Blood Conservation and Chemotherapy-Induced Anemia: From Evidence-Based Guidelines to Clinical Practice
David S. Ettinger, MD, FACP, FCCP,* and Edward J. Norris, MD, MBA, FAHA†
Quite different from cancer treatment of yesteryear that aimed to merely slow tumor growth, today’s chemotherapy is fortunately saving lives and extending survival in countless people living with cancer. But it is also important to acknowledge that these modern-day regimens are often more dose and schedule intense, employed more often frequently in patients who in the past would have been solely treated with surgery, and are often supplemented with newer biologic agents (eg, monoclonal antibodies, small molecules as targeted therapy, and immunomodulatory agents). As a result of this increasingly aggressive and complex approach to the management of many different types of cancer, the myelosuppressive consequences of treatment, particularly chemotherapy-induced anemia (CIA), have become a major focus of supportive care in oncology.
Anemia is a frequent complication of myelosuppressive chemotherapy, with an incidence that ranges between 70% and 90%, depending on factors, such as cancer type and the chemotherapy regimen used.1 Left untreated, anemia may lead to a multitude of symptoms (eg, fatigue, tachycardia, cognitive impairment, shortness of breath, depression, and dizziness), have an adverse impact on comorbid conditions (eg, cardiac and pulmonary disease) and mortality, and lead to chemotherapy dose reductions and administration delays. The economic burden of anemia is substantial, with costs of untreated anemia arising from lost wages, increased hospitalization stays, and increased morbidity and mortality. As a result of these consequences, timely diagnosis and correction of CIA is essential, and is addressed by regularly updated guidelines released by several organizations, such as the American Society of Clinical Oncology, the American Society of Hematology, and the National Comprehensive Cancer Network.
Although some of the basic guideline recommendations (eg, diagnosis and assessment) have not changed markedly over the last several years, many of the key therapeutic positions have been significantly revised, primarily as a result of emerging studies addressing the safety of erythropoiesis-stimulating agents (ESAs) and the accompanying regulatory/labeling changes. As a reflection of these events, there has been renewed interest in the risks and benefits of blood transfusions and the use of blood conservation strategies.
For clinicians involved in oncology supportive care services, it is critical to stay abreast of all the recent developments that have taken place in the management of CIA, and as such, this issue of Johns Hopkins Advanced Studies in Medicine is dedicated to providing the latest data and guideline recommendations pertaining to the various therapeutic options available for CIA. George M. Rodgers, III, MD, PhD, opens the discussion with a review of the prevalence and etiology of CIA, citing traditional cytotoxic drugs (eg, cisplatin, carboplatin, taxanes, vinorelbine, and topotecan), new biologic agents, and other factors (eg, radiation, repeated chemotherapy cycles, and dose intensity) that impact the incidence and severity of the condition. Dr Rodgers also explores the risks and benefits of current treatments (packed red blood cell transfusions, ESAs, and iron supplementation), in addition to therapeutic recommendations from several recently updated guidelines on the management of CIA.
Charles L. Bennett, MD, PhD, MPP, Athena T. Samaras, BA, and Stephen Y. Lai, MD, PhD, center their discussion on the impact of recent studies questioning the safety of ESA therapy on transfusion utilization patterns in the United States and abroad. Dr Bennett and colleagues explore various utilization studies (in Europe, Canada, and the United States) relating to the complex relationship between ESA regulatory and reimbursement actions, patterns of ESA use, and transfusion practices. They find that, generally, ESAs are used more frequently in the United States than in Europe, where the approach has been to administer ESAs or to transfuse patients with CIA who were symptomatic, rather than those who would potentially require a transfusion in the future. Also included in this article are factors to consider in identifying patients with CIA at risk for blood transfusion.
Lawrence Tim Goodnough, MD, and Aryeh Shander, MD, FCCM, FCCP, focus their discussion on risks and complications of allogenic blood transfusions, acknowledging that although today’s blood supply is safer than ever from various pathogens, infectious risks have not been completely eliminated because of limitations in current detection methods and the potential risk of emerging pathogens. Dr Goodnough and Dr Shander offer a considerable review of both infectious and noninfectious risks of transfusion, in addition to strategies used to ensure the safe and appropriate use of blood and blood products.
Aryeh Shander, MD, FCCM, FCCP, also authors an article on blood conservation strategies, which include various pharmacologic agents (ESAs, antifibrinolytics, and recombinant activated factor VII), as well as numerous devices and techniques (eg, acute normovolemic hemodiluton) used to minimize or avoid the use of allogenic blood transfusion. Dr Shander explores the current supporting evidence, which comes primarily from studies examining these treatments perioperatively, in critical care and trauma settings, and in those with congenital bleeding disorders. Also included is a discussion on areas of controversy related to blood conservation and examples of successful institution-based blood management programs.
For clinicians who manage patients with CIA, it is perhaps an uncertain time and, therefore, it is vital to stay informed on all the emerging studies and the resultant changes to guideline ecommendations when making clinical decisions.
1. Groopman JE, Itri LM. Chemotherapy-induced anemia in adults: incidence and treatment. J Natl Cancer Inst. 1999;91:1616-1634.
*Alex Grass Professor of Oncology, The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, Maryland.
†Associate Professor, Department of Anesthesiology and Critical Care Medicine, Director, Vascular Anesthesia, The Johns Hopkins University School of Medicine, Baltimore, Maryland.
Address correspondence to: David S. Ettinger, MD, FACP, FCCP, Alex Grass Professor of Oncology, The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Bunting-Blaustein Cancer Research Building, G88, 1650 Orleans Street, Baltimore, MD 21231. E-mail: firstname.lastname@example.org.
The content in this monograph was developed with the assistance of a staff medical writer. Each author had final approval of his or her article and all its contents.