Pre-emptive immunotherapy with CD8-depleted donor lymphocytes after CD34-selected allogeneic peripheral blood stem cell transplantation.
OBJECTIVE
To maximize graft-versus-leukemia (GVL) effects while minimizing the risk of graft-versus-host disease (GVHD), we undertook a study of allogeneic CD34-selected peripheral blood stem cell (PBSC) transplantation followed by CD8-depleted donor lymphocyte infusion (DLI).


METHODS
Twenty-four patients with advanced hematologic malignancies were included. PBSC were collected in matched (N=16) or one-mismatch (N=8) related donors and CD34-selected. On day 60, donors donated lymphocytes that were CD8-depleted and separated into 3 aliquots containing 2 x 10(6), 1 x 10(7) and 5 x 10(7) CD3+ cells/kg (patients 1-13) or into 2 aliquots containing 1 x 10(7) and 5 x 10(7) CD3+ cells/kg (patients 14-24). The 1st aliquot was infused on day 60 and the other 1 (2) cryopreserved and infused on days 100 (and 140).


RESULTS
An average of 100%, 100% and 84% of the scheduled dose could be administered in DLI 1, 2 and 3, respectively. Although the study group was at very high risk of GVHD, the actuarial incidence of grade II-IV acute GVHD was 28% (13% for HLA-identical siblings) with only 1 patient developing grade III-IV GVHD (after DLI). The actuarial 2-year probability of extensive chronic GVHD was similarly low (13% for all patients and 0% for HLA-identical siblings). Individual cases as well as a 30% relapse rate (0% for standard-risk patients versus 55% for high-risk patients) indicated preservation of the GVL effect.


CONCLUSIONS
We conclude that allogeneic transplantation of CD34-selected PBSC followed by pre-emptive CD8-depleted DLI is feasible with rapid engraftment and minimizes the risk of severe GVHD. Large prospective trials are required to prove that it preserves the GVL effect fully.
Baron
Frédéric
F
Department of Medicine, Division of Hematology, University of Liège, CHU Sart-Tilman, 4000 Liège, Belgium.
Siquet
Jean
J
Schaaf-Lafontaine
Nicole
N
Baudoux
Etienne
E
Hermanne
Jean-Philippe
JP
Fillet
Georges
G
Beguin
Yves
Y
D000293:Adolescent; D000328:Adult; D016827:CD8 Antigens; D003586:Cytomegalovirus Infections / Q000209:etiology; D005240:Feasibility Studies; D005260:Female; D006085:Graft Survival; D006086:Graft vs Host Disease / Q000453:epidemiology / Q000517:prevention & control; D020544:Graft vs Leukemia Effect; D019337:Hematologic Neoplasms / Q000401:mortality / Q000628:therapy*; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects / Q000706:statistics & numerical data; D006648:Histocompatibility; D006801:Humans; D015994:Incidence; D007937:Leukapheresis; D008212:Lymphocyte Depletion; D017710:Lymphocyte Transfusion / Q000706:statistics & numerical data; D008297:Male; D008875:Middle Aged; D016019:Survival Analysis; D014184:Transplantation, Homologous / Q000706:statistics & numerical data; D016896:Treatment Outcome; D014775:Virus Activation
D016827:CD8 Antigens