Rapid development of ganciclovir-resistant cytomegalovirus infection in children after allogeneic stem cell transplantation in the early phase of immune cell recovery.
As recently reported, children having T cell-depleted peripheral blood stem cell transplantation (PBSCT) might be at increased risk for the development of drug resistance. To investigate if delayed immune recovery was a potential risk factor, the recovery of the CD3(+), CD4(+), CD8(+) and CD19(+) cells was related retrospectively to genotypic detected resistance development in three pediatric patients with ganciclovir (GCV)-resistant human cytomegalovirus (HCMV)-infection out of 79 receiving allogeneic PBSCT. Selected control groups consisted of HCMV-seronegative patients without any infection (A, n = 8), asymptomatic infected patients with viral leuko- and plasmaDNAemia (B, n = 4) and patients with HCMV-disease (pneumonia) (C, n = 3). Patient No. 1 with very early resistance development exhibited a rapid immune recovery with higher T cell counts than in group A. Immune recovery of patient No. 2 was delayed, as also observed in groups B and C. Patient No. 3 showed an immune recovery comparable to group A. Resistance developed before (No. 2) or during (Nos 1 and 3) the recovery of the relevant CD3(+), CD4(+), CD8(+) lymphocytes. GCV-resistance development did not necessarily coincide with delayed immune recovery, but appeared in all three cases in the early phase of immune recovery (range: day +44 to day +95). Therefore, children seem to be at special risk for resistance development in the early phase after transplantation before immune cells have recovered. These results suggest that GCV treatment of an HCMV infection in the early posttransplant phase of children after T cell-depleted PBSCT/BMT should promote more stringent resistance screening.
D015703:Antigens, CD / Q000032:analysis; D016022:Case-Control Studies; D002648:Child; D003586:Cytomegalovirus Infections / Q000188:drug therapy / Q000209:etiology*; D024882:Drug Resistance, Viral / Q000235:genetics*; D015774:Ganciclovir / Q000494:pharmacology*; D006085:Graft Survival; D006801:Humans; D007107:Immune System / Q000166:cytology* / Q000254:growth & development; D008212:Lymphocyte Depletion / Q000009:adverse effects; D009154:Mutation; D036102:Peripheral Blood Stem Cell Transplantation / Q000009:adverse effects*; D010770:Phosphotransferases / Q000235:genetics; D012189:Retrospective Studies; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology; D014184:Transplantation, Homologous
D015703:Antigens, CD; D010770:Phosphotransferases; D015774:Ganciclovir