Although not a part of the current classification system for non-Hodgkin lymphomas (NHL), it is clinically useful to divide NHL into indolent, aggressive, and highly aggressive tumors (1). Patients with indolent NHL typically have a survival of several years, even if untreated, but paradoxically are usually incurable. Patients with aggressive NHL have a survival time measured in months if untreated, whereas patients with highly aggressive NHL have a survival of only weeks to a few months if untreated. However, both aggressive and highly aggressive NHLs are chemosensitive and are frequently curable. In this chapter, we focus on the clinical characteristics, pathology, and treatment of aggressive and highly aggressive NHL.
The incidence of NHL has increased significantly over the last five decades, as reported by United States and international registries (2–5). During the years 1993 to 1995, the age-adjusted incidence increased by 3% per year according to data from the Surveillance, Epidemiology, and End Results program of the National Cancer Institute (SEER) (3). There was also a concomitant increase in mortality during the same period. Some of this increased incidence can be attributed to the advent of the acquired immunodeficiency syndrome (AIDS), but that does not explain the increase of NHL prior to 1980. There has also been a marked increase of NHL in the elderly population (5). However, it is indolent NHLs that have increased most substantially in this group. These are discussed in another chapter.
An estimated 65,980 new cases of NHL will be diagnosed in the United States in 2009, and 20,790 NHL-related deaths will occur. These are estimated to be the ninth largest cause of death among US men, and the sixth in women in 2009 (3 and 4% of cancer-related deaths, respectively) (6). There is a higher incidence among Caucasians than African Americans in the United States, especially among the elderly, but recent increases in the incidence among younger cohorts of African Americans have been noted (5). A lower incidence is also seen among other American racial subgroups. Although almost all histologic types of NHL have increased in incidence over the last 20 years, the relative frequency of aggressive and highly aggressive NHL has remained relatively stable.
The causes or risk factors for NHL can generally be divided into four groups: immune suppression (both acquired and primary), infectious agents, toxic exposure, and familial (Table 8-1).
Table 8–1. Risk Factors Associated with Aggressive Non-Hodgkin Lymphomas |Favorite Table|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)|