Infectious diseases are important causes of morbidity and mortality in patients with cancer. In certain instances, the malignancy itself can predispose patients to severe or recurrent infections. Neutropenia has been recognized for many decades as a major risk factor for the development of infections in patients with cancer undergoing chemotherapy. Effective strategies to anticipate, prevent, and manage infectious complications in patients with cancer experiencing neutropenia have led to improved outcomes. Reflecting the heterogeneity of immunocompromised conditions in patients with cancer and the spectrum of pathogens to which they are susceptible, the NCCN expanded the scope of its panel in 2007 to create guidelines on “Prevention and Treatment of Cancer-Related Infections.” These revised guidelines replace the previous NCCN guidelines on “Fever and Neutropenia.” These guidelines characterize the major categories of immunologic deficits in persons with cancer and the major pathogens to which they are susceptible. Specific guidelines are provided on the prevention, diagnosis, and treatment of the major common and opportunistic infections that afflict patients with cancer.

Special Feature

Risk and Timing of Neutropenic Events in Adult Cancer Patients Receiving Chemotherapy: The Results of a Prospective Nationwide Study of Oncology Practice
Jeffrey Crawford, MD; David C. Dale, MD; Nicole M. Kuderer, MD; Eva Culakova, PhD; Marek S. Poniewierski, MD; Debra Wolff, MS, PCNP; and Gary H. Lyman, MD, MPH

This study was undertaken to describe the relationship between the occurrence and timing of neutropenic events and chemotherapy treatment in a community-based population of patients with cancer. The study included 2962 patients with breast, lung, colorectal, lymphoma, and ovarian cancers from a prospective U.S. registry of patients initiating a new chemotherapy regimen. Detailed patient-, disease-, and treatment-related data, including toxicities, were captured at baseline, the beginning of each cycle, and each midcycle blood draw for up to 4 cycles of treatment. Primary outcomes included febrile neutropenia (FN), severe neutropenia without fever/infection, and relative dose intensity (RDI). Thirty-seven percent of patients were aged 65 years or older, 43.5% had an Eastern Cooperative Oncology Group performance status of 1 or greater, and 27% had 1 or more comorbidities. Reductions in RDI to less than 85% of standard in the first cycle were planned in 23.6% of patients, whereas primary colony-stimulating factor prophylaxis was used in 18.2%. Despite frequent planned reductions from standard RDI, the incidence of FN remains high in community oncology practice in the United States. Improved methods of assessing patient risk factors for neutropenia before treatment are needed.

Featured Articles

Broad Spectrum Antifungal Prophylaxis in Patients with Cancer at High Risk for Invasive Mold Infections: Point
Antonio V. Gonzalez, MD; Andrew J. Ullmann, MD; Nikolaos G. Almyroudis, MD; and Brahm H. Segal, MD

Invasive fungal infections (IFIs) are a leading cause of infection-related mortality in patients with acute leukemia and prolonged neutropenia and in allogeneic hematopoietic stem cell (HSCT) transplant recipients with graft-versus-host disease (GVHD). The availability of broad-spectrum antifungal agents that can be safely administered over prolonged periods has stimulated interest in using mold-active prophylactic agents early as prophylaxis rather than later as therapy for suspected or documented IFIs. Two recent prospective, randomized trials have shown a clear benefit of posaconazole prophylaxis in patients with myelodysplastic syndrome and acute myelogenous leukemia with prolonged neutropenia and in allogeneic HSCT recipients with severe GVHD. In contrast, the strategy of pre-emptive antifungal therapy, in which yeast-active prophylaxis (fluconazole) or no antifungal prophylaxis is used initially and modifications are triggered by a combination of laboratory markers and chest computed tomography, is currently limited to an open-label feasibility study. The authors of this Point article believe that have sufficient evidence is not currently available that the net benefit of the pre-emptive approach is at least on a par with posaconazole prophylaxis in the specific patient groups that were studied.

