Researchers identified characteristics associated with fever of unknown origin (FUO) that later became diagnosed as lymphoma, in addition to features associated with survival outcomes, in a new study. Results were reported in the American Journal of Translational Research.

Lymphoma is considered a common neoplastic cause of FUO. “There is, however, a scarcity of evidence revealing the variations in clinical features and prognosis of lymphoma patients who initially appear with FUO,” the researchers explained in their report.

The retrospective study included patients seen originally for FUO at Huadong Hospital of Fudan University in Shanghai, China, and who later received a lymphoma diagnosis and treatment. Patients were enrolled between January 2013 and December 2019. Patients with lymphoma, but who did not have FUO (non-FUO group), were matched to those with FUO in this study for analyses of clinical symptoms, laboratory assessments, and prognostic factors.

Continue Reading

The definition of FUO in this study included a fever of ≥38.3 degrees Celsius that persisted beyond 3 weeks, as well as an uncertain diagnosis following either 3 outpatient visits or 3 days of in-hospital investigation. Overall survival (OS) was the primary study outcome, and the secondary outcome was progression-free survival (PFS).

There were 180 evaluable patients in the FUO group, of whom 48.9% had B-cell non-Hodgkin lymphoma (B-NHL), 33.3% had T-cell non-Hodgkin lymphoma (T-NHL), 13.3% had natural killer/T-cell lymphoma (NK/T-CL), and 4.4% had Hodgkin lymphoma (HL). The non-FUO group included 329 evaluable patients, of whom 83.9% had B-NHL, 9.7% had T-NHL, 1.2% had NK/T-CL, and 5.2% had HL.

Compared with patients in the non-FUO group, subgroups of patients with FUO who had B-NHL, T-NHL, or NK/T-CL were found to have significantly higher maximum body temperatures. Some additional clinical and laboratory differences appeared to exist between patients with or without FUO across lymphoma subtypes.

OS also differed between patients in the FUO and non-FUO groups, depending on type of lymphoma. Differences in OS between groups were seen with HL (P =.0006), B-NHL (P =.007), and T-NHL (P =.013), with the FUO group appearing to show lower OS rates in these comparisons. PFS and overall response rates did not appear to significantly differ between FUO and non-FUO groups, regardless of lymphoma subtype.

A multivariate analysis revealed log10 serum ferritin to be an independent risk factor for mortality from all causes in the FUO group (HR, 9.578; 95% CI, 1.382-66.365; P =.022). Another independent risk factor for all-cause mortality in the FUO group was thrombocytopenia (HR, 1.916; 95% CI, 1.116-3.279; P =.018).

“Although lymphoma is one of the major causes of FUO, it is always a very difficult task to diagnose a patient who initially presents with FUO with lymphoma,” the researchers wrote in their report. This study had the largest sample size of any study the researchers were aware of that was aimed at identifying clinical and prognostic factors associated with lymphoma and FUO.


Wu M, Wulipan F, Ma J, et al. Clinical characteristics and prognostic factors of lymphoma patients initially presenting with fever of unknown origin. Am J Transl Res. 2022;14(4):2625-2636.

This article originally appeared on Hematology Advisor