-off for affected parenchyma if HepScore was >5 points (sensitivity 67%, specificity 68%). Simultaneous increases of both indicated tissue alteration. CONCLUSION Combining US and HepScore enabled detection of liver tissue alteration through iron overload, but we found no direct significant effect of estimated iron from MRI on ARFI imaging.
MRI as an alternative to serum ferritin for diagnosis of iron overload in children in the context of immune response after stem cell transplantation
Pediatric transplantation. 2019;:e13583
Multiple blood cell transfusions may cause iron overload or even liver fibrosis, requiring early diagnosis and intervention. SF is the standard for estimating iron levels in the body, but it also increases with inflammation. We hypothesized that T2 * magnetic resonance (MR) relaxometry is a more accurate alternative for follow-up in pediatric patients before and after allogenic SCT. Twenty-three children (mean age 10.2 years, 10 female, 13 male) were evaluated prospectively before SCT as well as at least 1 year after SCT with T2 * relaxometry on a 1.5 T MR-scanner to estimate liver iron concentrations from the T2 * values ("MR-Fe"). The results were compared with SF, while also considering CRP, and correlated with the number of transfusions. Overall, 24.3 transfusions were administered in average, mainly within 100 days of SCT (mean 10.5 units). Both MR-Fe and SF increased after SCT and decreased in the absence of new transfusions 1 year later without chelate therapy. This suggests regeneration of LP and iron loss, although the original states were not reached. Additionally, simultaneous peaks of CRP and SF were observed directly after SCT. MR-Fe did neither reveal these peaks nor was it associated with CRP (P = .39). We postulate that these early CRP and SF peaks after SCT are probably related to inflammatory reactions and not to iron overload. Thus, SF is not reliable for iron overload diagnosis after SCT in every condition. Beside this interaction, SF and MR-Fe revealed similar accuracy. MRI, however, has practical and economical disadvantages in routine estimation of iron.
Hepatic focal nodular hyperplasia after pediatric hematopoietic stem cell transplantation: The impact of hormonal replacement therapy and iron overload
Pediatric blood & cancer. 2019;:e28137
BACKGROUND The advent of techniques for the assessment of iron overload (liver T2*-MRI) has led to the awareness that focal nodular hyperplasia (FNH) represents a possible incidental finding after hematopoietic stem cell transplantation (HSCT), though its pathogenesis is still unclear. METHODS We performed a retrospective analysis of the liver T2*-MRI scans performed between 2013 and 2018 in a single pediatric HSCT Unit and recorded the number of patients with FNH (group A). Patients incidentally diagnosed with FNH at imaging performed for different clinical indications were included in group B. RESULTS Nine of 105 (8.6%) patients from group A were diagnosed with FNH. Group B included three patients. Overall, 12 patients were diagnosed 4.4 +/- 3.1 years after HSCT. At univariate analysis, female gender (odds ratio [OR] 3.77, P = .03), moderate-to-severe iron overload (OR 6.97, P = .01), and hormone replacement therapy (HRT) administered for at least 6 months (OR 18.20, P = .0002) exposed patients to a higher risk of developing FNH. The detrimental effect of HRT was significant also at multivariate analysis (OR 7.93, P = .024). MRI-T2* values in affected patients were statistically lower than healthy controls (P < .001). CONCLUSIONS We confirm the high incidence of FNH among transplanted pediatric patients and demonstrate the potential pathogenic role of HRT and iron overload.
Efficacy and safety of oral deferasirox treatment for transfusional iron overload in pure red cell aplasia patients after allogeneic stem cell transplantation
Annals of hematology. 2019
Improved survival outcomes and restoration of graft-vs-leukemia effect by deferasirox after allogeneic stem cell transplantation in acute myeloid leukemia
Cancer medicine. 2019
Deferasirox is an oral iron-chelating agent having possible antileukemia and immune modulatory effects. Few reports have evaluated deferasirox in the setting of allogeneic hematopoietic stem cell transplantation (allo-HSCT). We investigated the impact of deferasirox after allo-HSCT in acute myeloid leukemia (AML). Of 326 consecutive patients undergoing allo-HSCT in remission, analysis of 198 patients not receiving deferasirox revealed the negative prognostic effect of hyperferritinemia (≥1000 ng/mL) before and after allo-HSCT on survival mainly due to increase in relapse. Of 276 patients with hyperferritinemia at 1 month after allo-HSCT, 128 patients (46%) received deferasirox. Deferasirox induced a faster decline in serum ferritin level with a manageable safety profile, which significantly reduced relapse rather than nonrelapse mortality, resulting in better survival compared to patients not receiving deferasirox. Of note, the deferasirox group had a significantly higher incidence of chronic graft-vs-host disease, indicating improved graft-vs-leukemia (GVL) effects evidenced by the presence of suppressed regulatory T cells and sustained higher proportion of NK cells in peripheral blood. This study firstly demonstrates the improved survival and restoration of GVL effects of patients with AML by deferasirox, which also clarifies the detrimental effect of hyperferritinemia through after allo-HSCT.
