Chronic lymphocytic leukemia and acquired disorders affecting the immune system: a case-control study.

The relationship of a number of subacute or chronic infectious diseases, connective tissue or autoimmune disorders, allergic conditions, and surgical excision of lymphoid tissue with chronic lymphocytic leukemia (CLL) was examined in a case-control study involving 342 cases and 342 matched controls. In both analyses of all matched pairs and those pairs in which both subjects were respondents, no statistically significant association was found between a history of subacute viral infections or subacute and chronic bacterial infections and CLL. Connective tissue or autoimmune disorders also were found not to be associated with CLL. Examination of the association between several allergic conditions and CLL suggested a protective effect as did a "dose-response" analysis, although none of the individual disorders showed a statistically significant relationship; however, a test for linear trend was significant (P = .04). Similarly, examination of the relationship between surgical excision of lymphoid tissue in several anatomic locations and CLL showed a protective effect, statistically significant for tonsillectomy-adenoidectomy (odds ratio = 0.69; 95% confidence interval = 0.48, 0.98). A statistically significant negative dose-response relationship, substantiating the protectiveness of the effect, was found.

Incidence of aplastic anemia in a three county area in South Carolina.

An apparent cluster of four aplastic anemia (AA) cases in teenagers residing in a small South Carolina town was further investigated. Incidence of AA in all age groups in a surrounding three county area (TCA) over a 12-year time interval was determined and compared with AA incidence rates in Baltimore, representing the only known population based United States incidence data. The same general age-specific incidence pattern (based on 27 cases in the TCA and 118 in Baltimore) was found in the two areas, both overall and for the four race-sex groups. Although based on small numbers, nonwhite average annual age-adjusted rates for males and females were higher in the TCA (6.8 and 13.7 per million) than in Baltimore (4.7 and 7.3). For whites, TCA rates were 11.7 and 5.4 (for males and females) and Baltimore rates were 7.1 and 5.4. The differences for non-whites in the two areas may indicate a greater prevalence of risk factors for AA in the TCA than in Baltimore, but the small numbers of cases and the lack of comparable data from other areas of the country, together with the possibility of misdiagnosis of the disease, make definitive conclusions impossible.

Serum protein electrophoresis patterns in chronic lymphocytic leukemia. Clinical and epidemiologic correlations.

Serum protein electrophoresis (SPEP) data obtained at diagnosis were available for 98 of 342 patients with chronic lymphocytic leukemia (CLL) identified in a population-based case-control epidemiologic study. Patients tested with SPEP at diagnosis were significantly younger, more likely to have lymphadenopathy, and more likely to have had their conditions diagnosed at a university hospital than those not tested. Four categories of electrophoretic patterns were identified: normal (N = 56), hypogammaglobulinemia (N = 28), hypergammaglobulinemia (N = 11), and monoclonal gammopathy (N = 3). A higher proportion of those with hypergammaglobulinemia were black, and patients with hypergammaglobulinemia and monoclonal gammopathy were more likely to die within the first year following diagnosis than patients in the other SPEP groups. No association was found, however, between SPEP pattern and a clinical staging classification for CLL. These findings suggest that SPEP may be a useful adjunct in categorizing possible subtypes of CLL and developing future clinical staging classifications.

An apparent cluster of aplastic anemia in a small population of teenagers.

Four teenagers with severe aplastic anemia, initially diagnosed and evaluated over a seven-year period at The Johns Hopkins Bone Marrow Transplant Unit, Baltimore, were residents of the same small town in South Carolina. Estimated annual incidence for that age group in the town, based on the four cases, was 100 times the expected rate. All four of the teenagers had attended one of two junior high schools. An exploratory survey of all high-school students, comparing risk factors of those who had attended the "affected" junior high school with those who had attended the "unaffected" junior high school, showed no associations with exposure to glue, paint or varnishes, pesticides, history of hepatitis or infectious mononucleosis, or use of chloramphenicol or other suspected drugs. Weak associations were found between the affected junior high school and employment in the textile industry and in agriculture (specifically peach orchards).

A comparison of interview data and medical records for previous medical conditions and surgery.

