Induction of graft-versus-leukemia to prevent relapse after partially lymphocyte-depleted allogeneic bone marrow transplantation by pre-emptive donorleukocyte infusions

In this prospective study we analyzed pre-emptive donor leukocyte infusions (DLI) in 82 consecutive patients transplanted with partially T cell-deplet ed grafts for acute myeloid leukemia, acute lymphoid leukemia, chronic myel oid leukemia, refractory anemia with excess of blasts, refractory anemia wi th excess of blasts in transformation and multiple myeloma. Donors were HLA -identical siblings, Patients without significant acute (>grade 1) and/or c hronic GVHD were scheduled to be treated with DLI (35 patients) and 31 actu ally received DLI. Patients who developed acute GVHD >grade 1 and/or chroni c GVHD were not scheduled to receive DLI and served as a comparison group ( 47 patients). The median interval between SMT and DLI was 22 weeks. The fir st six patients received 0.7 x 10(8) CD3(+) cells/kg body weight (b.w.). Fi ve out of these six patients developed acute GVHD (grade 1: n=2, grade 3: n =2 and grade 4: n=1) which was more frequent and more severe than we had an ticipated. In the next 25 patients the number of T lymphocytes was diminish ed to 0.1 x 10(8) CD3(+) cells/kg b.w. which resulted in less frequent and less severe GVHD. Eight patients in this group developed acute GVHD (grade 1: n=4, grade 2: n=4) and three patients had limited chronic GVHD. Patients in the DLI group needed more time to establish complete donor chimerism co nfirmed by a higher number of mixed chimeras at 6 months after BMT. The pro jected 3-year probability of disease-free survival was 77% for the 35 patie nts intended to treat with DLI and 45% for the patients of the comparison g roup (P=0.024). Relapse rate at 36 months after transplantation was 18% in the patients who were intended to treat with DLI and 44% in the comparison group (P=0.026). We conclude that preemptive DLI is feasible and generates favorable relapse rates in patients who are at high risk for relapse. Furth ermore, the incidence and severity of GVHD disease after DLI is dependent o n the number of CD3(+) cells infused.