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T-Cell Immunodeficiency Following Cytotoxic Antineoplastic Therapy: A Review

Pediatric Oncology Branch, National Cancer Institute, Bethesda, Maryland, USA

Correspondence: Crystal L. Mackall, M.D., Pediatric Oncology Branch, National Cancer Institute, Bldg. 10, Rm. 13N240, 10 Center Dr., MSC 1928 Bethesda, Maryland 20892, USA. Telephone: 301-402-5940; Fax: 301-402-0575; e-mail: cm35c{at}nih.gov

Although cancer itself is immunosuppressive, cytotoxic antineoplastic therapy is the primary contributor to the clinical immunodeficiency observed in cancer patients. The immunodeficiency induced by cytotoxic antineoplastic therapy is primarily related to T-cell depletion, with CD4 depletion generally more severe than CD8 depletion. Myeloablative therapy, dose-intensive alkylating agents, purine nucleoside analogs, and corticosteroids substantially increase the risk of therapy-induced immunosuppression. Restoration of T-cell populations following cytotoxic antineoplastic therapy is a complex process. Efficient recovery of CD4⁺ T cell populations requires thymic-dependent pathways which undergo an age-dependent decline resulting in prolonged CD4⁺ T-cell depletion in adults following T-cell-depleting therapy. Total CD8⁺ T-cell numbers recover in both children and adults relatively quickly post-therapy; however, CD8⁺ subset disruptions often remain for a prolonged period. The clinical management of patients with therapy-induced T-cell depletion involves the maintenance of a high index of suspicion for opportunistic pathogens, irradiation of blood products, prophylaxis for viral infections, and reimmunization in selected clinical circumstances. Future research avenues include efforts to rapidly rebuild immunity following cytotoxic antineoplastic therapy so that immune-based therapies may be utilized immediately following cytotoxic therapy to target minimal residual neoplastic disease.

Key Words. Immunodeficiency • Thymus • T cells • Immune reconstitution

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