This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Reactivation of EBV after BMT from a mismatched family member or matched unrelated donor frequently leads to lymphoproliferation that is often fatal. Since 1993, we have generated donor-derived EBV-specific CTLs and administered them as prophylaxis and treatment for this complication. 58 patients received CTLs prophylactically and nine of the patients on the prophylaxis study had evidence of incipient EBV lymphoma prior to CTL infusion. In 6 patients the abnormalities resolved without sequelae after CTL infusion. The other 3 developed local inflammation during a therapeutic response with one developing adenoid enlargement with necrosis, one developing fever and a LLL pulmonary infiltrate and the third a transient elevation in transaminases. None of the patients in the prophylaxis study developed EBV lymphoma compared to an incidence of 11.5% in patients not receiving prophylaxis. Six patients not enrolled on the prophylaxis study received CTLs as treatment for EBV lymphoproliferative disease. One patient died with progressive disease because the tumor virus had deleted viral epitopes that dominated the donor immune response to EBV. This illustrates one anticipated problem of immunotherapy; that the tumor will mutate to avoid the immune response. The other three patients who were treated for clinically evident EBV-LPD attained prolonged remission after CTL infusion and in situ hybridization and semiquantitative PCR showed that the gene marked CTL had selectively accumulated at disease sites. Polyclonal donor-derived EBV-specific T-cell lines can therefore be used safely to prevent EBV-related lymphoma post allo-BMT with long-term persistence of adoptively transferred cells.
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