Vaccine-enhanced donor lymphocyte infusion (veDLI).

Abstract

Hematopoietic stem cell or bone marrow transplantation (HSCT/BMT) is curative in many cases of hemato-logical malignancy, but the post-transplant course is often complicated by delayed immune reconstitution that predisposes to opportunistic infections and disease recurrence. Furthermore, since HLA-matched donors cannot be found for almost half of all patients that would benefit from HSCT, donors mismatched at 2-3 HLA loci are increasingly being used, which is associated with elevated rates of opportunistic infections. Donor lymphocyte infusion (DLI) is a powerful and direct approach to improve post-transplant immune function. For example, DLI using enriched antiviral cytolytic effectors (CTLs) has been shown to reconstitute cellular immunity to cytomega-lovirus (CMV) and Epstein-Barr virus (EBV) and prevent viral disease following HSCT. However, because in vitro expansion and purification of CTLs is lengthy, labor-intensive, and costly, it is rarely used clinically to prevent and treat viral infections following HSCT. Active vaccination after allogeneic transplantation to stimulate in vivo expansion of donor and/or recipient CTLs has been proposed as an alternative method to rapidly reconstitute antiviral immunity, prevent viral disease, and reduce adverse sequelae of antiviral drugs. Fortunately, recent progress has been made in developing vaccines and methodologies that are both safe and effective when administered to immunocompromised HSCT recipients.