Myocardial iron overload in transfusion‐dependent pediatric patients with acute leukemia

Lutz, Kira; Komorowski, G. von; Dürken, Matthias; Engelhardt, R.; Dinter, Dietmar

doi:10.1002/pbc.21663

Cited by 21 publications

(16 citation statements)

References 11 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Although the absence of measurable cardiac iron is a pertinent negative finding that seems reassuring, caution is warranted as isolated case reports of cardiac iron loading have been published (10,28) and the problem may have been under-represented in our cohort. Furthermore, much remains unknown about the fate of transfusion-derived iron during pediatric cancer treatment.…”

Section: Discussionmentioning

confidence: 82%

“…Furthermore, much remains unknown about the fate of transfusion-derived iron during pediatric cancer treatment. Research is needed to elucidate how normal iron homeostasis might be modified in this population through suppression of erythropoiesis by chemotherapy, the inflammatory effects of infections and tissue breakdown, altered nutrition, and circulating factors emanating from the neoplasms themselves that could affect organ function (10,28).…”

Section: Discussionmentioning

confidence: 99%

“…Transfusional IO has been well documented among children with nononcologic conditions such as chronic hemolytic anemia (3). Although preliminary evidence for transfusional IO in pediatric oncology patients has been documented (4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18), its prevalence, organ distribution, and severity remain incompletely characterized. Historically, direct measurement of tissue iron has been limited almost exclusively to liver biopsy.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Characterization of Transfusion-Derived Iron Deposition in Childhood Cancer Survivors

Ruccione

Wood

Sposto

et al. 2014

Cancer Epidemiology, Biomarkers &Amp; Prevention

View full text Add to dashboard Cite

Background: Childhood cancer survivors (CCS) receiving packed red blood cell (PRBC) transfusions may have increased risk for vital organ iron deposition causing serious late effects.Methods: This cross-sectional cohort study of a CCS cohort quantified organ iron content by magnetic resonance imaging. Iron status by serum markers and hemochromatosis gene mutation status were assessed.Results: Seventy-five patients who had received a range (0-392 mL/kg) of cumulative PRBC transfusion volumes were enrolled (median age 14 years, range 8-25.6 years at evaluation). Median follow-up time was 4.4 years, and median time since last transfusion was 4.9 years. Cancer diagnoses included acute lymphoblastic or myelogenous leukemia (ALL/AML; n ¼ 33) and solid tumors (n ¼ 42). Liver and pancreatic iron concentrations were elevated in 36 of 73 (49.3%) and 19 of 72 (26.4%) subjects, respectively. Cardiac iron concentration was not increased in this cohort. In multivariate analysis, cumulative PRBC volume (P < 0.0001) and older age at diagnosis (P < 0.0001) predicted elevated liver iron concentration.Conclusions: Iron overload (IO) may occur in children and adolescents/young adults treated for cancer and is associated with cumulative PRBC transfusion volume and age at diagnosis.Impact: These findings have implications for development of monitoring and management guidelines for cancer patients and survivors at risk for IO, exploration of the additive risk of liver/pancreatic damage from chemotherapeutic exposures, and health education to minimize further liver/pancreatic damage from exposures such as excessive alcohol intake and hepatotoxic medications. Cancer Epidemiol Biomarkers Prev; 23(9); 1913-9. Ó2014 AACR.

show abstract

Section: Discussionmentioning

confidence: 82%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Characterization of Transfusion-Derived Iron Deposition in Childhood Cancer Survivors

Ruccione

Wood

Sposto

et al. 2014

Cancer Epidemiology, Biomarkers &Amp; Prevention

View full text Add to dashboard Cite

show abstract

“…However, those patients were exposed to blood transfusions over 5 to 6 years and subsequently underwent regular phlebotomy because their iron overload was diagnosed after the completion of chemotherapy. 16 Although the cardiac iron levels in their patients and ours are not usually associated with cardiac dysfunction, they do indicate substantial exposure to toxic free iron. The identification of accelerated iron overload should prompt evaluation for underlying etiology.…”

