Prophylactic transfer of CD8-depleted donor lymphocytes after T-cell–depleted reduced-intensity transplantation

RG Meyer, CM Britten, D Wehler, K Bender, G Hess… - Blood, 2007 - ashpublications.org
RG Meyer, CM Britten, D Wehler, K Bender, G Hess, A Konur, UF Hartwig, TC Wehler…
Blood, 2007ashpublications.org
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
posttransplantation 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 days 60 and 120 after …
Abstract
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 posttransplantation 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 days 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 2 patients with HLA-C–mismatched donors showed grade II and III acute GVHD and subsequently progressed to limited chronic GVHD. Following DLIs, 4 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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