Re: Blood transfusions and the risk of intermediate- or high-grade non-Hodgkin's lymphoma.

The incidence of non-Hodgkin’s lymphomas (NHLs) has increased for the past 30 years among men and women of all ages (1). A number of epidemiologic studies have been undertaken to determine the causes of this increase. In several studies (2–5), prior history of blood transfusion has been associated with an increased risk of NHL. This increased risk has been attributed to the immunosuppressive effects of allogeneic blood transfusions as well as the increased susceptibility of those persons who receive transfusions to infections caused by blood-borne organisms (3). A recent study (6) conducted in Sweden found no association between blood transfusion and risk of NHL. To address this issue, along with other NHL-related issues, we conducted a population-based, case–control study of NHL in two groups of subjects—those who were infected with the human immunodeficiency virus (HIV) and those who were not. Patients who were aged 18–75 years when they were newly diagnosed with highor intermediate-grade NHL [classified according to the Working Formulation (7)] and who lived in Los Angeles County were identified by the Cancer Surveillance Program, the populationbased cancer registry for Los Angeles County. Because the study’s major focus was acquired immunodeficiency syndrome (AIDS)–NHL, we limited case eligibility to patients with highor intermediate-grade lymphoma. Our study methods have been described previously (8,9). Briefly, we identified 1431 potentially eligible patients diagnosed between April 1989 and November 1992 and completed interviews with 525. We were unable to interview (and, hence, excluded) the remaining patients for the following reasons: 658 as a result of death, 44 for being too ill, two for being mentally incapacitated, 145 because of patient refusals, and 57 because of physician refusals for patient contact. Twenty-seven of the interviewed patients were ineligible based on pathology review and were excluded. Of the remaining 498 patients, 378 patients with NHL (193 females and 185 males) were confirmed to be HIV seronegative by standard HIV blood testing procedures. These patients were compared with neighborhood control subjects individually matched by age, race, and sex. Among the 120 seropositive patients with highor intermediate-grade NHL, 113 were homosexual or bisexual men. Men who were patients diagnosed with AIDS on the basis of factors other than NHL (and who were identified by the Los Angeles County AIDS Program and were treated at Los Angeles County–University of Southern California Medical Center) were selected as control subjects for the first 50 of the 113 patients with AIDS–NHL. These AIDS control subjects were matched to patients with AIDS–NHL by age, race, and method of HIV acquisition. Because of limited resources, we could not match additional AIDS control subjects to our patients with AIDS–NHL. The 50 matched AIDS case–control pairs form the basis of the AIDS–NHL analyses. Signed, informed consent was obtained from each subject, and study procedures were approved by the Los Angeles County–University of Southern California Institutional Review Board in accordance with assurances approved by the U.S. Department of Health and Human Services. We estimated odds ratios (ORs) and their 95% confidence intervals (CIs) using conditional logistic regression methods. Because previous analyses of the HIV-negative case patients and control subjects showed an association between NHL risk and history of recreational drug use (9), we conducted analyses that adjusted for use of these drugs. This study provides no statistically significant evidence to support the hypothesis that past history of blood transfusion is associated with an increased risk of highor intermediate-grade NHL (Table 1), although—based on the upper 95% confidence limit for the adjusted OR—we cannot exclude the possibility of a relatively small (72%) increase in risk of NHL among HIV-negative individuals or a nearly fivefold increase in risk among HIV-infected patients with AIDS. Following exclusion of subjects with a recent transfusion (any that occurred within 3 years of the date of the case patient’s NHL diagnosis date, for each case–control pair), a possible increased risk for AIDS–NHL remained among HIV-positive subjects who underwent a transfusion (five case patients and one control subject exposed), but this increased risk of NHL was not confirmed among the HIV-negative subjects. Multiple transfusion episodes were not associated with greater risk of NHL. Among HIV-negative subjects, results were similar when males and females were examined separately (data not shown). When all 113 AIDS–NHL case patients were compared with the 50 AIDS control subjects, the results were similar to those for the 50 matched pairs shown in the table (data not shown). As discussed by others (10), all such studies are potentially confounded by the underlying illnesses for which transfusions are given. It is also possible that receiving a blood transfusion, especially in the late 1970s to early 1980s, may have increased a patient’s likelihood of exposure to HIV. Thus, in the study of Blomberg and colleagues (5), in which blood transfusions were given during 1981–1982, of the seven patients who developed NHL, three developed extranodal high-grade NHL, a disease type that is particularly associated with AIDS (11,12). This is also relevant when considering the elevated risk of high-grade