Adoptive immunotherapy with unselected or EBV-specific T cells for biopsy-proven EBV(+) lymphomas after allogeneic hematopoietic cell transplantation Journal Article


Authors: Doubrovina, E.; Oflaz-Sozmen, B.; Prockop, S. E.; Kernan, N. A.; Abramson, S.; Teruya-Feldstein, J.; Hedvat, C.; Chou, J. F.; Heller, G.; Barker, J. N.; Boulad, F.; Castro-Malaspina, H.; George, D.; Jakubowski, A.; Koehne, G.; Papadopoulos, E. B.; Scaradavou, A.; Small, T. N.; Khalaf, R.; Young, J. W.; O'Reilly, R. J.
Article Title: Adoptive immunotherapy with unselected or EBV-specific T cells for biopsy-proven EBV(+) lymphomas after allogeneic hematopoietic cell transplantation
Abstract: We evaluated HLA-compatible donor leukocyte infusions (DLIs) and HLA-compatible or HLA-disparate EBV-specific T cells (EBV-CTLs) in 49 hematopoietic cell transplantation recipients with biopsy-proven EBV-lymphoproliferative disease (EBV-LPD). DLIs and EBV-CTLs each induced durable complete or partial remissions in 73% and 68% of treated patients including 74% and 72% of patients surviving ≥ 8 days after infusion, respectively. Reversible acute GVHD occurred in recipients of DLIs (17%) but not EBV-CTLs. The probability of complete response was significantly lower among patients with multiorgan involvement. In responders, DLIs and EBV-CTLs regularly induced exponential increases in EBV-specific CTL precursor (EBV-CTLp) frequencies within 7-14 days, with subsequent clearance of EBV viremia and resolution of disease. In nonresponders, EBV-CTLps did not increase and EBV viremia persisted. Treatment failures were correlated with impaired T-cell recognition of tumor targets. Either donor-derived EBV-CTLs that had been sensitized with autologous BLCLs transformed by EBV strain B95.8 could not lyse spontaneous donor-derived EBV-transformed BLCLs expanded from the patient's blood or biopsied tumor or they failed to lyse their targets because they were selectively restricted by HLA alleles not shared by the EBV-LPD. Therefore, either unselected DLIs or EBV-specific CTLs can eradicate both untreated and Rituxan-resistant lymphomatous EBV-LPD, with failures ascribable to impaired T-cell recognition of tumor-associated viral antigens or their presenting HLA alleles. © 2012 by The American Society of Hematology.
Journal Title: Blood
Volume: 119
Issue: 11
ISSN: 0006-4971
Publisher: American Society of Hematology  
Date Published: 2012-03-15
Start Page: 2644
End Page: 2656
Language: English
DOI: 10.1182/blood-2011-08-371971
PROVIDER: scopus
PUBMED: 22138512
PMCID: PMC3311278
DOI/URL:
Notes: --- - "Cited By (since 1996): 1" - "Export Date: 2 April 2012" - "CODEN: BLOOA" - "Source: Scopus"
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