Immunosuppression with Limited Toxicity: The Characteristics of Nucleoside Analogs and Anti-Lymphocyte Antibodies Used in Nonmyeloablative Hematopoietic Cell Transplantation

Abstract

The availability of two groups of pharmacologic agents, the nucleoside analogs and anti-lymphocyte antibody preparations of various specificities has enabled the development of NST. Although these agents are significantly less cytotoxic than high-dose alkylating agents and total-body irradiation (TBI), they are profoundly immunosuppressive. Opportunistic infections such as the reactivation of cytomegalovirus remain clinical obstacles when NST are performed using these agents, especially in elderly and previously immunosuppressed patients For anti-lymphocyte antibody preparations, the degree of immunosuppression produced and hence the risk of opportunistic infection varies depending upon specificity of the antibody (broad versus narrow). Allergic reactions and infusion related toxicity can occur with any antibody preparation, but the infusion of muromonab-CD3 is sometimes associated with a particularly potent cytokine-release syndrome. Although fludarabine has been the mainstay of nucleoside analog usage for NST, the other nucleoside analogs-cladribine and pentostatin are beginning to be investigated in this context.