Longitudinal observation and outcome of nonfamilial childhood haemophagocytic syndrome receiving etoposide‐containing regimens

Abstract

Summary. The long-term outcome of 22 children treated with etoposide-containing regimens for haemophagocytic syndrome (HS) were longitudinally studied; none of them had a family history of the disease. All patients received etoposide-containing (150 mg/m 2 /d) regimens, combined, in 16 cases, with intravenous immunoglobulin (IVIG) and prednisolone. Complete remission (CR) was achieved in 12 patients, partial remission in seven, and early mortality occurred in three. Of the 12 CR patients, only four remain alive and disease-free, with a median follow-up of 47·4 months; one CR patient died due to infection and the remaining seven had relapsed diseases. Three patients with a partial response or with relapsed disease progressed to T-cell lymphoma, characterized, in the two cases tested, by clonal chromosomal abnormalities. Epstein-Barr virus (EBV) infection was implicated in disease pathogenesis in 15/22 patients. The overall survival was 45·5%, 40·9% and 40·9% at 1, 3 and 5 years, respectively, and disease-free survival for CR patients at these same times was 45·5%, 36·4% and 36·4%. The etoposide-containing regimen would appear to be an effective initial therapeutic option for childhood HS. However, in view of the frequency of partial remissions and relapsed disease, a more intensive chemotherapy or bone marrow transplantation should be applied. The progression to EBV-containing T-cell lymphoma in three patients is consistent with the previous observation that EBV-associated HS is a potentially malignant disease.

Profiling of EBV-Encoded microRNAs in EBV-Associated Hemophagocytic Lymphohistiocytosis

“…It is well known that EBV also displays latency II in EBV-associated T-cell lymphomas (Cohen 2000;Forte and Luftig 2011). EBV-HLH is likely to relapse or progress to T-cell lymphoma over months to years (Su et al 1993;Yao et al 1994;Chen et al 1998). The same latency type may be related to the mechanism of disease progression from EBV-HLH to T-cell lymphoma.…”

Epstein-Barr virus LMP1 inhibits the expression of SAP gene and upregulates Th1 cytokines in the pathogenesis of hemophagocytic syndrome

“…Three patients responded to the therapy using a protocol of intravenous immunoglobulin (IVIG)/VP-16, 38 2 had chronic active diseases, and 2 had rapidly progressive diseases.…”

“…37,38 Tissues or freshly frozen cells were available for DNA and RNA extraction in 7 cases, including lymph nodes in 2 cases, spleen in 1 case, skin in 1 case, and bone marrow in 3 cases. As controls, 10 specimens of reactive lymphoid hyperplasia (5 cases), IM (2 cases), and nasal type NK/T-cell lymphoma (3 cases) were included.…”

Epstein-Barr Virus (EBV) Latent Membrane Protein-1 Down-Regulates Tumor Necrosis Factor-α (TNF-α) Receptor-1 and Confers Resistance to TNF-α-Induced Apoptosis in T Cells

“…7,29,30 These findings suggested to us that the EBV-infected T cells may survive or even proliferate in the cytokine milieu of HPS, in which TNF-␣ is presumed to be the culprit cytokine. 8 Consistent with previous studies, 26 we demonstrated here that EBV LMP-1 could up-regulate TNF-␣ via a TRAFs/NF-B pathway in EBV-infected T cells.…”

“…26 Although current therapy has been successfully used to control HPS in patients, 27,28 a substantial percentage of patients who received initial treatment may develop relapsing disease or even progress to T-cell lymphoma. 29,30 Therefore, it is reasonable to speculate whether EBV-infected T cells are less sensitive to the cytokinemediated cytotoxicity than the surrounding uninfected or bystander cells and hence survive or proliferate in the cytokine milieu of HPS. In this study, we performed a series of experiments to test this hypothesis.…”