To evaluate the role of circulating Epstein-Barr virus (EBV) DNA in lymphoma-associated hemophagocytic lymphohistiocytosis (HLH).We conducted a retrospective cohort study to explore the clinical and prognostic significance of EBV DNA in lymphoma-associated HLH. We included adult patients with combined diagnoses of lymphoma and HLH from January 2010 and November 2022 by retrieving the medical record system.A total of 281 patients with lymphoma-associated HLH were identified. Elevated whole-blood EBV DNA was observed in 54.4% (153/281) of patients, and the median copy number was significantly higher in the T/NK-cell malignancies (199,500, interquartile range, 30,000-1,390,000) than that in the B-cell non-Hodgkin lymphoma (5520, interquartile range, 1240-28,400, P < 0.001). The optimum cutoff for predicting survival was 16,100 copies/mL. Compared to the patients with EBV DNA ≤ 16,100 copies/mL, those with EBV DNA > 16,100 copies/mL were younger and had more T/NK-cell malignancies, lower levels of neutrophils and fibrinogen, and higher levels of hemoglobin, alanine aminotransferase, aspartate aminotransferase, lactic dehydrogenase, and β2-microglobulin. A higher load of EBV DNA (> 16,100 copies/mL), thrombocytopenia (< 100 × 109/L), neutropenia (< 1 × 109/L), hypofibrinogenemia (≤ 1.5 g/L), and elevated levels of creatinine (> 133 μmol/L) were independent adverse predictors of 60-day overall survival and overall survival. A prognostic index based on EBV DNA and the other four factors was established to categorize the patients into four groups with significantly different outcomes.Our study identified high EBV load as a risk factor for lymphoma-associated HLH and established a prognostic index to predict outcomes. 

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The Clinical Significance and Prognostic Role of Whole-Blood Epstein-Barr Virus DNA in Lymphoma-Associated Hemophagocytic Lymphohistiocytosis

Abstract Purpose: To evaluate the role of circulating Epstein-Barr virus (EBV) DNA in lymphoma-associated hemophagocytic lymphohistiocytosis. Methods: We retrospectively analyzed 306 adult patients with lymphoma-associated hemophagocytic lymphohistiocytosis admitted to the First Affiliated Hospital of Nanjing Medical University from August 2009 to November 2022. Results: T/NK-cell malignancies (54.3%, 166/306) were the most common subtypes, followed by B-cell non-Hodgkin lymphoma (38.2%, 117/306). Elevated whole-blood EBV DNA was observed in 55.8% (164/294) of the patients and the median number was significantly higher in the T/NK malignancies (199500, 30000-1390000) than that in the B-cell non-Hodgkin lymphoma (5520, 1240-28400, P &lt; 0.001). The optimum cutoff value for the overall survival of EBV DNA was determined as 43600 copies/mL. Compared to the patients with EBV DNA ≤ 43600 copies/mL, those with EBV DNA &gt; 43600 copies/mL were younger and had more T/NK-cell malignancies, more bone marrow infiltration, lower levels of neutrophils and fibrinogen, and higher levels of alanine aminotransferase, aspartate aminotransferase, lactic dehydrogenase, triacylglycerol, and β 2 -microglobulin. A higher load of EBV DNA (&gt; 43600 copies/mL), thrombocytopenia (&lt; 100×10 9 /L), neutropenia (&lt; 1×10 9 /L), hypofibrinogenemia (≤ 1.5 g/L), and elevated levels of creatinine (&gt; 133 μmol/L) were independent adverse predictors of overall survival. A prognostic index based on EBV DNA and the other four factors was established to categorize the patients into four groups with significantly different outcomes. Conclusion: Our study identified high EBV load as a risk factor for lymphoma-associated HLH and established a prognostic index based on EBV DNA to predict patients’ outcomes. 

