It is clinically useful to divide non-Hodgkin lymphomas (NHL) into indolent and aggressive based on their clinical behavior (1). Patients with indolent NHL typically have a survival of many years, even if untreated, but paradoxically are usually incurable. Patients with aggressive NHL have a survival time measured in weeks to months if untreated yet are usually chemosensitive and frequently curable. In this chapter, we focus on the clinical characteristics, pathology, and treatment of aggressive NHL.
The incidence of NHL has increased over the last five decades, as reported by US and international registries (2,3,4). During the years 1993 to 1995, the age-adjusted incidence increased 3% per year according to data from the Surveillance, Epidemiology, and End Results (SEER) program of the National Cancer Institute (2). Some of this increased incidence can be attributed to the acquired immunodeficiency syndrome (AIDS), but this epidemic does not explain the increase of NHL before 1980. In the elderly population, there has also been a marked increase of NHL, largely the indolent NHLs, which are discussed in Chapter 7.
An estimated 71,850 new cases of NHL will be diagnosed in the United States in 2015, and 19,790 NHL-related deaths will occur. In 2014, NHL was the ninth largest cause of death among men and the eighth largest cause in women (3% of all cancer-related deaths). Diffuse large B-cell lymphoma (DLBCL), the most common NHL subtype, has an aggressive behavior and is more common in whites than African Americans in the United States; however, 5-year survival outcomes are worse in African Americans (5).
Most cases of aggressive NHL do not have a well-defined cause. Recent work has shown that the lifetime risk for many cancers correlates with the total number of divisions of normal self-renewing cells (6). The implications of these findings suggest that many cancers may not be due to hereditable genetic aberrancies, environmental exposures, infectious etiologies, or other known causes, but instead are attributable to a combination of factors that may include chance. For the NHLs that appear to have currently identifiable drivers, there are four groups of drivers: immune suppression (both acquired and primary), infectious agents, toxic exposure, and familial (Table 8-1).
Table 8-1Risk Factors Associated With Aggressive Non-Hodgkin Lymphomas ||Download (.pdf) Table 8-1 Risk Factors Associated With Aggressive Non-Hodgkin Lymphomas
Inherited and acquired immune deficiency
X-linked immunoproliferative disorder
Severe combined immunodeficiency
Common variable immune deficiency
Iatrogenic immune suppression
Solid organ or bone marrow transplant
Radiation or radiation therapy
Human T-cell leukemia/lymphoma virus
Human herpesvirus type 8 (HHV-8)
Human immunodeficiency virus (HIV)
Systemic lupus ...