TREATMENT OF FULMINANT HEMOPHAGOCYTIC LYMPHOHISTIOCYTOSIS WITH COMBINED ADMINISTRATION OF OKT-3 AND ETOPOSIDE

We reported a case of life-threatening hemophagocytic lymphohistiocyto sis (HLH) treated with etoposide and anti-CD3 monoclonal antibody (OKT -3). A 3-year-old boy with fulminant HLH, characterized by CD3(+) CD56 (-) atypical lymphocytosis and hemophagocytosis in peripheral blood an d bone marrow, whose disease was refractory to conventional therapies including glucocorticoids, cyclosporine A, a small dose of etoposide a nd plasma exchange, was treated with a combination therapy of OKT-3 an d etoposide. Analysis of mononuclear cells for clonality was performed . DNA derived from Epstein-Barr virus, herpes virus-6 and cytomegalovi rus was also detected in mononuclear cells from the patient. The plasm a cytokine levels were serially evaluated. By DNA analyses, monoclonal proliferation of T cells and a monoclonal population of cells contain ing the Epstein-Barr virus genome was demonstrated. With administratio n of two doses of 5 mg/m(2) of OKT-3 combined with 100 mg/m(2) of etop oside, atypical lymphocytes rapidly disappeared, and hematopoietic rec onstitution was seen with disappearance of activated macrophages in th e bone marrow 7 days after OKT-3 administration. Consistent overproduc tion of IL-10 through the clinical course was observed. Combined admin istration of OKT-3 with etoposide was effective in this patient. It se ems appropriate to try this therapy for fulminant HLH refractory to co nventional therapies.