Ex vivo T‐cell depletion with the monoclonal antibody Campath‐1 plus human complement effectively prevents acute graft‐versus‐host disease in allogeneic bone marrow transplantation

Abstract

We have developed a rapid and simple procedure for the elimination of mature T-cells from the donor marrow using a single incubation with the monoclonal antibody Campath-1 and donor complement. This resulted in a reduction of T-cell contamination to a mean of 1%. This regimen reduced the incidence of acute graft-versus-host disease significantly in 21 consecutive bone marrow grafts in 18 patients with leukaemia and non-Hodgkin's lymphoma. Purging was responsible for an increased incidence of graft rejection in HLA-identical transplants (13%).

In vivo T cell depletion with pretransplant anti-thymocyte globulin reduces graft-versus-host disease without increasing relapse in good risk myeloid leukemia patients after stem cell transplantation from matched related donors

“…In smaller studies with T cell depletion a dramatic increase in relapse was seen in CML patients in chronic phase, 3,5 while in AML patient some centers reported no increase in relapse. 11,25 In a large study by the IBMTR, however, it could be clearly shown that T cell depletion caused a higher incidence of relapse in AML and CML, but the risk was lower in patients with AML than in patients with CML. 6 Attempts to overcome this high incidence of relapse by donor lymphocyte infusions were associated with a high incidence of acute and chronic GVHD.…”

“…The median time to leukocyte engraftment (Ͼ1 ϫ 10 9 /l) was 16 (range, 12-33) in the ATG group and 17 days (range, [11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29] in the non-ATG group (NS). Platelet engraftment (Ͼ20 ϫ 10 9 /l) was reached for the ATG group after a median of 24 days (range, 14-277) and for the non-ATG group after 19 days (range, 11-34) (P ϭ 0.002).…”

“…[7][8][9] Other forms of T cell depletion including T cell depletion with monoclonal antibodies either in vivo or ex vivo have been investigated extensively, resulting in a decrease of GVHD, but a relatively high incidence of graft failure has been observed. 10,11 By adding monoclonal anti-52 antibodies to the conditioning regimen to deplete residual host T cells, the problem of graft failure has been partly overcome. 12 Another strategy of in vivo T cell depletion is the use of anti-thymocyte globulin as part of the conditioning regimen.…”

Therapy of steroid-refractory acute GVHD with CD52 antibody alemtuzumab is effective

“…Licensed for the treatment of fludarabine-refractory B-cell CLL, 2 alemtuzumab was also used in T-cell tumors [3][4][5] and due to its known immunosuppressive activity in autoimmune diseases 6 and for GVHD prevention. 7,8 Although alemtuzumab in the treatment of acute and chronic GVHD in small studies and case reports has already shown therapeutic responses, [9][10][11][12][13] very recently Schnitzler et al 14 reported 20 patients with severe intestinal acute GVHD treated successfully with alemtuzumab. Here, we show the efficacy of alemtuzumab for intestinal and liver grade III and IV acute GVHD in 18 steroid-refractory patients and support the idea that smaller doses may be preferable.…”

Therapeutic role of alemtuzumab (Campath-1H) in patients who have failed fludarabine: results of a large international study

“…13 Binding of alemtuzumab to CD52 on target cells may cause cell death by 3 different mechanisms: complement activation, 14 antibody-dependent cellular cytotoxicity, 15,16 and apoptosis. 17 Based on prior reports from small studies demonstrating that alemtuzumab was an effective salvage therapy for patients in whom fludarabine had failed, 18 this study was implemented to confirm these encouraging results in a larger cohort of patients with advanced B-CLL.…”