Iron Overload in Bone Marrow Transplant Recipients in two Brazilian Centers: An Analysis based on Ferritin and Transferrin Saturation

Background: Hematopoietic Stem cell Transplant Recipient conditioning regimens include immunosuppressive and myeloablative drugs that cause secondary cell damage and lead to ineffective erythropoiesis, which is one of the mechanisms that triggers iron (Fe) overload (IO). In addition, exogenous Fe from transfused blood components, specifically red blood cells, is what most contributes to excess Fe in the body. Fe toxicity secondary to transfusion is complex to estimate as it is related to the sum of exposure time and exogenous Fe associated with the factors determined based on the environment, genetic metal transport differences, and intrinsic antioxidant defenses. Objective: This study aimed to assess the impact of IO on HSCT in terms of overall survival (OS), in addition its relationship with red blood cell transfusion support, using serum biomarkers as ferritin and transferrin saturation. Materials and Methods: A specific laboratorial and clinical data was collected in as ample of 199 bone marrow recipients from two public hospitals at São Paulo, Brazil, in a large period, submitted to allogeneic Hematopoietic stem cell transplantation, between 1996 to 2018.Results:Data analysis showed that the highest mean ferritin levels in absolute numbers was reached within 100 days after HSCT in 146 (73.4%) patients, followed by a second peak in the ferritin levels in 44 (22.3%) patients 1 year after HSCT, with significantly decreased ferritin levels obtained in subsequent measurements. The sample presented higher TSI 100 days post-transplant, with a mean TSI of 46.93%. This finding correlates with the higher peak ferritin concentration in the same post-transplant period. OS was impacted by the number of red blood cell transfusions; the group with the lowest number of transfusions (<10) achieved greater survival. The study also demonstrated that a mean ferritin level of >1,000 post-HSCT impacted the patient’s OS (79% versus 91%; p<0,05). We demonstrated that patients with a TSI of >50% have a lower OS, especially when evaluated after 1 year (80%: TSI > 50% versus 92%: TSI < 50%, p < 0.05).Conclusion: High ferritin and TSI levels cannot be attributed only to transfusion dependence, highlighting that the ferritin level remains high for up to 5 years, even if hemotherapy support is not required. Others factor must be evaluated in further studies to elucidate other mechanisms responsible for iron overload in bone marrow transplantation field.

The authors declare no conflict of interest.

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The datasets used in this study are openly available at [repository link] and the source code is available on GitHub at [GitHub link].

This work did not receive any external funding.