chapter  24
16 Pages

Donor lymphocyte infusions Francesco Dazzi, Hans J Stauss

RELAPSE OF CML AFTER ALLOGENEIC SCT: THE IMMUNOLOGIC SCENARIO

Allogeneic stem cell transplantation (SCT) is the only approach capable of curing chronic myeloid leukaemia (CML).1,2 However, a proportion of patients can relapse. The actuarial probability of relapse is very low for patients allografted in chronic phase with unmanipulated marrow cells and with the use of cyclosporin alone as prophylaxis for graft-versus-host disease (GVHD). However, the incidence of relapse becomes much higher when the transplant is performed in patients in advanced phase3 and when the GVHD prophylaxis is more intensive.4 In particular, the observation that the use of T-cell-depleted stem cells significantly increases the incidence of relapse provided prima facie evidence that allogeneic T cells play a pivotal role in eradicating leukaemic cells and/or maintaining remission.4,5

Allogeneic SCT allows donor allogeneic haematopoiesis to be established in the recipient. This event implies that recipient T cells reacting against donor cells are deleted or anergized so that donor cells are recognized as self (transplantation tolerance). Furthermore, disappearance of GHVD correlates with the deletion

of anti-recipient donor T cells,6,7 so that, in the case of relapse, some of the recipient leukaemic cells cannot be recognized by the donor T-cell repertoire. However, this chimeric condition provides the opportunity to exploit lymphocytes from the original donor once again, without any immunosuppressive regimen, to kill leukaemic cells.