T-CELL-DEPLETED ALLOGENEIC BONE-MARROW TRANSPLANTATION FOR ACUTE-LEUKEMIA USING CAMPATH-1 ANTIBODIES AND POSTTRANSPLANT ADMINISTRATION OF DONORS PERIPHERAL-BLOOD LYMPHOCYTES FOR PREVENTION OF RELAPSE

One hundred and forty-six patients with acute leukaemia (81 with ANLL and 65 with ALL) received allogeneic bone marrow transplantation from their fully matched siblings. 121 patients underwent T-cell depletion (TCD) using Campath 1 monoclonal rat anti-human lymphocyte (CDw52) ant ibodies; 67 with Campath 1M and 54 with Campath 1G isotypes. Patients were conditioned for transplant using either total body irradiation co mbined with chemotherapy (125 patients) or busulfan and cyclophosphami de (21 patients). 112 recipients of T-cell depleted allografts receive d in addition total lymphoid irradiation (TLI) for prevention of rejec tion, Engraftment of neutrophils (>0.5 x 10(9)/l) and platelets (>25 x 10(9)/l) occurred on days 15 and 18, and on days 18 and 20 in recipie nts of Campath 1M and Campath 1G treated marrows respectively. Rejecti on was documented in 6.8% of T-cell depleted transplants. Leukaemia re lapse-free survival at 2 years was 83% for patients transplanted in fi rst CR, 76% in second CR (P-2 = 0.34) and 42% in advanced leukaemia (P -2 = 0.009). 81 marrow recipients, 38 with Campath 1M and 43 with Camp ath 1G treated marrow, received post-transplant graded increments of d onor's peripheral blood lymphocytes (PBL) to induce graft-versus-leuka emia (GVL) effects. Administration of donor's PBL was associated with clinically significant GVHD and with decreased relapse rate especially in patients with ALL. Our data suggest that in patients receiving mar row allografts depleted of T cells by Campath 1 monoclonal antibodies, rejection can be reduced by adequate pregrafting immunosuppression. I n patients with advanced disease, post-transplant cell-mediated immuno therapy (CMI) using donor's PBL may be beneficial; however, further st udies are needed to define the optimal schedule of CMI for safe and ef fective prevention of relapse following TCD bone marrow transplantatio n in malignant haematological diseases.