Clinical effects of infusing anti-Epstein-Barr virus (EBV)-specific cytotoxic T-lymphocytes into patients with severe chronic active EBV infection.
Immune cell therapy with autologous Epstein-Barr virus (EBV)-specific cytotoxic T-lymphocytes (CTLs) or lymphokine-activated killer (LAK) cells was performed in 2 adults with severe chronic active EBV infection (SCAEBV). The patient in case 1, who had complications of pancytopenia, high fever, and massive splenomegaly, was treated with 13 doses of LAK cell infusion followed by 4 doses of autologous CTL infusion. The patient in case 2, who had liver dysfunction due to natural killer cell-type infection, was treated with 4 doses of autologous CTL infusion. In case 1, the LAK cell infusions were effective in lowering the viral load and improving several biochemical parameters (lactate dehydrogenase, soluble interleukin 2 receptor) and resulted in complete amelioration of the high fever. Subsequent infusions of autologous CTLs reduced the viral load only temporarily and were accompanied by an increase in frequency of EBV-specific T-cells in the blood. However, the patient's main problem of pancytopenia was not resolved. In case 2, infusion of autologous CTLs did not improve the patient's hepatic dysfunction or viral load but caused a significant increase in autoantibody levels. Thus the effect of auto-CTL treatment was limited or deteriorative in SCAEBV patients.
Hagihara
Masao
M
Department of Hematology and Oncology, Tokai University School of Medicine, Isehara, Kanagawa, Japan. masaoha@is.icc.u-tokai.ac.jp
Tsuchiya
Takahide
T
Hyodo
Osamu
O
Ueda
Yoko
Y
Tazume
Kei
K
Masui
Aya
A
Kanemura
Ayako
A
Yoshiba
Fumiaki
F
Takashimizu
Shinji
S
Matzusaki
Shohei
S
Kato
Shunichi
S
Hotta
Tomomitsu
T
D019264:Adoptive Transfer / Q000379:methods*; D000328:Adult; D002908:Chronic Disease; D020031:Epstein-Barr Virus Infections / Q000628:therapy*; D005260:Female; D004854:Herpesvirus 4, Human / Q000276:immunology*; D006801:Humans; D015979:Killer Cells, Lymphokine-Activated / Q000276:immunology / Q000637:transplantation; D008297:Male; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology / Q000637:transplantation*; D014182:Transplantation, Autologous; D016896:Treatment Outcome