Although interview information is usually the sole source of data in case-control studies, the accuracy of such data is infrequently assessed. We compared interview data on selected medical conditions and surgical procedures with medical records of subjects with chronic lymphocytic leukemia. We examined agreement by type of respondent (self or surrogate), age, sex, race, and type of hospital. The strength of agreement between the two data sources (as measured by kappa statistics) was substantial kappa greater than 0.6) for splenectomy, appendectomy, asthma, and systemic lupus erythematosus; moderate kappa greater than 0.4) for tonsillectomy/adenoidectomy, tuberculosis, diverticulitis, hepatitis, rheumatic fever, and drug allergy; and poor kappa less than 0.3) for chronic bronchitis, chronic sinusitis, psoriasis, rheumatoid arthritis, and most other types of allergy. In general, self respondents had more accurate recall than surrogate respondents. Among self respondents the strength of agreement tended to be greater for males than females, for whites than blacks, and for subjects from referral hospitals than for community hospitals. No consistent patterns were apparent by age. Despite a number of limitations, the findings of the study provide an addition to the scant epidemiologic literature on this topic, and suggest that for certain conditions medical record data collection may be needed to supplement interview information.

Comparison of methods for determining occupational exposure in a case-control interview study of chronic lymphocytic leukemia.

A comparison was made between two indirect methods for linking reported lifetime occupations and industries of employment with specific exposures and with directly reported exposure information, using data from a population-based case-control interview study of chronic lymphocytic leukemia (CLL). Exposures previously suspected of being associated with CLL were examined using a job-exposure matrix developed by Hoar et al and a linkage between observed occupational exposures and specific occupations, by industry, based on data collected in the National Occupational Hazard Survey (NOHS). In general, concordance on exposure for the two occupation-exposure linkage methods was fairly poor, although it was better for some of the exposures studied (butadiene and asbestos, for which most kappas were between 0.40 and 0.60) than for others (carbon tetrachloride and benzene with kappas ranging from 0.01 to 0.12). Higher proportions of cases and controls directly reported exposure to benzene and asbestos than was determined using the two more indirect methods, neither of which showed consistently greater agreement with direct reporting.

HLA antigens in chronic lymphocytic leukemia.

HLA-A, B, and C phenotypes of 88 white and 14 black patients with chronic lymphocytic leukemia (CLL) were compared with those of 3761 white and 660 black laboratory population controls, and HLA-DR phenotypes were compared with 742 white and 236 black controls from the same population. Several statistically significant associations were found, one of which (a strongly positive association with Cw6 for whites) persisted after correction for the number of antigens tested.

Cause-specific mortality coding. methods in the collaborative ocular melanoma study coms report no. 14.

Ascertainment of cause of death is often sought in clinical trials in which mortality is an outcome of interest. Standardized methods of coding all-cause and disease-specific mortality were developed and evaluated in the Collaborative Ocular Melanoma Study randomized trial of pre-enucleation radiation of large choroidal melanoma. All available clinical and pathologic materials documenting events prior to each reported death were reviewed systematically by a Mortality Coding Committee (MCC) to determine whether melanoma metastasis or local recurrence was present at the time of death. A level of certainty was assigned based on availability of local or central review of pathology materials. The outcome of the mortality coding protocol was evaluated both by assessing agreement between the judgment of the MCC and the presumed cause of death reported by the clinical center and, for a subset of patients, by assessing agreement between the MCC classification and the cause of death reported on the death certificate. As of July 31, 1997 (the cutoff date for the initial mortality report), 435 (95%) of 457 deceased patient files had been reviewed. The MCC classified 269 patients (62%) as dead with melanoma metastasis, 22 (5%) as dead with another malignant tumor, and 92 (21%) as dead with a malignant tumor of uncertain origin. Thirty-eight patients (9%) died with no evidence of malignancy; in 14 cases (3%), the presence or absence of malignancy could not be established due to lack of clinical information. Fair agreement (kappa = 0.34) was observed between the determinations of the MCC based on detailed review of materials and the cause of death reported on the death certificate, but death certificates alone underestimated the proportion of deaths due to metastatic choroidal melanoma. Detailed mortality coding identified difficulties associated with accurate reporting of cause-specific mortality in patients with choroidal melanoma.

Familial cancer history and chronic lymphocytic leukemia. A case-control study.

In a population-based case-control study carried out in the Baltimore, Maryland metropolitan area, family cancer history for 342 chronic lymphocytic leukemia cases diagnosed in 1969-1982 revealed significantly higher risks of leukemia as well as other hematolymphoproliferative neoplasms and breast cancer among their first-degree relatives compared with reported occurrence of these neoplasms in first-degree relatives of 342 matched cancer controls and 342 matched controls without cancer. Siblings of case subjects also had a significant elevation of kidney cancer compared with siblings of controls. Only one of the affected case families (and no control family) included more than one additional member with leukemia. The results suggest a genetic component for leukemia occurrence in several case families, although the majority of cases of chronic lymphocytic leukemia appeared to be sporadic. The similarity of findings between the two comparisons (cases vs. cancer controls and cases vs. controls without cancer) diminishes the likelihood of recall bias as an explanation for the observed excess risks.