Abstract
The outcome for patients with Epstein–Barr virus-associated hemophagocytic lymphohistiocytosis (EBV-HLH) has improved significantly since the introduction of HLH-94 type immunochemotherapy [1]; however, treatment of EBV-HLH remains difficult in patients with chronic active EBV infection (CAEBV), a form of T or natural killer (NK) cell lymphoproliferative disease (LPD). [2, 3]. Although rituximab is effective as a pre-emptive B celldirected therapy for patients with XLP1-related EBV-HLH or severe EBV-HLH, in which EBV resides within B cells, [4–7] it has been thought to be inapplicable to Asian EBVHLH patients harboring EBV-infected T or NK cells. Here, testing the hypothesis that EBV may initially reside in B cells and may continue to produce virus particles and infect T or NK cells, we employed a combination of rituximab and HLH-94 type immunochemotherapy in the initial treatment of a 64-year-old Japanese male with EBV-NKLPD-associated HLH. The patient was referred to us with fever of unknown etiology. He had been suffering from influenza A infection and had remained febrile for nearly two weeks. His past history showed that the patient had suffered an episode of fever of unknown origin five months earlier, which had been associated with high serum IgG levels; therefore, one of the referring physicians suspected collagen disease, although no definitive diagnosis was made. On admission, the patient was febrile ([39.0 C) and suffering from diarrhea. Computed tomography revealed splenomegaly, but there was no evidence of adenopathy. Blood analysis revealed the following: WBC, 3,000/lL; Hb, 10.8 g/dL; platelet count, 71,000/lL; serum aspartate aminotransferase, 225 U/L; alanine aminotransferase, 116 U/L; lactate dehydrogenase, 1,050 U/L; total bilirubin, 1.6 mg/dL, total protein, 8.2 g/dL; albumin, 2.6 g/dL; BUN, 22.7 mg/dL; creatinine, 1.36 mg/dL; CRP, 7.23 mg/dL; ferritin, 17,282 ng/mL; sIL-2R, 14,700 U/mL; b-2-microglobulin, 12.6 mg/L; total cholesterol, 78 mg/dL; IgG, 4,116 mg/dL; IgA, 337 mg/dL; IgM, 68 mg/dL; anti-nuclear antibodies (ANA), [ 2,560; anti-DNA antibodies, \ 7; plasma fibrinogen, 207 mg/dL; and D-dimer, 42.7 lg/mL. In terms of hypergammaglobulinemia, the kappa/lambda ratio was 1.2 and neither M-protein nor Bence Jones protein was positive. No specific collagen disease was identified. The clinical features and laboratory data were compatible with the diagnostic criteria for HLH. The patient was diagnosed provisionally with collagen disease-related HLH and treated with oral prednisolone (PSL 30 mg/day). However, the high fever continued and he developed severe coagulopathy associated with a marked reduction in platelet count (21,000/lL), fibrinogen (\50 mg/dL) and anti-thrombin III (AT-3; 63 %) levels; therefore, he received gabexate S. Imashuku (&) N. Kudo Division of Hematology, Takasago-seibu Hospital, 1-10-41 Nakasuji, Takasago 676-0812, Japan e-mail: shinim95@mbox.kyoto-inet.or.jp
Published Version
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