INFLUENCE OF CD34 CELL SELECTION ON THE INCIDENCE OF MIXED CHIMERISM AND MINIMAL RESIDUAL DISEASE AFTER ALLOGENEIC UNRELATED DONOR TRANSPLANTATION

Marrow transplantation from unrelated donors has been linked with an i ncreased risk of graft-versus-host disease (GVHD). In an attempt to lo wer the risk of acute GVHD we used CD34 marrow cell selection for T ce ll depletion. Since T cell depletion has been linked to an increased r isk of relapse and an increased risk of marrow failure, we used PCR am plification of minisatellite sequences to investigate donor cell engra ftment and RT-PCR amplification of recurrent chromosomal translocation s to investigate the residual disease post-transplant. Twenty-three pa tients who underwent BMT after positive selection of the CD34-positive cell population were studied. Results were then compared with those o f 37 patients who underwent transplantation with unmanipulated marrow graft. Among the 23 patients who received CD34(+) selected cell grafts , seven (30%) had evidence of full donor engraftment, 14 had evidence of residual recipient cells (61%), one had a non-take, and one autolog ous bone marrow recovery. Analysis of the chimaerism status post-trans plant in 36 patients who received unmanipulated marrow grafts showed t hat 31 patients (86%) had evidence of full donor engraftment. The diff erence in the incidence of mixed chimaerism profile between patients w ho received unmanipulated marrow graft and those receiving CD34(+) sel ected cell grafts was statistically significant (P<0.01). Nine patient s who received CD34(+) selected cell grafts could be analysed for the presence of minimal residual disease post-transplant (one with t(9;22) acute lymphoblastic leukaemia and eight with CML). In the patient tra nsplanted for a Ph-positive acute leukaemia, and in two out of the eig ht patients with CML, the search fora fusion transcript was consistent ly negative after transplantation. Among the six patients with evidenc e of residual disease, three patients also had a mixed chimaerism prof ile and were given donor lymphocyte infusions. Minimal residual diseas e study was performed post-transplant in 16 patients who received unma nipulated marrow grafts. In 10 of 14 patients with CML, and in two pat ients with acute leukaemia the search for a fusion transcript was cons istently negative after transplantation. The difference in the inciden ce of minimal residual disease between patients who received an unmani pulated marrow graft and those receiving CD34(+) selected cell grafts was not statistically significantly significant, but numbers of patien ts included in this analysis are still few. In conclusion, our study h ighlights the strong influence of graft manipulation on the incidence of mixed chimaerism after transplantation from an unrelated donor.