Immunologic reconstitution after allogeneic stem cell transplant.

Abstract

Patients submitted to allogeneic stem cell transplantation have a prolonged immunodeficiency, extending beyond one year post-transplant. The immune reconstitution after an allogeneic stem cell transplant is dependent upon several factors, such as the age of the recipient, the degree of in vivo or in vitro T-cell depletion, the emergence and eventual treatment of graft versus host disease. While neutrophils and NK cells recover normally within 2 months of transplant, the reconstitution of B- and T-cell immunity is significantly slower. In fact, it is impossible to dissociate the emergence of new B-lymphocytes from thymopoiesis, which appears to be determinant for the normal reconstitution of acquired immunity post-transplant. The serial analysis of T cell counts and its subsets, as well as T-cell function and, more recently, of T-cell receptor excision circles, show a delay in T-cell reconstitution in adult patients, patients with extensive chronic graft versus host disease and in the first 9 months post-transplant in recipients of T-cell depleted grafts. The incidence of opportunistic infections is higher in this population. Therefore, with the aim of reducing post-transplant mortality, the development of new strategies for the acceleration of immune reconstitution is crucial. One possibility is the use of adoptive cellular immunotherapy with donor leukocytes in order to boost the incipient donor's immune system in the receptor. Preliminary studies in animal models also suggest that interleukin-7 and keratinocyte growth factor improve thymopoiesis, thereby stimulating the immune reconstitution post-transplant.