Donor Leukocyte Infusions for the Treatment of Leukemia Relapse After Allogeneic Hematopoietic Cell Transplantation with Myeloablative Conditioning

Leukemic relapse after allogeneic transplantation is a difficult problem. Conventional treatment modalities or second transplants have not provided the sustained complete remissions on the whole. Reinfusion and activation of cytotoxic T lymphocytes of the donor seem to be effective and it has been understood that the success of the transplantation depends mainly on graft versus leukemia effect. Thirteen patients with leukemia (8 CML, 5 AML) who had relapsed after allogeneic hematopoietic cell transplantation (HCT) with myeloablative conditioning, have received donor leukocyte infusions (DLI). The median time between transplantation and relapse was 18 months (4-57 months). For CML patients who had cytogenetic or hematologic relapse, IFN alpha 2b was started at a dose of 5 million units/m2/d for every consecutive days. Starting from the fifth week of this treatment, unprimed donor peripheral blood mononuclear cells were infused to the patients once a week for four weeks. IFN treatment was not cessated during these infusions, and was given for 12 weeks totally. For relapsed acute leukemia patients, standart chemotherapy regimens as for AML were used. After the treatment, donor lymphocytes which were obtained from the original HCT donor who was primed with G-CSF were given. After recovery, IFN alfa2b was started 5 million U/m2/d each consecutive day until the GVHD findings were observed. GVHD prophylaxis was not made after DLIs. Acute GVHD was seen in 11 of 13 patients. Four patients developed chronicGVHD. Among 13 patients, four patients are alive and they have been in complete remission for 23 to 76 months. The other patients were not alive due to mostly disease progression. Two patients died because of advanced GVHD. In our practice, the patients with progressive disease were not the well responded ones. These observations suggest that there is a limit for the immune effect regarding the number of the tumor cells and their proliferative capacity. Chemotherapy, which does not suppress immunity, may give time and chance to allogeneic lymphocytes to affect.