Primary central nervous system (CNS) lymphoma continues to increase in incidence in the immunocompetent population. This persistent rise in incidence in this population is not explained by our improved ability to diagnose the tumor and, thus, remains a mystery.
The falling incidence of primary CNS lymphoma in patients with the acquired immune deficiency syndrome (AIDS) is encouraging. The introduction of more effective antiretroviral agents for the treatment of AIDS patients has resulted in a higher CD4 cell count. This supports the notion that CD4 cell immunity may play an important role in immune surveillance of the CNS. Reestablishment of a more adequate number of CD4 cells may explain, in part, the decreased incidence of this tumor in AIDS patients.
Radiation, Chemotherapy, and Multimodality Approaches
This thorough, timely, review by Nasir and DeAngelis on various aspects of primary CNS lymphoma in immunocompetent and immunodeficient patients brings into focus the roles of radiation therapy, chemotherapy, and multimodality therapy in the treatment of this condition. High-dose methotrexate(Drug information on methotrexate) followed by external-beam radiation, a therapeutic strategy pioneered by DeAngelis, is effective but quite toxic to patients over 60 years of age. This is a very important limitation in a disease for which the median patient age at diagnosis is 58 years.
Better strategies for drug treatment and radiation schemes are needed. Moreover, experience from therapeutic trials in systemic non-Hodgkins lymphomas strongly suggests that multidrug therapy will more likely succeed in producing durable remissions or even cures of these lymphomas.
As the authors note, a number of early clinical reports employing more than one agent, with or without blood-barrier disruption and intraarterial chemotherapy, have produced interesting responses. It is difficult to draw solid conclusions about the efficacy of these treatment schemes in larger patient populations from these early, small trials, however.
Need for Cooperative, Randomized Trials
In a disease that is as uncommon as primary CNS lymphoma, prospective, randomized, multicenter, cooperative clinical trials are needed to generate more successful therapeutic strategies. This is a rational approach because various questions can be raised and answered by cooperative trials, as has occurred in the fields of systemic lymphomas, primary brain tumors, and multiple sclerosis.[5-7]
Progress can be made by testing trial drugs in various combinations to arrive at decisive answers. This strategy will build on information gained from previous trials. Taking into account negative, as well as positive results, will lead to better design of future trials instead of a repetition of past mistakes.
This is a timely review of an important subject. Hopefully, the article will generate interest in future, multicenter, collaborative trials that have a large enough number of patients from which to draw solid conclusions and, thus, may lead to improvements in the care of patients with primary CNS lymphoma.