The development of cellular immunity to Epstein-Barr virus after allogeneic bone marrow transplantation Journal Article


Authors: Lucas, K. G.; Small, T. N.; Heller, G.; Dupont, B.; O'Reilly, R. J.
Article Title: The development of cellular immunity to Epstein-Barr virus after allogeneic bone marrow transplantation
Abstract: Epstein-Barr virus-induced lymphoproliferative disease (EBV-LPD) is a potentially lethal complication during the first 6 months after allogeneic bone marrow transplantation (BMT). To determine whether deficiencies of EBV- specific cellular immunity contribute to EBV-LPD susceptibility and distinguish patients at risk, we performed limiting dilution analysis to quantify anti-EBV cytotoxic T-lymphocyte precursor (CTLp) frequencies in 26 recipients of unmodified or T cell-depleted (TCD) grafts from EBV- seropositive donors. At 3 months post-BMT (n = 26), only five patients had EBV CTLp frequencies in the range of seropositive normal controls, irrespective of the type of transplant administered. By 6 months post-BMT, 9 of 13 patients tested had EBV CTLp frequencies within the normal range. The time period in which these patients had deficient cellular immunity to EBV corresponds to the period in which we have observed EBV-LPD in most prior patients. One patient with a low EBV CTLp frequency at 4 months post-BMT developed an EBV-LPD. Within 2 weeks of receiving an infusion of donor peripheral blood mononuclear cells (PBMC) providing less than 1,200 EBV- specific cytotoxic T-cell precursors, populations of EBV-specific CTL in the circulation were restored to levels detected in normal seropositive adults. Concurrently, the patient achieved a regression of the EBV-LPD, which has been sustained without further therapy. These studies indicate that recipients of both unmodified and TCD marrow grafts have profound deficiencies of EBV-specific T cell-mediated immunity early posttransplant, and that the period of risk for EBV-LPD closely corresponds to this interval of severe deficiency. Treatment of one patient with EBV-LPD with marrow donor-derived PBMC induced a rapid expansion of EBV-specific cytotoxic T- cell populations that occurred contemporaneously with the clinical regression of disease.
Keywords: adolescent; adult; child; clinical article; controlled study; middle aged; transplantation, homologous; human cell; bone marrow; allogenic bone marrow transplantation; time factors; risk; lymphoma, b-cell; cellular immunity; mononuclear cell; cytotoxic t lymphocyte; t-lymphocytes, cytotoxic; tumor virus infections; lymphoproliferative disease; immunocompromised host; bone marrow transplantation; immunotherapy, adoptive; lymphocyte depletion; epstein barr virus; herpesvirus 4, human; immunity, cellular; herpesviridae infections; disease susceptibility; dilution; humans; human; priority journal; article
Journal Title: Blood
Volume: 87
Issue: 6
ISSN: 0006-4971
Publisher: American Society of Hematology  
Date Published: 1996-03-15
Start Page: 2594
End Page: 2603
Language: English
PUBMED: 8630428
PROVIDER: scopus
DOI: 10.1182/blood.V87.6.2594.bloodjournal8762594
DOI/URL:
Notes: Article -- Export Date: 22 November 2017 -- Source: Scopus
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MSK Authors
  1. Trudy Small
    234 Small
  2. Glenn Heller
    391 Heller
  3. Richard O'Reilly
    736 O'Reilly
  4. Bo Dupont
    262 Dupont