Patterns of Infectious Morbidity in Patients with Waldenström’s Macroglobulinaemia/Lymphoplasmacytic Lymphoma: A Population-Based Study
Authors: Lund Sigrun Helga , Hultcrantz Malin , Goldin Lynn , Landgren Ola , Björkholm Magnus , Turesson Ingemar , Kristinsson Sigurdur Y 
Published: October 2019

Abstract
Background
Infections are a major cause of morbidity and mortality in patients with hematologic malignancies. However, largely due to the rarity of Waldenström’s macroglobulinemia (WM)/lymphoplasmacytic lymphoma (LPL), the literature on infectious morbidity is limited. Using population-based data from Sweden, we estimated the risk of bacterial and viral infections among 2,608 LPL/WM patients compared to 10,433 matched controls.
Patients and Methods
We identified all WM/LPL patients diagnosed 1980-2005 in the nationwide Swedish Cancer and Patient Registries, as well as a national network database including all major hematology/oncology centers; duplicate records were removed. Follow-up time was up to 2006. For each WM/LPL patient, four population-based controls (matched by age, sex, and county of residence) were identified randomly from the Swedish population database. Information on type of infection and date of infection was obtained from the Patient Registry which captures information on all individual patient-based discharge diagnosis from inpatient (since 1964) and outpatient care (since 2000). Through linkage to the nationwide Cause of Death Registry, we identified dates of death for WM/LPL patients and controls. Cox proportional hazard models were used to estimate the overall risk of infections. Models were adjusted for sex, age, and calendar period. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated for individual infections.
Results
Overall, WM/LPL patients had a 3.4-fold (95% CI=3.1-3.6) elevated risk of developing any infection than controls (Figure). Compared to controls, the risk of developing bacterial and viral infections was 3.2-fold (95%; CI=2.9-3.5) and 6.0-fold (95% CI=4.9-7.3) higher, respectively. More specifically, WM/LPL patients had an increased risk (p<0.05) of the following types of bacterial infections: septicaemia (HR=9.3; 95% CI 3.7-23.5), endocarditis (HR=5.0; 95% CI 2.5-10.0), pneumonia (HR=3.8; 95% CI 3.4-4.2), meningitis (HR=3.4; 95% CI 1.1-10.3), cellulitis (HR=2.6; 95% CI 2.0-3.4), osteomyelitis (HR=1.9; 95% CI 1.01-3.6), and pyelonephritis (HR=1.6; 95% CI 1.2-2.4). Regarding viral infections, WM/LPL patients had an increased risk of herpes zoster (HR=9.2; 95% CI 6.7-12.6) and influenza (HR=2.3; 95% CI 1.5-3.5). The risk of infections was highest during the first year after diagnosis. Interestingly, WM/LPL patients diagnosed in the more recent calendar periods had significantly higher risk of infections (Figure). Compared to WM/LPL patients diagnosed in 1980-1989, patients diagnosed in 1990-1999 and 2000-2004 had a 1.5-fold (95% CI=1.3-1.6) and 1.8-fold (95% CI=1.6-2.1) increased risk of any infection, respectively. The same patterns were observed when bacterial infections were analyzed separately. In analysis focusing on viral infections; there was only a significant increased risk during the most recent calendar period (p=0.027). Females had a significantly lower risk of infections compared to males (p<0.001). Increasing age was significantly associated with a higher risk of infections (p<0.001).
Discussion
In this large population-based study including over 2,600 WM/LPL patients and 10,000 matched controls, we found that bacterial and viral infections represent a major threat to WM/LPL patients. This was particularly true during the first years following diagnosis. Importantly, the risk of infections increased in more recent years. The effects on infectious complications due to novel drugs in the treatment of WM/LPL need to be better defined and trials on prophylactic measures are needed.
Figure 1 Figure 1.

Disclosures
No relevant conflicts of interest to declare.