/pdf/the-clinical-significance-and-prognostic-role-of-whole-blood-vdfm3k7s.pdf

The clinical significance and prognostic role of whole-blood Epstein-Barr virus DNA in lymphoma-associated hemophagocytic lymphohistiocytosis

Abstract Background Lymphoma is the most common secondary cause of hemophagocytic lymphohistiocytosis (HLH) in adults. Lymphoma‐associated HLH (LA‐HLH) in the elderly population is not rare, however, little has been reported regarding clinicopathological characteristics, prognostic factors, and outcomes of LA‐HLH in the elderly population. Methods We retrospectively analyzed a multicenter cohort of elderly patients with LA‐HLH. Clinicopathological features and treatment information were collected. The impacts of baseline characteristics and treatments on survival outcomes were analyzed. Results A total of 173 elderly patients with LA‐HLH were included. Compared with young patients, elderly patients showed different clinical and laboratory features. Regarding lymphoma subtypes, B‐cell lymphoma was more common in elderly patients (elderly 61.3% vs. young 32.3%, p &lt; 0.001) while T/NK‐cell lymphoma was more common in young patients (65.3% vs. 35.3%, p &lt; 0.001). The median survival of elderly patients with LA‐HLH was only 92 days. The prior use of HLH therapy or etoposide‐containing HLH therapy was not associated with improved overall survival. T/NK‐cell subtype, a lower platelet count (≤53 × 10 9 /L), a lower albumin level (≤32.1 g/L), a higher LDH level (&gt;1407 U/L), and a higher creatinine level (&gt;96.8 μmol/L) were independent predictors of decreased overall survival and 60‐day survival. A prognostic index was established and demonstrated to be robust in predicting the overall survival and 60‐day survival of elderly patients with LA‐HLH. Conclusions LA‐HLH in elderly patients displayed heterogeneous clinicopathological features and survival outcomes. Treatments need to be optimized to improve the outcomes of elderly patients with LA‐HLH. 

Clinicopathological characteristics, prognostic factors, and outcomes of elderly patients with lymphoma‐associated hemophagocytic lymphohistiocytosis: A multicenter analysis

Subjective To investigate clinical characteristics, treatment, and prognosis of lymphoma-associated hemophagocytic syndrome (LAHS) patients. Methods: The clinical data of patients diagnosed with LAHS from January 2010 to October 2021 in West China Hospital were retrospectively analyzed. Clinical characteristics, treatment, overall response rate (ORR), and overall survival (OS) were investigated. Univariate and multivariate analysis of potential factors were conducted. Results: Of all 94 patients included, 59 were male and 35 were female. The age at hemophagocytic lymphohistiocytosis (HLH) diagnosis was (40.5±17.3) years. Seventy-four cases were T/NK cell lymphoma; 15 were B cell lymphoma; 5 were Hodgkin lymphoma. The age at HLH diagnosis of T/NK cell LAHS patients was (37.9±16.2) years, while that of B cell LAHS patients was (55.9±14.0) years. T/NK cell LAHS patients were significantly younger than B cell LAHS patients (P<0.001). Baseline fibrinogen of T/NK cell LAHS patients was 1.34 (0.86, 2.44) g/L, while that of B cell LAHS patients was 2.20 (1.75, 4.25) g/L. T/NK cell LAHS patients showed significantly lower fibrinogen levels than B cell LAHS patients (P=0.008). Combined treatment of anti-HLH and anti-lymphoma treatment was conducted in 35 patients; anti-HLH treatment was conducted in 31 patients; anti-lymphoma treatment was conducted in 8 patients; glucocorticoid treatment was conducted in 7 patients. ORR was 49.4%, and the median OS was 61 days for overall patients. Patients who received anti-HLH treatment and turned to anti-lymphoma treatment early displayed the best ORR and OS, significantly higher than those of anti-HLH patients (69.0 vs 38.7%, P=0.019, and 192.0 vs 24.5 days, P=0.028, respectively), which were also insignificantly higher than those of anti-lymphoma patients. Extranodal NK/T-cell lymphoma or aggressive natural killer cell leukemia was the risk factor of LAHS prognosis (HR=0.113, 95%CI: 0.018-0.728, P=0.022). Conclusions: Prognosis of LAHS patients is poor. Anti-lymphoma treatment should be initiated as soon as HLH is rapidly controlled.

[Clinical characteristics and prognosis of lymphoma-associated hemophagocytic syndrome].

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[Clinical characteristics and prognosis of lymphoma-associated hemophagocytic syndrome].