Thymus-dependent regeneration of CD4+ T lymphocytes occurs primarily in children, whereas even young adults have deficiencies in this pathway. Our results suggest that rapid T-cell regeneration requires residual thymic function in patients receiving high-dose chemotherapy.

Rapid recovery of CD4 " T cells after intensive chemotherapy recovery among patients with or without thymic enlargeis limited by an age-dependent decline in thymopoiesis. Here ment, whereas CD4 " recovery was enhanced in patients we sought to determine whether similar limitations exist with thymic enlargement after chemotherapy (P Ú .01). for CD8 " T-cell regeneration. After intensive chemotherapy, Therefore thymic-independent pathways of T-cell regenera-CD8 " T cells had a faster effective doubling time than CD4 " tion appear to rapidly regenerate substantial numbers of T cells (median, 12.6 v 28.2 days, P Ú .05). Accordingly, at 3 CD8 " , but not CD4 " T cells, resulting in prolonged T-cell submonths posttherapy, mean CD8 " T-cell number had returned set imbalance after T-cell depletion. These inherent distincto baseline, whereas mean CD4 " T-cell number was only tions between CD4 " v CD8 " T-cell regeneration may have 35% of pretherapy values (P Ú .05). These differences were significant implications for immunotherapeutic strategies primarily due to very rapid expansion of CD8 " CD57 " and undertaken to eradicate minimal residual neoplastic disease CD8 " CD28 Ï subsets. At 3 months posttherapy, there was no after cytoreductive chemotherapy. relationship between age and CD8 " T-cell number (R ! Ï.02), This is a US government work. There are no restrictions on whereas CD4 " T-cell number was inversely related to age (R its use. ! Ï.66) and there were no discernible differences in CD8 " From the Pediatric Branch, Experimental Immunology Branch, versus thymic-independent pathways of regeneration. Sevcould be due to inherent biologic differences in CD4 / versus Health, Bethesda; and the Henry M. Jackson Foundation for the CD8 / regenerative pathways, unique clinical circumstances plausible explanations. For example, because CD8 / T-cell Address reprint requests to Crystal L. Mackall, MD, Bldg 10, Rmnumbers are highest in patients with graft-versus-host dis- 13N240, 10 Center Dr, MSC 1928, Bethesda MD 20892-1928 ease (GVHD) 17,18 and/or cytomegalovirus infection, 19 the rel-The publication costs of this article were defrayed in part by page atively rapid CD8 / regeneration observed may be due to charge payment. This article must therefore be hereby marked high level antigenic stimulation and unique to the post-BMT ''advertisement'' in accordance with 18 U.S.C. section 1734 solely to setting. In addition, a lack of quantification of the inocula indicate this fact. of mature T cells administered within the bone marrow graftThis is a US government work. There are no restrictions on its use.

ICRF-187 reduces the risk of developing short-term subclinical cardiotoxicity in pediatric sarcoma patients who receive up to 410 mg/m2 of doxorubicin. Response rates to chemotherapy, event-free and overall survival, and noncardiac toxicities appear to be unaffected by the use of ICRF-187. Additional clinical trials with larger numbers of patients are needed to determine if the short-term cardioprotection afforded by ICRF-187 will reduce the incidence of late cardiac complications in long-term survivors of childhood cancer.