Three midwestern American adults with a rare and aggressive cancer caused by a virus they had never heard of are finding new hope in being treated at the OSUCCC – James. One is being screened and two have already enrolled on an international phase II clinical trial that recently opened at the OSUCCC – James for patients with relapsed or refractory (treatment-resistant) extranodal NK-T cell lymphoma (ENKTL), a form of lymphoma that is universally associated with the Epstein-Barr virus (EBV) and can now be treated by attacking that virus. EBV infects more than 90 percent of the population worldwide but remains dormant in most people throughout their lifetime. Exposure to EBV is most often asymptomatic, but it leads to infectious mononucleosis in about 20 percent of cases. Much more rarely, it leads to ENKTL. “ENKTL affects no more than 300 to 400 new patients every year in the United States, and many doctors are not familiar with it,” says Pierluigi Porcu, MD, an associate professor in the Division of Hematology at Ohio State and a lymphoma researcher at the OSUCCC – James. “Some cases may go undiagnosed, and late diagnosis is the rule.” Porcu says almost all patients with ENKTL share very similar medical stories. They often have long bouts of cold-like symptoms that do not improve with the use of saline sprays, decongestants and antibiotics. They are often referred to ear, nose and throat specialists, and some have CAT scans that reveal severe inflammation. Then come biopsies that may return inconclusive, often followed by prescriptions for strong antifungal antibiotics on suspicion of invasive fungal infection of the sinuses. When this treatment fails, the patients may receive additional biopsies that ultimately lead to their diagnoses of ENKTL. Porcu says earlier diagnoses may be made if patients with these persistent symptoms are tested for EBV during their initial biopsy. “But since many doctors have never seen ENKTL, generally the EBV test is done only after the biopsy report is sent to a National Cancer Institute (NCI)-designated Comprehensive Cancer Center such as the OSUCCC – James,” he adds. Treatment for ENKTL typically consists of intensive chemotherapy with a combination of drugs, followed by high-dose radiation. “However,” Porcu says, “many patients relapse, and because there are no good rescue therapies, death from progressive disease is unfortunately common.”   But the three aforementioned patients with ENKTL were able to pursue a clinical trial at the OSUCCC – James called Cellular Immunotherapy Treatment Antigen Directed for EBV Lymphoma (CITADEL), a study based on a treatment strategy that leverages each patient’s immune system to fight the EBV-infected lymphoma. “Blood cells from each patient are exposed to a layer of EBV-infected cells, stimulated and expanded until, about six weeks later, an army of immune T-cells trained to fight EBV is available for use,” Porcu explains. “The EBV-specific immune T-cells are then infused into the patient over six months. In a previous clinical trial, this treatment was found to be safe, and physicians observed sustained complete responses in more than 80 percent of patients with a variety of EBV-positive lymphomas. “Thus, we have great hope that this new treatment will save the lives of many patients with ENKTL who have no other good options.”