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Blood, 1 January 2007, Vol. 109, No. 1, pp. 374-382.
Prepublished online as a Blood First Edition Paper on August 29, 2006; DOI 10.1182/blood-2006-03-005769.
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Submitted March 9, 2006
Accepted August 10, 2006
Prophylactic transfer of CD8-depleted donor lymphocytes after T-cell depleted reduced-intensity transplantation
Ralf G Meyer, Cedrik M Britten, Daniela Wehler, Klaus Bender, Georg Hess, Abdo Konur, Udo F Hartwig, Thomas C Wehler, Andrew J Ullmann, Chiara Gentilini, Lutz Uharek, Christoph Huber, Karin Kolbe, and Wolfgang Herr*
Department of Medicine III, Johannes Gutenberg University, Mainz
Department of Legal Medicine, Johannes Gutenberg University, Mainz
Department of Medicine III, Charite, Campus Benjamin-Franklin, Berlin
* Corresponding author; email: w.herr{at}3-med.klinik.uni-mainz.de.
Allogeneic hematopoietic stem-cell transplantation (SCT) regimens incorporating the lymphocytotoxic CD52 antibody alemtuzumab demonstrate efficient engraftment and reduced graft-versus-host disease (GVHD). However, these protocols substantially impair post-transplant antiviral and antitumor immunity. To accelerate immune reconstitution after alemtuzumab-based reduced-intensity SCT, we administered prophylactic CD8-depleted donor lymphocyte infusions (DLIs) starting on day 60 and 120 after transplantation. DLIs were processed in an immunomagnetic good manufacturing practice depletion procedure resulting in a 2.5 to 6-log reduction in CD8 T cells. Of 23 high-risk patients with hematologic malignancies, 11 received a total of 21 CD8-depleted DLIs. Five patients developed transient grade I acute GVHD following transfer. Only two patients with HLA-C-mismatched donors showed grade II and III acute GVHD and subsequently progressed to limited chronic GVHD. Following DLIs, four patients with declining hematopoietic donor chimerism converted to full chimeras. A 2.1-fold median increase of circulating CD4 T cells was observed within 2 weeks after infusion. Non-DLI patients did not show a comparable rise in CD4 counts. Four patients demonstrated enhanced frequencies of cytomegalovirus-specific CD4 and CD8 T cells following transfer. Our results suggest that prophylactic CD8-depleted DLIs accelerate immune reconstitution after lymphodepleted HLA-matched SCT and carry a low risk of inducing severe GVHD.
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