Reconstitution of CD52-Negative CD4 T Cells after Alemtuzumab-Based T Cell Depleted Allogeneic Hematopoietic Stem Cell Transplantation

Abstract The human CD52 molecule is the target of the monoclonal antibody Alemtuzumab, which is used for treating patients with chemo-refractory chronic lymphocytic leukemia as well as for T cell depletion (TCD) in the context of allogeneic hematopoietic stem cell transplantation (HSCT). The molecule is expressed on the surface of lymphocytes, dendritic cells and to a lesser extent on blood-derived monocytes. Previously, investigators have demonstrated that the surface expression of CD52 on T cells is down-regulated after in vitro incubation with Alemtuzumab. By treating purified human CD4 T cells over 4 hours with 10 μg/mL Alemtuzumab in medium supplemented with 10% human AB serum in vitro…

313: A cDNA-based assay for donor-chimerism analysis of epidermal langerhans cells

CD8-Depleted Donor Lymphocyte Infusions Convert Mixed into Complete Donor T-Cell Chimerism after T-Cell Depleted Allogeneic Stem Cell Transplantation.

Abstract Donor lymphocyte infusions (DLI) are increasingly used to treat minimal residual disease or mixed hematopoietic donor-recipient chimerism in T-cell depleted allogeneic stem cell transplantation (SCT). In addition, several clinical trials currently investigate the prophylactic application of DLI to promote donor T-cell reconstitution after transplantation. However, DLI carry a substantial risk of inducing graft-versus-host disease (GVHD). We investigate DLI heavily depleted of CD8 T cells using a clinical grade immunomagnetic in vitro procedure in an ongoing clinical study [Meyer et al., Blood2007, 109:374]. These DLI are administered in a prophylactic setting to patients with hemat…

Donor CD4 T cells convert mixed to full donor T-cell chimerism and replenish the CD52-positive T-cell pool after alemtuzumab-based T-cell-depleted allo-transplantation.

Donor lymphocyte infusions (DLI) are used to resolve mixed T-cell chimerism (TCC) after allo-SCT despite a substantial risk of GVHD. We analyzed the impact of prophylactic CD8-depleted (CD8(depl)) DLI in 20 recipients of anti-CD52 alemtuzumab in vivo T-cell-depleted allografts with declining donor TCC after day +60. A total of 13 patients received CD8(depl) DLI and 7 patients did not. All but one of the DLI patients converted to complete donor T-cell chimeras, whereas only one non-DLI patient converted spontaneously. DLI induced transient acute GVHD in five and extensive chronic GVHD in two patients. These data suggest the use of CD8(depl) DLI as an effective treatment for mixed TCC, partic…

Follow Up On CD8-Depleted Donor-Lymphocyte Infusions After T-Cell Depleted Allogeneic Hemopoietic Stem Cell Transplantation

We applied prophylactic CD8-depleted (CD8depl) donor lymphocyte infusions (DLI) in the setting of T-cell depleted reduced-intensity allogeneic hematopoietic stem cell transplantation (HSCT) in a phase I/II trial. T-cell depletion was carried out by the use of high-dose Alemtuzumab (100 mg or 60 mg for unrelated or sibling donor transplantation, respectively). We have demonstrated the feasibility of this approach after having treated 23 patients in this protocol (Meyer et al. Blood 2007). From 2004 to 2011, 134 patients with different hematologic diseases were included and followed for a median observation time of 1.5 years after transplantation (range, 1.5-9 years). Median age was 56 years …

A PCR-Based Assay for the Detection of Langerhans-Cell Chimerism after Allogeneic Stem Cell Transplantation.

Abstract Early acute GVHD of the skin frequently occurs in patients after allogeneic hematopoietic stem cell transplantation. Although T cell depletion reduces the incidence and severity, it does not completely prevent skin GVHD. This leads to a prolonged need for immunosuppressive medication in a significant number of patients. For the induction of acute GVHD, the stimulation of donor T cells by residing host antigen presenting cells such as Langerhans cells of the skin (LCs) plays a central role. The absence of donor T cells after depletion, however, seems to hamper an early switch of LCs from host to donor origin. Therefore, the monitoring of LC chimerism is of great interest. We and oth…