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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(6)-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 11 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.

Original publication

DOI

10.1097/TP.0b013e3181bbf382

Type

Journal article

Journal

Transplantation

Publication Date

15/12/2009

Volume

88

Pages

1312 - 1318

Keywords

Adult, Blood Component Removal, Blood Transfusion, Autologous, CD4-Positive T-Lymphocytes, CD8-Positive T-Lymphocytes, Cell Survival, Female, Graft vs Host Disease, Hematologic Neoplasms, Hematopoietic Stem Cell Transplantation, Humans, Immunomagnetic Separation, London, Lymphocyte Depletion, Lymphocyte Transfusion, Male, Middle Aged, Time Factors, Transplantation Chimera, Transplantation, Homologous, Treatment Outcome, Young Adult