Section: Discussionmentioning

confidence: 57%

“…Our patient's cardiac T2* of 15.6 milliseconds indicated moderate cardiac iron load. 15 Lutz et al 16 reported 2 other children with ALL who developed cardiac iron overload, where the cardiac T2* values were 19 and 20 milliseconds, respectively. However, those patients were exposed to blood transfusions over 5 to 6 years and subsequently underwent regular phlebotomy because their iron overload was diagnosed after the completion of chemotherapy.…”

Section: Discussionmentioning

confidence: 99%

Early Cardiac Iron Overload in a Child on Treatment of Acute Lymphoblastic Leukemia

2015

View full text Add to dashboard Cite

An 11-year-old boy with Down syndrome and acute lymphoblastic leukemia developed hepatic dysfunction after only 10 months of treatment. MRI revealed severe iron deposition in the liver, pancreas, and heart. In stark contrast to what is seen in hemoglobinopathies, pancreatic and cardiac iron overload occurred with relatively low transfusion exposure and in a very short time period in this patient. Although extensive experience managing iron overload in hemoglobinopathies informs our approach in other diseases, it is clear that factors not present in hemoglobinopathies may be operative in patients with malignancy undergoing intense chemotherapy that lead to high levels of free iron and rapid loading of the heart and endocrine organs.

show abstract

Impact of hemochromatosis gene mutations on cardiac status in doxorubicin‐treated survivors of childhood high‐risk leukemia

Lipshultz

Lipsitz

Kutok

et al. 2013

Cancer

141

View full text Add to dashboard Cite

Background Doxorubicin is associated with progressive cardiac dysfunction, possibly by forming doxorubicin-iron complexes leading to free-radical injury. We determined the frequency of hemochromatosis (HFE) gene mutations associated with hereditary hemochromatosis and their relationship with doxorubicin-associated cardiotoxicity in survivors of childhood high-risk acute lymphoblastic leukemia. Methods Peripheral blood was tested for two common HFE allelic variants: C282Y and H63D. Serum cardiac troponin-T (cTnT) and N-terminal pro-brain natriuretic peptide (NT-proBNP), biomarkers of cardiac injury and cardiomyopathy, respectively, were assayed during therapy. Left ventricular (LV) structure and function were assessed with echocardiography. Results 184 patients had DNA results for at least one variant, and 167 had both: 24% carried H63D and 10% carried C282Y. Heterozygous C282Y genotype was associated with multiple elevations in cTnT concentrations (p=0.039), but not NT-proBNP. At a median of 2.2 years (1.0–3.6) after diagnosis, mean [SE] Z-scores for LV fractional shortening (−0.71 [0.25], p=0.008), mass (−0.84 [0.17], p<0.001), and end-systolic (−4.36 [0.26], p<0.001) and end-diastolic posterior wall thickness (−0.68 [0.25], p=0.01) were abnormal in children with either allele (n=32). Non-carriers (n=63) also had below-normal LV mass (−0.45 [0.15], p=0.006) and end-systolic posterior wall thickness (−4.06 [0.17], p<0.001). Later follow-up showed similar results. Conclusions Doxorubicin-associated myocardial injury was associated with C282Y HFE carriers. Although LV mass and wall thickness were abnormally low overall, they were even lower in HFE carriers, who also had reduced LV function. Screening newly-diagnosed cancer patients for HFE mutations may identify those at risk for doxorubicin-induced cardiotoxicity.

show abstract

Myocardial iron overload in transfusion‐dependent pediatric patients with acute leukemia

Cited by 21 publications

References 11 publications

Characterization of Transfusion-Derived Iron Deposition in Childhood Cancer Survivors

Characterization of Transfusion-Derived Iron Deposition in Childhood Cancer Survivors

Early Cardiac Iron Overload in a Child on Treatment of Acute Lymphoblastic Leukemia

Impact of hemochromatosis gene mutations on cardiac status in doxorubicin‐treated survivors of childhood high‐risk leukemia

Contact Info

Product

Resources

About