Phase I study of high-stringency CD8 depletion of donor leukocyte infusions after allogeneic hematopoietic stem cell transplantation

G Orti, M Lowdell, A Fielding, E Samuel, K Pang… - …, 2009 - journals.lww.com
G Orti, M Lowdell, A Fielding, E Samuel, K Pang, P Kottaridis, E Morris, K Thomson, K Peggs
Transplantation, 2009journals.lww.com
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 …
Abstract
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× 10 6 CD4 cells/kg in recipients of unrelated and 3× 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× 10 6 (range 1× 10 6–43× 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.
Lippincott Williams & Wilkins