Treatment of EBV, CMV, and Adenovirus Infections in Primary Immunodeficiency Disorders With Viral-specific Cytotoxic T-Lymphocytes
PIDD represent an expanding group of genetic disorders that compromise immunity against bacteria, viruses, and fungi. The most severe forms of PIDD cause profound susceptibility to opportunistic infections due to impaired or absent T-cell immunity. These diseases can be rapidly fatal unless treated via hematopoietic stem cell transplantation (HSCT). Chronic viral illnesses are a common presenting feature of many of these disorders, and studies have shown that survival of HSCT is profoundly impacted by the patient's pre-transplant disease status. Primary infections with viruses such as cytomegalovirus (CMV) and Epstein-Barr virus (EBV) are common, and respiratory viruses such as adenovirus also frequently cause infection. In patients with severe combined immunodeficiency (SCID), a prior study identified these viruses as the most common causes of mortality in the immediate period following HSCT. Though some forms of PIDD are amenable to HSCT without requiring conditioning chemotherapy, many forms require a variable degree of pre-conditioning to ensure that stable engraftment of the donor cells is achieved. The administration of cytotoxic chemotherapy used in the conditioning regimens can however increase the risk for regimen related toxicity and for some patients (especially those with active viral infections) this risk is particularly high, leading to high treatment related mortality rates. For these reasons, many such patients are not even considered candidates for HSCT or are delayed getting to HSCT and ultimately succumb to infection before they can receive the transplant. The primary objective of this study is to determine the safety of administering third-party multivirus-specific cytotoxic T lymphocytes (mCTL) from adult CMV seropositive donors to treat refractory viral infections in patients with primary immunodeficiency disorders (PIDD) prior to hematopoietic stem cell transplantation (HSCT).