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Review
. 2024 Mar 18;6(1):116-127.
doi: 10.46989/001c.94954. eCollection 2024.

A Retrospective Review of Secondary Hemophagocytic Lymphohistiocytosis (HLH) and Dengue-associated HLH from a Teaching Hospital in Singapore

Allison C Y Tso  1 , Sanchalika Acharyya  2 , Sing Zern Fong  1 , Lian K Lee  1 , Sampath V Sreekanth  1 , Bingwen E Fan  1 , Seok W S Chan  3 , Kiat H Ong  1
Affiliations
Review

A Retrospective Review of Secondary Hemophagocytic Lymphohistiocytosis (HLH) and Dengue-associated HLH from a Teaching Hospital in Singapore

Allison C Y Tso et al. Clin Hematol Int. .

Abstract

Real-world data on the outcome of Asian patients with secondary hemophagocytic lymphohistiocytosis (HLH), especially on dengue-associated HLH, are limited to small case series. This is a retrospective records review of adult patients with secondary HLH between 2015 and 2020. Thirty-two adult patients were followed up for a median of 6.6 months (range 0.1 - 75 months). 15 had underlying lymphomas, and 12 had viral infections. Hemophagocytosis was seen in 28 of 29 patients with a bone marrow biopsy. 100% and 76.5% of patients with and without an underlying malignancy required HLH-directed therapy and blood product transfusion. 12 of 15 patients with lymphomas were treated with additional chemotherapy. Patients with malignancy-associated HLH had poorer survival than non-malignancy-associated HLH (median overall survival (OS) 1.5 months versus not reached, p-value 0.003). The 1-year survival rates of patients with malignancy-associated HLH, HLH with unknown etiologies, and infection-associated HLH were 0.133 (95% CI: 0.036 - 0.484), 0.400 (95% CI: 0.137 - 1.000) and 0.833 (95% CI: 0.647 - 1.000), respectively. Malignancy significantly increased the risk of death compared to infection-associated HLH (HR 9.37, p-value 0.003). Eight patients were diagnosed with dengue-associated HLH with a median HSCORE of 240 (98-99% probability of HLH). Their mean ferritin was 34,740 ng/mL. Three patients required blood product transfusion, 5 required corticosteroids and/or etoposide, with a median duration of treatment of 31 days. Their overall survival rate was 87.5%. Our study highlights the stark contrast in the survival of secondary HLH patients with and without an underlying malignancy. We also present one of the world's most extensive case series of dengue-associated HLH.

Keywords: dengue; hemophagocytic lymphohistiocytosis; lymphoma; viral infections.

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Conflict of interest statement

All authors certify that they have no affiliations with or involvement in any organization or entity with any financial or non-financial interest in the subject matter or materials discussed in this manuscript. No funding was received to conduct this study.

Figures

Figure 1.
Figure 1.. Distribution of indications for starting HLH treatment, apart from HLH in marrow and HLH parameters
Figure 2.
Figure 2.. Kaplan–Meier curve for overall survival of patients with malignancy versus non-malignancy associated hemophagocytic lymphohistiocytosis
Figure 3.
Figure 3.. Kaplan–Meier curve for overall survival of patients with hemophagocytic lymphohistiocytosis; a comparison of three subtypes
Figure 4.
Figure 4.. Distribution of cause of death by three underlying etiologies of HLH
See this image and copyright information in PMC

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