Abstract
Background: Recent studies have shown that an elevated ferritin level prior to hematopoietic stem cell transplant (HSCT), serving as a surrogate marker of body iron load, is independently associated with transplant related mortality (TRM) and inferior overall survival (OS) in adult oncology patients. Study Design and Methods: We performed a retrospective cohort study of 112 children with leukemia treated at our institution over a 10 year period, and compared TRM and OS after HSCT in those children with and without high red-blood cell (RBC) transfusions. Both groups were similar in regards to age, diagnoses, donor type (matched related, matched unrelated, mismatched related, mismatched unrelated), stem cell source (peripheral blood, umbilical cord, bone marrow), baseline liver, cardiac and renal function, and median follow-up time. However, more children in the low RBC transfusion event cohort had high Karnofsky/Lansky performance scores (83.5% vs 54.5%, p=0.001) and fewer had recurrent leukemia or other forms of advanced disease compared with the children more heavily transfused (41.8% vs 87.9%, p<0.0001). Results: No association was observed between high RBC transfusion exposure and TRM. High RBC transfusion events were associated with lower OS at 5 years in univariate analysis (38% versus 61%, p=0.04); in multivariate analysis, this association was not significant (hazard ratio=1.3, 95% confidence interval 0.7-2.5). Conclusion: Further studies in children are needed to investigate iron overload and HSCT outcomes.
Highlights
The generation of hydroxyl radicals catalyzed by non-transferrin bound iron (NTBI) and subsequent tissue damage is responsible for the toxicity of iron overload [1]
The only published study in pediatrics concluded that elevated ferritin (>1000 nanogram/milliliter [ng/mL]) due to pre-hematopoietic stem cell transplant (HSCT) redblood cell (RBC) transfusion events is independently predictive of transplant related mortality (TRM) and inferior overall survival (OS) in Korean children with hematologic malignancies [7]
We aim to investigate the association between iron load, as measured by a surrogate marker, number of pretransplantation RBC transfusions, and TRM and OS following HSCT in a heterogeneous group of pediatric patients with hematologic malignancies in the US
Summary
The generation of hydroxyl radicals catalyzed by non-transferrin bound iron (NTBI) and subsequent tissue damage is responsible for the toxicity of iron overload [1]. In adults with hematologic malignancies, pre-transplantation transfusional iron overload, as measured by serum ferritin, is independently associated with transplant related mortality (TRM) and inferior overall survival (OS) following hematopoietic stem cell transplantation (HSCT) [2,3,4,5,6]. We aim to investigate the association between iron load, as measured by a surrogate marker, number of pretransplantation RBC transfusions, and TRM and OS following HSCT in a heterogeneous group of pediatric patients with hematologic malignancies in the US. Recent studies have shown that an elevated ferritin level prior to hematopoietic stem cell transplant (HSCT), serving as a surrogate marker of body iron load, is independently associated with transplant related mortality (TRM) and inferior overall survival (OS) in adult oncology patients
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