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Annals of Oncology Advance Access published online on August 5, 2008
Annals of Oncology, doi:10.1093/annonc/mdn404
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© The Author 2008. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oxfordjournals.org

Clinical evidence of a graft-versus-lymphoma effect against relapsed diffuse large B-cell lymphoma after allogeneic hematopoietic stem-cell transplantation

M. R. Bishop1,*, R. M. Dean1,2, S. M. Steinberg3, J. Odom1, S. Z. Pavletic1, C. Chow4, S. Pittaluga5, C. Sportes1, N. M. Hardy1, J. Gea-Banacloche1, A. Kolstad6, R. E. Gress1 and D. H. Fowler1

1 Experimental Transplantation and Immunology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD
2 Cleveland Clinic Foundation, Cleveland, OH
3 Biostatistics and Data Management Section, Center for Cancer Research, National Cancer Institute
4 Diagnostic Radiology Department, Warren G. Magnuson Clinical Center
5 Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA
6 Norwegian Radium Hospital, Oslo, Norway

* Correspondence to: Dr M. R. Bishop, Experimental Transplantation and Immunology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Building 10, CRC Room 4-3152, 10 Center Drive, Bethesda, MD 20892, USA. Tel: +1-301-435-2764; Fax: +1-301-480-4354; E-mail: mbishop{at}mail.nih.gov

Background: A graft-versus-lymphoma effect against diffuse large B-cell lymphoma (DLBCL) is inferred by sustained relapse-free survival after allogeneic stem-cell transplantation; however, there are limited data on a direct graft-versus-lymphoma effect against DLBCL following immunotherapeutic intervention by either withdrawal of immunosuppression or donor lymphocyte infusion (DLI).

Materials and methods: An analysis was carried out to determine whether a direct graft-versus-lymphoma effect exists against DLBCL. The analysis was restricted to patients with DLBCL, who were either not in complete remission at day +100 after allogeneic stem-cell transplantation or subsequently relapsed beyond this time point.

Results: Fifteen patients were identified as either not in complete remission (n = 13) at their day +100 evaluation or subsequently relapsed (n = 2) and were assessed for subsequent responses after withdrawal of immunosuppression or DLI. Eleven patients were treated with either withdrawal of immunosuppression (n = 10) or a DLI (n = 1) alone; four patients received chemotherapy with DLI to reduce tumor bulk. Nine (60%) patients subsequently responded (complete = 8, partial = 1). Six responses occurred after withdrawal of immunosuppression alone. Six patients are alive (range 42–83+ months) in complete remission without further treatment.

Conclusion: The demonstration of sustained complete remission following immunotherapeutic intervention provides direct evidence of a graft-versus-lymphoma effect against DLBCL.

allogeneic, diffuse large B-cell lymphoma, graft-versus-lymphoma

Received for publication May 22, 2008. Accepted for publication May 28, 2008.


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