Abstract 872 Poster Session II, Sunday, 5/2 (poster 134)
Adoptive immunotherapy is the administration of CD3 lymphocytes to patients who have already undergone bone marrow transplantation (BMT) in an attempt to promote a graft-versus-tumor effect or to reinforce engraftment. We reinfused lymphocytes from previous bone marrow donors in 4 children and 14 adults and compared results in these groups. Children ranged in age from 5 months to 10 years, mean 4.6± 1.9 years; while control group of adults ranged in age from 24 to 55 years, mean 41.6 ± 2.5 years. Diagnoses of children were AML (1), CML (1), aplastic anemia (1) and severe combined immunodeficiency (1). Diagnoses of adults were CML (5), AML (5), ALL (2), NHL (1), and myeloproliferative syndrome (1). All patients had previously undergone BMT at the University of Florida within the preceding 1 to 30 months (mean: 8.8 months ± 1.6). Patients received mean doses of CD3 cells/kg of 3.45×108 ± .7×108 ranging from 1×107 to 2.1×1010 cells, over one to six courses (mean: 2.0 ± .30 courses). Of 2 children who relapsed from their malignancies after bone marrow transplantation, both achieved remission with infusion of donor lymphocytes. Both children are still in remission, one 10+ months and the other 15+ months after lymphocyte reinfusions. In the 14 adults with relapsed disease after bone marrow transplantation who received donor lymphocytes, 6 achieved remission and are alive and well from 5 to 23 months after their adoptive immunotherapy. Eight patients died within 15 months after immunotherapy. Causes of death were graft-versus-host disease (GVHD), infection and intracranial bleed. In 1 child with aplastic anemia, chimerism of CD3 population after bone marrow was 80% donor and 20% recipient. This patient had incomplete response to BMT with stabilization of neutrophils at only 1000/mm3 and hematocrit only 24-26%. After additional lymphocyte infusion of 1 × 107 cells, donor cells displaced residual host cells and patients developed more complete donor marrow phenotype. Repeat chimerism studies showed 99% donor and 1% recipient; this was concurrent with significant increase in white blood cell counts to 4000/mm3. Donor lymphocyte reinfusion resulted in GVHD in 9 patients. Thus, reinfusion of donor lymphocytes can be used after BMT as a means of inducing graft-versus-tumor effects without the need for a second or third bone marrow transplant. It can also be used to displace residual host cells in children transplanted for aplastic anemia. Children tolerate the procedure well and have better results and fewer complications compared to adults. The major problem is potentially fatal GVHD. Adoptive immunotherapy should be considered in all children or adults who relapse or who have incomplete engraftment after BMT.
