Phase I study of high-stringency CD8 depletion of donor leukocyte infusions after allogeneic hematopoietic stem cell transplantation.
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.
Orti
Guillermo
G
Department of Haematology, Royal Free Hampstead NHS Trust, London, United Kingdom.
Lowdell
Mark
M
Fielding
Adele
A
Samuel
Edward
E
Pang
Kwok
K
Kottaridis
Panos
P
Morris
Emma
E
Thomson
Kirsty
K
Peggs
Karl
K
Mackinnon
Stephen
S
Chakraverty
Ronjon
R
D000328:Adult; D001781:Blood Component Removal; D001804:Blood Transfusion, Autologous; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000637:transplantation*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002470:Cell Survival; D005260:Female; D006086:Graft vs Host Disease / Q000276:immunology / Q000401:mortality; D019337:Hematologic Neoplasms / Q000276:immunology / Q000601:surgery / Q000628:therapy*; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D018189:Immunomagnetic Separation; D008131:London; D008212:Lymphocyte Depletion / Q000009:adverse effects / Q000379:methods; D017710:Lymphocyte Transfusion / Q000009:adverse effects / Q000379:methods*; D008297:Male; D008875:Middle Aged; D013997:Time Factors; D018183:Transplantation Chimera; D014184:Transplantation, Homologous; D016896:Treatment Outcome; D055815:Young Adult