Phase I Study of High-Stringency CD8 Depletion of Donor Leukocyte Infusions After Allogeneic Hematopoietic Stem Cell Transplantation
2009
Background. Donor leukocyte infusions (DLI) are given after hematopoietic stem-cell transplantation to eradicate persistent tumor or correct mixed chimerism (MC). The drawback of DLI is the risk of graft-versus-host disease (GVHD). In this phase I study, we examined the potential of highly extensive CD8 depletion of DLI as a means of improving its safety profile.Methods. High-stringency immunomagnetic CD8 depletion of DLI was performed after steady state donor apheresis. Patients with persistent disease or MC received escalated dose CD8-depleted DLI at 3-month intervals starting from 6 months posttransplantation. The starting dose was 1 x 10(6) CD4 cells/kg in recipients of unrelated and 3 x 10(6) CD4 cells/kg in recipients of related donor transplantations.Results. Twenty-eight patients received CD8-depleted DLI (n = 16 unrelated or mismatched, n = 12 human leukocyte antigen-identical sibling). Median CD8 depletion was more than 4 log. The median overall dose of CD4(+) cells/kg given was 4 x 10(6) (range 1 x 10(5)-43 x 10(6)). Conversion from MC to full donor chimerism was observed in 8 of 16 evaluable patients, and disease responses occurred in 5 of I I patients (complete response in four and partial response in one). Five of 28 patients developed severe acute pattern (grade II-IV) GVHD. Two patients died as a result of complications relating to GVHD.Conclusions. Graft-versus-tumor effects can be observed after high-stringency CD8-depleted DLI, although the major toxicity remains GVHD in this high-risk patient group. The safety and efficacy profile of this approach will require testing in a randomized controlled study.
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