Iron Overload in Children Who Are Treated for Acute Lymphoblastic Leukemia Estimated by Liver Siderosis and Serum Iron Parameters

Halonen, Päivi; Mattila, Jouni; Suominen, Pauli; Ruuska, Tarja; Salo, Matti K.; Mäkipernaa, Anne

doi:10.1542/peds.111.1.91

Cited by 58 publications

(47 citation statements)

References 35 publications

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“…It has been speculated that because CCSs usually terminate their transfusions upon completion of cancer treatment, they might substantially draw down their iron load over time through continued growth and development (7,18). Given there is no mechanism for active excretion of excess iron, our results suggest that older children and adolescents exposed to multiple transfusions during cancer therapy may be less able to expend iron stores and sustain lifelong exposure to toxic iron, which could result in organ dysfunction many years after cure of their malignancy.…”

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%

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Characterization of Transfusion-Derived Iron Deposition in Childhood Cancer Survivors

Ruccione

Wood

Sposto

et al. 2014

Cancer Epidemiology, Biomarkers &Amp; Prevention

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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.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Characterization of Transfusion-Derived Iron Deposition in Childhood Cancer Survivors

Ruccione

Wood

Sposto

et al. 2014

Cancer Epidemiology, Biomarkers &Amp; Prevention

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“…Intensified chemotherapeutic protocols for childhood leukemia have necessitated more frequent blood transfusions, which can predispose patients to iron overload (57). It may thus be detrimental to transfuse packed red blood cells into these patients, with little regard for the resulting iron overload that ensues.…”

Section: Discussionmentioning

confidence: 99%

HIV-1 Rev–binding protein accelerates cellular uptake of iron to drive Notch-induced T cell leukemogenesis in mice

Khwaja¹,

Liu²,

Tong³

et al. 2010

J. Clin. Invest.

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Somatic activating mutations in Notch1 contribute to the pathogenesis of T cell acute lymphoblastic lymphoma (T-ALL), but how activated Notch1 signaling exerts this oncogenic effect is not completely understood. Here we identify HIV-1 Rev-binding protein (Hrb), a component of the clathrin-mediated endocytosis machinery, as a critical mediator of Notch-induced T-ALL development in mice. Hrb was found to be a direct transcriptional target of Notch1, and Hrb loss reduced the incidence or delayed the onset of T-ALL in mouse models in which activated Notch1 signaling either contributes to or drives leukemogenesis. Consistent with this observation, Hrb supported survival and proliferation of hematopoietic and T cell precursor cells in vitro. We demonstrated that Hrb accelerated the uptake of transferrin, which was required for upregulation of the T cell protooncogene p21. Indeed, iron-deficient mice developed Notch1-induced T-ALL substantially more slowly than control mice, further supporting a critical role for iron uptake during leukemogenesis. Taken together, these results reveal that Hrb is a critical Notch target gene that mediates lymphoblast transformation and disease progression via its ability to satisfy the enhanced demands of transformed lymphoblasts for iron. Further, our data suggest that Hrb may be targeted to improve current treatment or design novel therapies for human T-ALL patients.

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“…The sum of these scores defines the total iron score (TIS; range: 0-60). According to Halonen et al [17] , liver TIS is classified into mild iron overload (TIS 0-14), moderate iron overload (TIS 15-29) and severe iron overload (TIS 30-60). Steatosis was graded based on percent of hepatocytes involved; mild (< 33%), moderate (33%-66%) and severe (> 66%) [18] .…”

Section: Histological Evaluationmentioning

confidence: 99%

Assessment of hepatic fibrosis in pediatric cases with hepatitis C virus in Egypt

El-Hawary

Esmat²,

Soliman³

et al. 2007

WJG

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Iron Overload in Children Who Are Treated for Acute Lymphoblastic Leukemia Estimated by Liver Siderosis and Serum Iron Parameters

Abstract: Long-term iron overload is detected in at least 14% of children after therapy for acute lymphoblastic leukemia. Serum sTfR is an inappropriate marker for liver iron overload, whereas ferritin seems to be the most useful serologic marker for it.

Cited by 58 publications

References 35 publications

Characterization of Transfusion-Derived Iron Deposition in Childhood Cancer Survivors

Characterization of Transfusion-Derived Iron Deposition in Childhood Cancer Survivors

HIV-1 Rev–binding protein accelerates cellular uptake of iron to drive Notch-induced T cell leukemogenesis in mice

Assessment of hepatic fibrosis in pediatric cases with hepatitis C virus in Egypt

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