Disorders of Blood Cell Production in Clinical Oncology
Summary of Key Points
• Anemia is very common in patients with cancer and is multifactorial.
• The anemia of persons with chronic disease is associated with decreased absorption of oral iron and decreased ability to access storage iron pools.
• Iron-restricted erythropoiesis may limit the efficacy of erythropoietic agents for the treatment of anemia in these patients and can be overcome with parenteral iron.
• Treatment of anemia in patients with cancer reduces transfusions and symptoms of anemia.
• Erythropoietic agent therapy is associated with an increased risk of venous thromboembolism.
• Neutropenia in patients with cancer is usually due to treatment.
• Myeloid growth factors can be used to reduce infection risk in patients for whom the risk is significant, and use of these growth factors is preferable to delaying or reducing the dose of chemotherapy when prolonging life is the intent.
• New agents for the stimulation of platelet production are in clinical development.
• Biosimilar preparations for commonly utilized hematopoietic growth factors will be appearing on the U.S. market. It will be important for oncologists to participate responsibly in postmarketing surveillance programs.
1. The anemia of chronic illness is usually associated with:
A A relatively low reticulocyte count
B Increased gastrointestinal absorption of dietary iron or supplemental oral iron
2. In randomized, controlled clinical trials, therapy with myeloid growth factors has been shown to:
A Decrease the incidence of febrile neutropenia during myelosuppressive chemotherapy
B Substantially improve outcomes when given to patients with uncomplicated, established febrile neutropenia who are undergoing chemotherapy
C Improve cure rates for patients with cancer who are receiving chemotherapy with curative intent
3. Administration of erythropoiesis-stimulating agents (ESAs) to anemic patients with cancer who are receiving myelosuppressive chemotherapy:
A Decreases the incidence of red blood cell transfusions
C Increases the incidence of venous thrombosis
D Decreases the chances that iron-restricted erythropoiesis will occur
4. As patents on ESA innovator molecules expire in the United States, biosimilar agents are expected to enter the market. Biosimilar cloned proteins, compared with the current innovator molecules, can be safely assumed to:
1. Answer: E. The anemia of chronic illness, also known as the anemia of inflammation, is associated with increases in serum hepcidin levels. Hepcidin decreases the number of functional ferroportin molecules that are critical for both gastrointestinal iron absorption and mobilization of iron from storage pools, resulting in iron-restricted erythropoiesis and a hypoproliferative anemia.
2. Answer: A. In randomized trials, filgrastim and pegfilgrastim have been consistently shown to decrease the risk of febrile neutropenia during chemotherapy when initiated before the onset of neutropenia. They have not been shown to decrease length of stay or antibiotic use when given once febrile neutropenia has occurred. Although evidence shows that myeloid growth factors increase the proportion of chemotherapy cycles that can be administered in full dose and on time and it is reasonable to infer that administering the full dose on time is very desirable when cure is the goal, improvement in survival has not been documented in a randomized trial. Randomized trials have not shown an impact on relapse risk or survival in patients with acute leukemia.
3. Answer: E. ESAs both decrease transfusion risk and increase thrombosis rates. Although the effect of ESAs on cancer survival remains controversial, there is no evidence that as currently utilized, they increase the survival of patients with cancer who undergo chemotherapy. ESAs place additional demands for iron on the erythron, which can result in functional iron deficiency and a blunt ESA response. This increase in iron-restricted erythropoiesis can be at least partially overcome by cotherapy with parenteral iron.
4. Answer: A. Because of posttranslational modifications that vary with different production techniques, different preparations will have different glycosylation and tertiary structure and hence immunogenicity. It will be important for physicians using these molecules to be aware of this factor.
