AIDS TREATMENT NEWS No. 110 - September 7, 1990
John S. James

In the August 15 issue of the Annals of Internal Medicine, researchers from the U.S. National Cancer Institute, and other branches of the National Institutes of Health, published a report on AZT therapy and incidence of non-Hodgkin's lymphoma[2]. While the figures on lymphoma are indeed alarming, we believe that a close look at the paper shows less reason to worry about AZT than first impressions might suggest.

Results

To obtain long-term data on AZT, the researchers analyzed all patient records from three early trials of the drug at the National Cancer Institute; the patients are among the first to use AZT. A total of 55 patients were included. Eight of them (14.5 percent) had developed a high-grade non-Hodgkin's B-cell (or in one case, null-cell) lymphoma, after a median of two years of AZT treatment. However, statistical projections were that 28.6 percent (of patients equally ill to begin with) would develop lymphoma by 30 months of AZT treatment, and 46.4 percent by three years. These figures do not apply to people who start AZT earlier, and at lower doses, today.

Clearly these results imply that lymphoma will become an increasingly serious problem. But in evaluating the risk of lymphoma, and especially the question of whether AZT has any role in causing it, other facts also presented in the paper must be considered:

* These eight patients had advanced illness before they began treatment with AZT. All had AIDS or symptomatic HIV infection, and their median T-helper count when they started treatment was 26 (range 8-135). Their median T-helper count when they developed lymphoma was six. All eight had less than 50 T-helper cells for at least five months (median time 15.3 months with a count under 50) before they developed lymphoma.

The median T-helper count for all 55 patients when they started treatment was 74 (range 0-973), compared to the median of 26 for the eight who developed lymphoma -- suggesting that those with higher T-helper counts did not develop lymphoma, although they also were taking AZT.

* These results must be considered in view of the fact that even before AIDS, and certainly before the use of AZT, it was well known that immune suppression due to other causes increased the risk of lymphoma. As of 1987, over 200 cases of non-Hodgkin's lymphoma were known among persons with hereditary immune deficiencies. In addition, patients using immune suppressing drugs to control rejection after organ transplants have a high incidence of cancers, and 36 percent of those cancers were found to be non-Hodgkin's lymphomas. Immune suppression is known to cause lymphomas, without AIDS or AZT being involved.

* The lymphomas found in this study were the same kind as those generally found in AIDS, whether or not patients are taking AZT. This suggests that immune deficiency, not AZT, is more likely the cause of the lymphoma.

* If AZT did contribute to causing lymphoma, large doses would probably be more dangerous than smaller ones. All the patients in this study started AZT early, when the recommended dose was 1200 mg per day. Today most patients are using half that much or less.

At this time there seems to be a consensus among most physicians and scientists that while AZT cannot be ruled out as a cause of lymphoma, it is much more likely that the increase in this cancer is because patients with serious immune deficiency are living longer. The possibility that AZT could help cause the disease must be investigated. But meanwhile, experts are not recommending changes in treatment as a result of this study, and we have not heard of any physicians changing their practices because of it.

Note: for an overview of treatments for lymphoma, see "Lymphoma Treatments Update," below.

References

1. Ziegler JL, Beckstead JA, Volberding PA, and others. Non-Hodgkin's lymphoma in 90 homosexual men. Relation to generalized lymphadenopathy and the acquired immunodeficiency syndrome. New England Journal of Medicine. 1984; volume 311, pages 567-570.

2. Pluda JM, Yarchoan R, Jaffe ES, and others. Development of non-Hodgkin's lymphoma in a cohort of patients with severe human immunodeficiency virus (HIV) infection on long-term antiretroviral therapy. Annals of Internal Medicine. August 15, 1990; volume 113, number 4, pages 276-282.

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