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Blood, 15 September 2007, Vol. 110, No. 6, pp. 1924-1932.
Prepublished online as a Blood First Edition Paper on May 15, 2007; DOI 10.1182/blood-2007-03-076844.
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Submitted March 1, 2007
Accepted May 13, 2007
Graft-versus-leukemia effects associated with detectable Wilms tumor-1 specific T lymphocytes following allogeneic stem cell transplantation for acute lymphoblastic leukemia (ALL)
Katayoun Rezvani*, Agnes S.M. Yong, Bipin N. Savani, Stephan Mielke, Keyvan Keyvanfar, Emma Gostick, David A. Price, Daniel C. Douek, and A. John Barrett
Stem Cell Allotransplantation Section, Hematology Branch, NHLBI, National Institutes of Health, Bethesda, MD, United States
Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Oxford, United Kingdom
Human Immunology Section, Vaccine Research Center, National Institute of Allergy & Infectious Diseases, National Institutes of Health, Bethesda, MD, United States
* Corresponding author; email: rezvanik{at}nhlbi.nih.gov.
To determine whether the leukemia-associated Wilms tumor antigen (WT1) contributes to a graft-versus-leukemia (GVL) effect following allogeneic stem cell transplantation (SCT) for acute lymphoblastic leukemia (ALL), we studied CD8+ T-cell responses to WT1 in 10 HLA-A*0201 positive ALL patients during the early phase of immune recovery post-SCT (days 30-120). Seven of 10 patients had detectable WT1 expression in their peripheral blood (PB) pre-SCT by quantitative reverse-transcription PCR (qRT-PCR). Using WT1/HLA-A*0201 tetramers and intracellular interferon-gamma (IFN- ) staining, post-SCT WT1+CD8+ T-cell responses were found only in patients with detectable WT1 expression pre-SCT (5/7 vs. 0/3, P < 0.05). To monitor the kinetics of WT1+CD8+ T-cell responses and disease regression post-SCT, absolute WT1+CD8+ T-cell numbers and WT1 expression were studied for each time-point. The emergence of WT1+CD8+ T-cells was associated with a decrease in WT1 expression, suggesting a WT1-driven GVL effect. Loss of WT1+CD8+ T-cell responses was associated with reappearance of WT1 transcripts, consistent with a molecular relapse (P < 0.001). WT1+CD8+ T-cells had a predominantly effector-memory phenotype (CD45RO+CD27-CD57+) and produced IFN-. Our results support the immunogenecity of WT1 after SCT for ALL and highlight the potential for WT1 vaccines to boost GVL after SCT for ALL.
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