Non-Hodgkin’s lymphoma (NHL) is a heterogeneous group of lymphoproliferative disorders originating in B-lymphocytes, T-lymphocytes, or natural killer (NK) lymphocytes. In the United States, B-cell lymphomas represent 80% to 85% of the cases. An estimated 63,190 new cases of NHL, including 34,200 in men and 28,990 in women, will be diagnosed in 2007, and 18,660 deaths will occur. NHL is the fifth leading type of new cancer diagnosed and the ninth leading cause of cancer deaths among men and the seventh among women. The incidence of NHL increased dramatically between 1970 and 1995; this increase has been attributed partly to the HIV epidemic and the development of AIDS-related NHL. However, much of the increased incidence has been observed in patients in their sixth and seventh decades, and has largely paralleled a major decrease in mortality from other causes. The median age of individuals with NHL has risen in the past 2 decades. As a result, patients with NHL may also have significant comorbid conditions, which complicate treatment options. Important updates to these guidelines for 2008 include expanded second-line therapy options for patients with diffuse large B-cell lymphoma and peripheral T-cell lymphomas. In addition, the mycosis fungoides/Sézary syndrome section now includes pages on updated staging and classification systems and suggested treatment regimens.

Special Feature

Evidenced-Based Report on the Occurrence of Fatigue in Long-Term Cancer Survivors
Ilana M. Braun, MD; Donna B. Greenberg, MD; and William F. Pirl, MD

Although some cancer survivors report persistent fatigue years after treatment, little is known about the prevalence of this symptom compared with the general population. This article examines current evidence for the occurrence of fatigue in long-term cancer survivors through reviewing published population-based studies that incorporated controls from the general population. Using the search criteria “fatigue AND cancer survivors” in PubMed, the authors identified 16 articles (based on 15 cross-sectional datasets) comparing fatigue severities in survivors of adult cancers with those in the general population. A total of 8096 cancer survivors were examined across datasets. Most datasets focused on either breast cancer (7) or Hodgkin’s disease survivors (6). Nine articles (based on 8 datasets) showed statistically significant (P < .05) differences among groups; 4 articles showed negative results; and 3 showed both positive and negative results depending on fatigue dimension measured. Among the studies that reported scores for the fatigue subscale of the European Organization for Research and Treatment of Cancer Core Questionnaire for Quality of Life (most studies), mean fatigue levels in cancer survivors ranged from 28.7 to 36.5 out of an overall score of 100, and mean fatigue levels in matched general population controls ranged from 20 to 30 out of 100. Most effect sizes calculated were small. Fatigue was a burden to both cancer survivors and members of the general population. Although evidence for greater fatigue severity in cancer survivors was mixed, most studies reported greater fatigue in cancer survivors compared with controls. The magnitude of this effect was generally small. Inferences from the data were limited by variability in both the definition of survivor and the fatigue assessments, and by the cross-sectional design of the studies. Prospective longitudinal studies are needed to determine causal relationships between excessive fatigue and surviving cancer.

Featured Articles

Getting the Diagnosis Right in NHL: Role of Immunohistochemistry and Molecular Diagnostic Testing
Julie Teruya-Feldstein, MD

Challenges in diagnosing lymphoid neoplasms include their complex heterogeneity and that approximately 40 or more diseases exist. Immunophenotyping and molecular diagnostics have made important contributions to precise and accurate diagnoses. Strong interactions with clinical colleagues and meticulous attention at the microscope by expert hematopathologists are very important in making a correct diagnosis. Awareness of the literature and interactions has expanded understanding of these complex diseases, providing prognostic information that can ultimately assist in appropriate clinical management of patients or development of new targeted therapies. A precise lymphoma diagnosis therefore involves integration of clinical information, morphologic architectural and cytologic patterns, immunohistochemistry, cytogenetics, and molecular biology to ultimately allow identification of specific diseases, thereby implying prognostic significance and potential therapeutic targets. This article reviews recent published immunophenotypic diagnostic and biomarker studies, discusses molecular diagnostic expression profiling studies of the more common entities encountered in daily clinical practice, and references published summaries from the combined Society of Hematopathology and European Association for Haematopathology Workshops.

Beyond the Guidelines in the Treatment of Peripheral T-Cell Lymphoma: New Drug Development
Andy I. Chen, MD, PhD, and Ranjana H. Advani, MD

Peripheral T-cell lymphomas (PTCLs) are a rare and diverse group of neoplasms with poor prognosis. Management of these disorders has been largely extrapolated from the treatment of aggressive B-cell lymphomas; however, therapeutic responses to this approach are neither adequate nor durable for most patients with PTCL. Given the rarity of peripheral T-cell lymphoma, much of the literature consists of studies with small sample sizes and anecdotal case reports. Therefore, no consensus exists on the best therapeutic strategy for either newly diagnosed or relapsed/refractory PTCL. Investigation into the pathogenesis of PTCL has also identified new targets for treatment. These emerging therapies include new uses of existing agents and the development of novel agents specifically targeted against T-cell lymphoma. Because of the rarity and heterogeneity of PTCL, national and international cooperation is needed to conduct the clinical studies required for the development of more effective treatment paradigms. These efforts are ongoing and will hopefully guide new strategies to improve the historically poor outcome of PTCL.

Review of the Treatment of Mycosis Fungoides and Sézary Syndrome: A Stage-Based Approach
Steven M. Horwitz, MD; Madeleine Duvic, MD; Elise Olsen, MD; Pierliugi Piorcu, MD; and Youn Kim, MD

The NCCN Clinical Practice Guidelines in Oncology: Non-Hodgkin’s Disease were recently revised to include recommendations for treating mycosis fungoides and Sézary syndrome. These uncommon lymphomas require a specialized evaluation and use a unique TNMB staging system. Unlike the other forms of non-Hodgkin’s lymphomas, stage overwhelmingly determines prognosis and defines radically different treatment approaches. For patients with early-stage disease, initial treatment with skin-directed therapies is preferred and many patients never require systemic therapy. For patients with refractory or advanced-stage disease, biologic therapies are often the first choices, and chemotherapies are reserved for later in the disease course. Many milder therapies may be repeated several times in the disease course, and maintenance and tapering strategies are common. This article also discusses the emerging role of allogeneic stem cell transplantation.

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