Abstract
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.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 12 print issues and online access
$259.00 per year
only $21.58 per issue
Rent or buy this article
Prices vary by article type
from$1.95
to$39.95
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Drew WL . Ganciclovir resistance: a matter of time and titre Lancet 2000 356: 609 610
Limaye AP, Corey L, Koelle DM et al. Emergence of ganciclovir-resistant cytomegalovirus disease among recipients of solid-organ transplants Lancet 2000 356: 645 649
Erice A . Resistance of human cytomegalovirus to antiviral drugs Clin Microbiol Rev 1999 12: 286 297
Gilbert C, Roy J, Belanger R . Lack of emergence of cytomegalovirus UL97 mutations conferring ganciclovir (GCV) resistance following preemptive GCV therapy in allogeneic stem cell transplant recipients Antimicrob Agents Chemother 2001 45: 3669 3671
Prix L, Hamprecht K, Holzhüter B et al. Comprehensive restriction analysis of the UL97 region allows early detection of ganciclovir-resistant human cytomegalovirus in an immunocompromised child J Infect Dis 1999 180: 491 495
Eckle T, Prix L, Jahn G et al. Drug-resistant human cytomegalovirus infection in children after allogeneic stem cell transplantation may have different clinical outcomes Blood 2000 96: 3286 3289
Wolf DG, Yaniv I, Honigman A et al. Early emergence of ganciclovir-resistant human cytomegalovirus strains in children with primary combined immunodeficiency J Infect Dis 1998 178: 535 538
Hamprecht K, Steinmassl M, Einsele H, Jahn G . Discordant detection of human cytomegalovirus DNA from peripheral blood mononuclear cells, granulocytes and plasma: correlation to viremia and HCMV infection J Clin Virol 1998 11: 125 136
Hamprecht K, Mikeler E, Jahn G . Semi-quantitative detection of cytomegalovirus DNA from native serum and plasma by nested PCR: influence of DNA extraction procedures J Virol Meth 1997 69: 125 135
Prix L, Maierl J, Jahn G, Hamprecht K . A simplified assay for screening of drug resistance of cell-associated cytomegalovirus strains J Clin Virol 1998 11: 29 37
Handgretinger R, Schumm M, Lang P et al. Transplantation of megadoses of purified haploidentical stem cells Ann NY Acad Sci 1999 872: 351 362
Seo SK, Regan A, Cihlar T, Lin DC . Cytomegalovirus ventriculoencephalitis in a bone marrow transplant recipient receiving antiviral maintenance: clinical and molecular evidence of drug resistance Clin Infect Dis 2001 33: 105 108
Limaye AP, Raghu G, Koelle DM . High incidence of ganciclovir-resistant cytomegalovirus infection among lung transplant recipients receiving preemptive therapy J Infect Dis 2002 185: 20 27
Small TN, Papadopoulos EB, Boulad F et al. Comparison of immune reconstitution after unrelated and related T-cell-depleted bone marrow transplantation: effect of patient age and donor leukocyte infusions Blood 1999 93: 467 480
Emery VC, Griffiths PD . Prediction of cytomegalovirus load and resistance patterns after antiviral chemotherapy Proc Natl Acad Sci USA 2000 97: 8039 8044
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Eckle, T., Lang, P., Prix, L. et al. Rapid development of ganciclovir-resistant cytomegalovirus infection in children after allogeneic stem cell transplantation in the early phase of immune cell recovery. Bone Marrow Transplant 30, 433–439 (2002). https://doi.org/10.1038/sj.bmt.1703666
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/sj.bmt.1703666
Keywords
This article is cited by
-
Analysis of human cytomegalovirus glycoprotein N genotypes in Chinese hematopoietic stem cell transplant recipients
Archives of Virology (2011)
-
Unrelated donor or partially matched related donor peripheral stem cell transplant with CD34+ selection and CD3+ addback for pediatric patients with leukemias
Bone Marrow Transplantation (2006)