AGE, THYMOPOIESIS, AND CD4-LYMPHOCYTE REGENERATION AFTER INTENSIVE CHEMOTHERAPY( T)

Background. Inadequate reconstitution of CD4+ T lymphocytes is an impo rtant clinical problem complicating chemotherapy, human immunodeficien cy virus infection, and bone marrow transplantation, but relatively li ttle is known about how CD4+ T lymphocytes regenerate. There are two m ain possibilities: bone marrow-derived progenitors could reconstitute the lymphocyte population using a thymus-dependent pathway, or thymus- independent pathways could predominate. Previous studies have suggeste d that the CD45RA glycoprotein on CD4+ T lymphocytes is a marker for p rogeny generated by a thymus-dependent pathway. Methods. We studied 15 patients 1 to 24 years of age who had undergone intensive chemotherap y for cancer. The absolute numbers of CD4+ T lymphocytes in peripheral blood and the expression of CD45 isoforms (CD45RA and CD45RO) on thes e lymphocytes were studied serially during lymphocyte regeneration aft er the completion of therapy. Radiographic imaging of the thymus was p erformed concomitantly. Results. There was an inverse relation between the patients' ages and the CD4+ T-lymphocyte counts six months after therapy was completed (r=-0.92). The CD4+ recovery correlated quantita tively with the appearance of CD45RA+CD4+ T lymphocytes in the blood ( r=0.64). There was a higher proportion of CD45RA+CD4+ T lymphocytes in patients with thymic enlargement after chemotherapy than in patients without such enlargement (two-sided P=0.015). Conclusions. Thymus-depe ndent regeneration of CD4+ T lymphocytes occurs primarily in children, whereas even young adults have deficiencies in this pathway. Our resu lts suggest that rapid T-cell regeneration requires residual thymic fu nction in patients receiving high-dose chemotherapy.