Respiratory tract infections in the pathway to multiple myeloma: a population-based study in Scandinavia.

Encounter with infectious antigens has been proposed to initiate the cascade of events associated with progression from premalignancy (monoclonal gammopathy of undetermined significance, MGUS) to multiple myeloma (MM). We conducted a population-based case-control study to evaluate risk of developing MM associated with a personal history of various respiratory tracts infections occurring >1 year prior to MM. Inpatient (1977-1997) and outpatient (1994-1997) diagnoses were obtained for all MM patients (n=4,476) diagnosed in Denmark (1977-1997) and 16,727 matched controls. A personal history of pneumonia was associated with a 1.6-fold (95%CI 1.3-2.0) increased risk of MM; the elevated risk was restricted to 1-4.99 years prior to the diagnosis of MM (OR=1.7,95%CI 1.3-2.2). Individuals with two and three or more previous episodes of pneumonia had a 1.7-fold (95%CI 1.0-3.0; p=0.05) and a 1.5-fold (95%CI 0.6-3.9) elevated MM risk, respectively. Pneumonia could be a trigger to the development of MM or a manifestation of immune disturbances in late-stage MGUS.

Survival patterns among lymphoma patients with a family history of lymphoma.

PURPOSE: Genetic factors are important in the etiology and pathogenesis of chronic lymphocytic leukemia (CLL), Hodgkin's lymphoma (HL), and non-Hodgkin's lymphoma (NHL). Only a few small studies have assessed clinical characteristics and prognosis for familial patients, with inconsistent findings. METHODS: Using population-based registries from Sweden and Denmark, 7,749 patients with CLL, 7,476 patients with HL, and 25,801 patients with NHL with linkable first-degree relatives were identified. Kaplan-Meier curves were constructed to compare survival in patients with lymphoma with and without a family history of lymphoma. The risk of dying was assessed using adjusted Cox proportional hazard models. RESULTS: We found 85 patients with CLL (1.10%), 95 patients with HL (1.28%), and 206 patients with NHL (0.80%) with a family history of any lymphoma. Five-year mortality was similar for patients with CLL (hazard ratio [HR], 1.28; 95% CI, 0.95 to 1.72), HL (HR, 0.78; 95% CI, 0.49 to 1.25), and NHL (HR, 0.91; 95% CI, 0.74 to 1.12) versus without a family history of any lymphoma. Mortality was also similar for patients with versus without a family history of the same lymphoma. T-cell/anaplastic lymphoma patients with a family history of NHL had poorer outcome 5-years after diagnosis (HR, 5.38; 95% CI, 1.65 to 17.52). Results were similar for 10 years of follow-up. CONCLUSION: With the exception of T-cell/anaplastic lymphoma, survival patterns for patients with CLL, HL, and NHL with a family history of lymphoma were similar to those for sporadic patients, suggesting that most familial lymphomas do not have an altered clinical course. Our findings provide no evidence to modify therapeutic strategies for patients with CLL, HL, or NHL based solely on family history.

Respiratory tract infections and subsequent risk of chronic lymphocytic leukemia.

Recent evidence suggests that chronic lymphocytic leukemia (CLL) might occur following a response to an infectious agent. We conducted a population-based study including 4249 CLL patients diagnosed in Denmark from 1977 to 1997 and 15 690 frequency-matched controls to quantify risk of CLL following various airway infections. Through data linkage we gathered information on hospital inpatient/outpatient discharges that listed infections present at least 1 year prior to CLL. Using logistic regression, we calculated odds ratios (ORs) and 95% confidence intervals (CIs). Personal history of pneumonia was associated with significantly increased CLL risk (OR = 1.4; 1.2-1.8); risk was restricted to 1 to 4.99 years prior to CLL diagnosis (OR = 1.6; 1.2-2.0). Individuals with 3 or more prior pneumonia events had a significant 2.5-fold (1.1-5.6) elevated CLL risk, and risk increased with the number of pneumonia episodes (P(trend) < .001). None of 9 other respiratory-tract infections was significantly associated with CLL risk. Pneumonia might be a potential CLL trigger or it could represent premalignant immune disruption preceding CLL.