Bone Marrow Toxicity: Red Blood Cells

  • Pere GasconEmail author


Anemia is a common manifestation in patients with cancer. Its cause can be multifactorial: the cancer itself, chemotherapy treatments, infiltration of bone marrow by cancer cells, hemolysis, nutritional deficiencies, blood loss, inflammation, and so forth. A major consequence of anemia is fatigue, a symptom that impacts the quality of life of cancer patients, and it can also compromise patients’ compliance with their treatments. A new generation of anticancer agents, antitargeted therapies, is widely used in oncology. Some of these new agents are associated with anemia, although their mechanism is not yet understood.

We now have different options to correct chemotherapy- or cancer treatment-induced anemia: red blood cell (RBC) transfusions, iron, and erythropoiesis-stimulating agents (ESAs). Their safety profile is good if we know when and how to administer them.

Red blood cell transfusions are reserved for critical situations, when the patient presents with symptomatic severe anemia. In addition to the possibility that the RBCs carry viruses and other pathogens, some new alarm signals associated with their use have been raised over the last few years and are currently being investigated. Of particular concern are RBCs that have been stored for more than 2 weeks in the blood banks. Apparently, they lose some of their oxygen-carrying capacity and their ability to cross the capillaries.

Iron has long been an agent used to correct the anemia of blood loss. Recently, however, the administration of intravenous iron has become more popular, because the new preparations do not provoke the allergic and anaphylactic reactions seen with the old preparations. Intravenous iron is now being used in combination with ESAs to produce faster and more robust corrections of anemia in the so-called functional iron deficiency, a type of anemia associated with chronic diseases and inflammation. In this condition there is a need for soluble iron, because one of the factors released during inflammation is hepcidin, a peptide that blocks the absorption of oral iron in the duodenum.

Finally, oncologists can utilize ESAs (recombinant human erythropoietin) for chemotherapy-induced anemia. Although they have been used for more than 20 years, over the last 8 years, several alarm signals have been associated with them. Their safety has been questioned after few clinical trial publications reported a poor outcome in patients receiving these agents in comparison to the control arm without ESAs. Many hypotheses have been suggested: ESAs would promote tumor growth via the presence of EPO receptors in cancer cells, a fact seriously questioned by recent publications; ESAs induce thromboembolic events; and so on. Another adverse event associated with the use of ESAs is pure red cell aplasia, in which the ESA molecule undergoes some structural changes due to physical or chemical conditions, causing the development of anti-EPO antibodies. This situation has been described only in patients with chronic renal failure receiving ESAs. The latest meta-analysis on ESAs regarding adverse events concludes that as long as ESAs are being used according to registry specifications in the setting of chemotherapy-induced anemia and the level of hemoglobin does not go beyond 12 g/dL, their use is safe.


Anemia Red blood cell transfusions Iron Erythropoiesis-stimulating agents Adverse events Pure red cell aplasia Erythropoietin Thromboembolic events 


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Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Division of Medical Oncology, Department of Hematology-OncologyInstitut Clinic de Malalties Hemato-Oncologiques, University of BarcelonaBarcelonaSpain

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