The effect of T cell depletion with Campath-1M on immune reconstitution after chemotherapy and allogeneic bone marrow transplant as treatment for leukaemia

The prophylactic use of T cell depletion (TCD) strategies for the prevention of graft-versus-host disease (GVHD) following allogeneic stem cell transplantation remains widespread, Initial reports of high incidence of graft rejection after TCD BRIT led to a more away from this approach but improved conditioning regimens have reduced this risk substantially. The use of TCD has also been associated with higher relapse risk post-BRIT although the success of donor leukocyte infusion (DLI) as treatment for relapse has reduced this problem, especially in chronic myeloid leukaemia (CML), Currently the use of TCD BRIT is increasing particularly due to the relative increase in BRIT from non-related donors for whom TCD is the optimal GVHD prophylaxis. However, doubts remain over the long-term effect on the reconstituted immune system of recipients of TCD BRIT, particularly in adult recipients, In this study we have undertaken a detailed sequential analysis in 23 patients who received allo-grafts from HLA-identical sibling donors after high-dose chemo/radiotherapy for acute or chronic leukaemia, Of these patients, 11 received non-manipulated grafts, five received 'partially TCD' (PTCD) and a further seven received 'fully TCD' (FTCD) bone marrow, T cell depletion was performed ex vivo by Campath-1M plus autologous serum as a source of complement, Partial TCD describes grafts with a T cell reduction of 1-2 log, Full TCD refers to grafts with a reduction of >2.5 log, The decision regarding the optimal degree of TCD was clinical and was based upon the perceived relative risk of relapse based upon the disease and remission status, All patients were monitored for up to 12 months post-BRIT with regard to reconstitution of T and NIC cell subsets, T cell depletion at either level was associated with a slower recovery of CD4 cells, This was most marked in the FTCD recipients and lasted throughout the period of study, CD8 cell recovery was also slower in the TCD recipients but this normalised throughout the 12 months post-BRIT, The ratio of CD45RA(+):CD45RO(+) increased in all recipients after month 3, This suggests that a degree of extra-thymic T cell maturation can occur in recipients of allogeneic BRIT, NK cell recovery was more rapid in the TCD recipients and these differences were maintained throughout the first year.