Serum ferritin is not a reliable predictor to determine iron overload in thalassemia major patients post hematopoietic stem cell transplantation
European journal of haematology. 2018
OBJECTIVE Iron overload (IO) in transfusion-dependent anemia persists after hematopoietic stem cell transplantation (HSCT) and can cause long-term organ damage. In many studies, the diagnosis of IO before and after HSCT is based on serum ferritin (SF) levels rather than on assessment of liver iron concentration (LIC) by MRI or SQUID. METHOD In a multicenter, retrospective study we analyzed the concordance for indication of iron depletion therapy and correlation between LIC and SF of 36 thalassemia patients after HSCT. LIC was determined either by MRI-R2 (Ferriscan((R)) ) or SQUID. RESULTS The concordance between LIC and SF varies over time after transplant (P=0.011). The correlation between SF and LIC was strong in the first year (Spearman's rho 0.75; P<0.001). In agreement, the concordance between SF and LIC concerning indication for treatment was close to 1 with an overall error rate ca. of 10%. Especially in the first year after HSCT, SF underestimates the degree of iron overload. However, in the longitudinal analysis since the second year post HSCT onwards no association was found between LIC and SF (P=0.217). Furthermore, in the second year after HSCT the overall error rate was 35% whereas in the 3(rd) , 4(th) and >4(th) year it was 58%, 60% and 25%, respectively. CONCLUSIONS Our data suggest serum ferritin is not a reliable predictor to determine iron overload in thalassemia patients after HSCT. This article is protected by copyright. All rights reserved.
One-year results from a prospective randomized trial comparing phlebotomy with deferasirox for the treatment of iron overload in pediatric patients with thalassemia major following curative stem cell transplantation
Pediatric Blood & Cancer. 2017;64(1):188-196
BACKGROUND Iron overload is well documented in patients with beta-thalassemia major, and patients who have undergone hematopoietic stem cell transplantation (HSCT) remain at risk as a result of pre- and immediate post-HSCT transfusions. PROCEDURE This is a prospective, randomized, 1-year clinical trial that compares the efficacy and safety of the once-daily oral iron chelator deferasirox versus phlebotomy for the treatment of iron overload in children with beta-thalassemia major following HSCT. RESULTS Patients (aged 12.4 years) received deferasirox (n = 12, 10 mg/kg/day starting dose) or phlebotomy (n = 14, 6 ml/kg/2 weeks) for 1 year. In two and five patients, deferasirox dose was increased to 15 and 20 mg/kg/day, respectively. Magnetic resonance imaging (MRI)-assessed liver iron concentration (LIC) decreased with deferasirox (mean 12.5 +/- 10.1 to 8.5 +/- 9.3 mg Fe/g dry weight [dw]; P = 0.0005 vs. baseline) and phlebotomy (10.2 +/- 6.8 to 8.3 +/- 9.2 mg Fe/g dw; P = 0.05). LIC reductions were greater with deferasirox than with phlebotomy for patients with baseline serum ferritin 1,000 ng/ml or higher (-8.1 +/- 1.5 vs. -3.5 +/- 5.7 mg Fe/g dw; P = 0.048). Serum ferritin and non-transferrin-bound iron also decreased significantly. In two patients with severe cardiac siderosis, a clinically relevant improvement in myocardial T2* was seen, following phlebotomy and deferasirox therapy (n = 1 each). Adverse effects with deferasirox were skin rash, gastrointestinal upset, and increased liver function tests (all n = 1), while those for phlebotomy were difficulty with venous access (n = 4) and distress during procedure (n = 1). Parents of 13/14 children receiving phlebotomy wished to switch to deferasirox, with 1/14 being satisfied with phlebotomy. CONCLUSIONS Deferasirox treatment or phlebotomy reduces iron burden in pediatric patients with beta- thalassemia major post-HSCT, with a manageable safety profile. Copyright © 2016 Wiley Periodicals, Inc.