Prophylactic Transfer of Leukemia-reactive T Cells After Allogeneic Transplantation

Chronic Myeloid Leukemia

Adoptive immunotherapy, BCR-ABL reactive T cells, Allogeneic Transplantation

Efforts to decrease the risk of GvHD by depleting T cells from the graft in CML patients have been complicated by an increased incidence of leukemia-relapse. Newer protocols using CD34+ selected hematopoietic cells from matched-sibling donors and subsequent infusion of T cells in incremental doses to treat or avoid relapse of disease seem to be more promising. In this study, we try to further optimize this approach by the prophylactic infusion of cytotoxic T cells activated ex-vivo against leukemia-associated/specific antigens using peptide-pulsed dendritic cells.

The conditioning protocol contains: Total Body Irradiation 8-12 Gy (4-6 x 2 Gy, a 2 x/die) day -9 to-7 Thiotepa 10 mg/kg (2 x 5 mg/kg) day -5 Fludarabine 200 mg/m2 (5 x 40 mg/m2) day -6 to-2 ATG Fresenius 25 mg/kg (5 x 5 mg/kg) day -6 to-2 Cyclosporine A 1 mg/kg Day -10 to-3 on day 0 CD34+ cells after immunomagnetic selection are infused. \> 4 x 10e6/kg CD34 cells/kg are required. On days 28, 56 and 112 after transplantation, cytotoxic T cells generated in-vitro are infused in patients who do not have signs of acute GvHD. Regular follow-up compromises immune monitoring including Tetramer analyses of Peptide-reactive T cells

Germany