Broad Spectrum Antifungal Prophylaxis in Patients with Cancer at High Risk for Invasive Mold Infections: Counterpoint
Johan Maertens, MD; Kristel Buvé, MD; and Elias Anaissie, MD

The management of invasive mold infections in patients with prolonged neutropenia and in hematopoietic stem cell transplant (HSCT) recipients with graft-versus-host disease (GVHD) has been hampered by the difficulty of diagnosing these infections, because definite diagnosis invariably centers on histologic identification of hyphae in tissue or on culture from a sterile body site. Therefore, most practitioners rely on prophylaxis and empirical therapy. However, emphasis is currently shifting from routine prophylaxis or empirical therapy to screening high-risk neutropenic patients so that clinicians can administer appropriate antifungal therapy early, when it can potentially improve patient outcome. Together with assessment of clinical signs, cultures, and computed tomography, these screens are useful for starting antifungal therapy pre-emptively and for monitoring the course of the disease and response to treatment. While awaiting further evaluation of these tools during the post-engraftment period of allogeneic HSCT, mold-active prophylaxis for patients with severe acute or chronic GVHD may be justified. Some critical issues must still be adequately addressed, however, including the generalizability of study results, impact of mucositis and gastrointestinal GVHD on drug bioavailability, need for therapeutic drug monitoring, impact on diagnostic assays, and optimal treatment of breakthrough IFIs.

Prevention and Early Treatment of Opportunistic Viral Infections in Patients With Leukemia and Allogeneic Stem Cell Transplantation Recipients
Michael Angarone, DO, and Michael G. Ison, MD

A leading complication of leukemia therapy and stem cell transplantation is opportunistic viral infections. Infections caused by cytomegalovirus, herpes simplex, varicella-zoster, Epstein-Barr, and the community respiratory viruses are associated with significant morbidity and mortality in this highly immunosuppressed population. Fortunately, a growing armamentarium is allowing more effective prophylaxis of these pathogens. This article reviews the epidemiology and prophylactic strategies available for these common opportunistic viral pathogens.

Infectious Complications Associated With Immunomodulating Monoclonal Antibodies Used in the Treatment of Hematologic Malignancy
Sophia Koo, MD, and Lindsey R. Baden, MD

Immunomodulating monoclonal antibodies are a relatively new addition to cancer therapeutics, and they have been shown to improve clinical outcomes in patients with a variety of hematologic malignancies. Because of their targeted nature, these agents are often believed to be less immunosuppressive than standard cytotoxic chemotherapeutic agents, but discerning a clear causal association between an immunomodulating therapy and its infectious sequelae is often difficult. Comorbid illness, intrinsic immunosuppression from the underlying malignancy, use in the salvage setting, and prior and concomitant use of immunosuppressive agents in this patient population can confuse the association. The authors of this review evaluate both better established and anecdotal infectious complications associated with the major immunomodulating therapies used in the hematologic malignancy and hematopoietic stem cell transplant setting, including rituximab, alemtuzumab, gemtuzumab ozogamicin, infliximab, dacluzimab, and basiliximab.

Influenza: Preparedness for an Inevitable “Emergency” for Oncology and BMT Units
John R. Wingard, MD

Influenza is a seasonal and pandemic threat to the general population, and its effects can be devastating for patients with cancer and those who have undergone blood and marrow transplantation (BMT). This impact can be minimized, however. Emergency preparedness is the key to mitigating the impact of influenza on the oncology and BMT services. Having a plan that provides a framework of preparedness and outlines steps to take in the event of a community outbreak is crucial. In the midst of an outbreak, the oncology and BMT teams should act to quickly identify patients with suspected infection, move infected patients and staff away from noninfected patients to prevent contact, and decide which patients require prevention or treatment with antiviral agents. Ongoing engagement by the entire team to evaluate the effectiveness of its actions and modify its plan as necessary will ensure success.

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