Is lymphoma occurring in the elderly the same disease?

The letter from Lim et al. in this issue of Leukemia and Lymphoma [1] addresses the most rapidly increasing problem in clinical oncology – i.e., the care of elderly patients. This increase is a reflection of the aging population in industrialized countries and the fact that most cancers occur more frequently with advancing age. Dealing with this problem involves several issues including the definition of ‘‘elderly, whether the same types of lymphoma occur in elderly patients, does the disease behave differently in the elderly, how do we measure treatment outcome in a group of patients who often have severe co morbidities and whose survival might be compromised for reasons other than the malignancy, and are the same treatments used in younger patients the best for this age group. ’’ For many of us who have been practicing hematology and oncology for decades, the definition of elderly is changing. As someone once said, ‘‘an elderly patient is someone five years older than me. ’’ However, there is some objective data to be applied to this issue. In lymphomas, as in a number of other malignancies, the age of 60 seems to be a turning point in survival. For example, the International Prognostic Index identified this as the age that survival appeared to decline with comparable treatments [2]. However, this does not take into account the extreme variability of the clinical status of patients over 60 years of age. It is certainly possible to have a patient with diabetes, renal failure, and coronary artery disease at age 45 who would be at a much higher risk for treatment than a healthy 69year-old with no comorbidities who exercises regularly. It would make sense, however, that as patients age beyond 60 years, their relative risk might increase. The data from Lim et al. suggest that the very elderly might pose special problems [1]. It has been known for a long time that subtypes of lymphoma do not all have the same age of occurrence. For example, Hodgkin disease has a bimodal age distribution of occurrence with peaks in both younger and older patients, Burkett lymphoma is relatively more common in younger patients, and diffuse large B-cell lymphoma and follicular lymphoma can occur at all ages but are most frequent in older patients. An International study of a new system of classification of non-Hodgkin lymphomas found that elderly patients were most likely to have diffuse large B-cell lymphoma, small lymphocytic lymphoma, and peripheral T-cell lymphoma when compared in to younger patients [3]. In a study from the Netherlands, the most frequent lymphoma in elderly patients was diffuse large B-cell lymphoma [4]. There is some evidence that the same histological subtype of lymphoma might not be exactly the same disease in older patients as in younger patients. If this is correct, the poorer outcome seen in older patients might reflect not only their poorer prognostic characteristics but also the existence of a more aggressive disease. Recently studies of the gene expression profile of diffuse large B-cell lymphoma have identified at least three subtypes, despite identical appearance under the microscope [5,6]. These subtypes have been labeled germinal center B-cell type, activated B-cell type, and mediastinal large B-cell lymphoma. The gene expression profile in the later subgroup is similar to that seen in classical Hodgkin disease [6,7]. The mediastinal large B-cell lymphoma subtype is seen much more often in younger patients with a median age of approximately 35 years. The germinal center B-cell type of diffuse large B-cell lymphoma occurs at a median age of approximately 8 years less than the activated B-cell