RE: "BLOOD TRANSFUSIONS AS A RISK FACTOR FOR NON-HODGKIN’S LYMPHOMA IN THE SAN FRANCISCO BAY AREA: A POPULATION-BASED STUDY"

Jingcai Zhu1, Kangmin Zhu1, Robert S. Levine2 and Lee S. Caplan3

1 Department of Health Evaluation Sciences, Pennsylvania State University College of Medicine, Hershey, PA 17033.
2 Department of Family and Community Medicine, Meharry Medical College, Nashville, TN 37208.
3 Department of Community Health and Preventive Medicine, Morehouse School of Medicine, Atlanta, GA 30310.

We read with great interest the recent article on non-Hodgkin’s lymphoma (NHL) by Drs. Chow and Holly (1), in which no transfusion-NHL association was reported after transfusions in the past year of the study were excluded. This study, in conjunction with another recent investigation which found that an increased risk of NHL was associated with only blood transfusions received within 3 months of NHL diagnosis (2), implies the importance of excluding patients with recent transfusions in etiologic research on NHL. To demonstrate further the effect of recent transfusions, we analyzed data from the Selected Cancers Study, which enrolled a large number of NHL cases and collected information on the time of the last transfusion (in contrast to the time since first transfusion in previous studies) and many other factors.

Cases were 1,511 men aged 31–59 years who were diagnosed with NHL during 1984–1988 and identified through eight US cancer registries (Atlanta, Georgia; Detroit, Michigan; San Francisco, California; Seattle, Washington; Miami, Florida; Connecticut; Iowa; and Kansas). Controls were men who were frequency matched to lymphoma cases by cancer registry and age (n = 1,910). Information on risk factors was collected through telephone interviews. Questions pertaining to blood transfusions included the following: "At any time, since 1978, have you ever received a blood transfusion?" and "In what year did you last receive a transfusion?" Since some time did elapse between NHL diagnosis and interview, some study subjects might have included transfusions received after the NHL diagnosis was made. Because only the year of transfusion was known, we excluded men whose last transfusion occurred in the year after the NHL diagnosis. We also repeated analyses, excluding cases diagnosed with NHL between January and September, if the last transfusion and NHL diagnosis occurred in the same year, reasoning that the remaining cases were less likely to have had a transfusion as part of NHL treatment following diagnosis in the same year. We also confined our analyses to low-grade NHL, because patients with low-grade NHL are less likely to receive blood transfusions as a part of treatment than patients with high-grade NHL. In practice, a "watch and wait" approach is commonly taken for low-grade tumors (3). Patients with acquired immunodeficiency syndrome were also excluded from the analyses.

Our results showed that men who received blood transfusions were four times as likely to be diagnosed with NHL (95 percent confidence interval (CI): 2.9, 5.5) as those without transfusions after control for potential confounders. However, the increased odds ratio was observed only when the last transfusion occurred within 1 year of the diagnosis date (odds ratio = 70.9, 95 percent CI: 22.3, 225.7). When men who were diagnosed between January and September were excluded, the odds ratio for all transfusions decreased to 1.2 (95 percent CI: 0.8, 1.8). However, the risk for most recent transfusion within 1 year was still high relative to no transfusion (odds ratio = 9.7, 95 percent CI: 2.7, 34.3). When we repeated the analyses for low-grade tumors diagnosed between October and December, the corresponding odds ratio estimates were 1.0 (95 percent CI: 0.5, 1.8) for having ever had a transfusion and 11.1 (95 percent CI: 2.5, 49.9) for having had the last transfusion within the preceding year. No association was found for last transfusions accepted more than 1 year before the NHL diagnosis.

Our findings that the association between NHL and blood transfusions was driven by transfusions occurring within 1 year of diagnosis suggest that blood transfusions are not associated with NHL etiologically. This association might imply that blood transfusions are part of the treatment for early, prediagnostic manifestations of NHL, or that blood transfusions for treatment of other diseases increase detection of NHL. Therefore, it is important to exclude transfusions within 1 year in studies of blood transfusions as a risk factor for NHL.

Editor’s note: In accordance with Journal policy, Dr. Holly was asked if the authors wished to respond to the letter by Zhu et al. but chose not to do so.

REFERENCES

  1. Chow EJ, Holly EA. Blood transfusions as a risk factor for non-Hodgkin’s lymphoma in the San Francisco Bay area: a population-based study. Am J Epidemiol 2002;155:725–31.[Abstract/Free Full Text]
  2. Tavani A, Soler M, La Vecchia C, et al. Re: Blood transfusions and the risk of intermediate- or high-grade non-Hodgkin’s lymphoma. (Letter). J Natl Cancer Inst 1998;91:1332–3.[ISI]
  3. Multani P, White CA, Grillo-Lopez A. Non-Hodgkin’s lymphoma: review of conventional treatments. Curr Pharm Biotechnol 2001;2:279–91.[Medline]




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