Examples of CMV-specific immune reconstitution in individual patients.
(A) In patient 1, CMV-specific CTL were detected on day 33 but were at low levels during prolonged treatment with prednisolone. After an episode of CMV reactivation on day 82 and a short course of ganciclovir therapy, the number of CMV-specific CTL increased to a high level. A CTL assay done 4 months before transplantation had shown that CTL numbers were considerably lower than those observed after recovery from reactivation. (B) Patient 5 had early and sustained immune reconstitution, but the percentage of tetramer-binding CTL fell from 9.8% of CD8+ T cells to 5.7% after the introduction of prednisolone for control of GVHD. A similar reduction in CTL numbers was also observed (data not shown). (C) Patient 10 received stem cells from an unrelated donor, and no CTL were detectable until day 116. After a second episode of CMV reactivation on day 126, CTL increased to levels of 70 × 105/L. A course of prednisolone therapy suppressed CTL numbers and, following recovery, CTL were virtually eliminated after unsuccessful donor leukocyte infusions and chemotherapy for cytogenetic relapse of chronic myeloid leukemia. Introduction of the tyrosine kinase inhibitor STI571 was associated with recovery of CTL numbers. (D) Patient 12 also received stem cells from an unrelated donor. After an early period of CMV reactivation, the patient was given a prolonged course of ganciclovir therapy. CMV-specific CTL were detected only after discontinuation of the drug. P indicates prednisolone; GCV, ganciclovir; vertical lines with CMV Ag+, episode of CMV reactivation; mito, mitoxantrone; and STI571, tyrosine kinase inhibitor. The x-axis represents days after transplantation. All drug doses are in milligrams. Cell numbers on the y-axis are × 105/L cells.
