Possible Eradication of Minimal Residual Disease in Acute Leukemia.

The complete remission (CR) rate in acute leukemia (AL) has been improved due to progressive chemotherapy. However, relapse frequently occurs as minimal residual disease (MRD). To eradicate MRD, immunotherapy using autologous cytotoxic T-lymphocytes has been available. Leukemia cells (LC) of the patients were stored frozen before chemotherapy. Furthermore, after achieving CR, an EBV-transformed lymphoblastoid B-cell line (LCL) was established in each case. To induce Cytotoxic T-lymphocytes (CTL), co-culture system was carried out in two types. One is co-culture of peripheral blood mononuclear cells (PBMCs) and original leukemia cells (LC), the other is co-culture of PBMCs and the patient’s own LCL. After co-culture for 5 days, cytotoxic activity was examined by FACS with PKH-26 staining. Interestingly, cytotoxicity against not only autologous LC but the patient’s own LCL was observed in almost cases. This phenomenon is called cross-killing. Moreover, regulatory T-cells (Treg) were detected in the effecter phase determined with FACS (CD4+ CD25+) and FOXP3 mRNA by RT-PCR. Enhanced cytotoxicity was observed in inverse relation to a low proportion of Treg. These results suggested that more cytotoxicity may be induced by deletion of the Treg population. In conclusion, cell therapy as an immunotherapy should be useful tool to improve the prognosis, and if stocked LC is not available, CTL activity must be induced by co-culture with the patient’s own LCL.