Addition of a low fixed number of CD3+ cells to CD34-enriched allografts: effects on engraftment, graft-versus-host disease, and survival after related and unrelated peripheral stem cell transplantation.
Despite prophylaxis with immunosuppressive drugs, severe graft-versus-host disease (GVHD) remains a major cause of morbidity and mortality following allogeneic stem cell transplantation. T cell depletion of the graft has decreased incidence and severity of GVHD but has resulted in a higher incidence of graft failure and relapse. To reduce the risk of severe GVHD, but at the same time to maintain the graft-versus-tumor effect, we administered a fixed low number of 1 x 10(5) donor T cells per kilogram of body weight to recipients of CD34(+) cell-enriched allogeneic peripheral blood stem cells (PBSCs). Donor lymphocyte infusions (DLI) were then given in incremental doses when mixed chimerism persisted or signs of relapse occurred. A total of 23 patients receiving allografts from related and unrelated donors were treated according to this protocol after myeloablative or reduced intensity conditioning. One patient did not engraft and 3/20 evaluable patients developed acute (a) GVHD > or = grade II, with a corresponding estimated cumulative incidence of 15.6% (95% CI 0-30.5%). DLI (n = 13) induced aGVHD > or = II in 6 patients, but the severity of the syndrome was reduced. Overall GVHD-related mortality was low (13%). The probability of disease-free survival and overall survival at 2 years was 0.40 (95% CI 0.21-0.75) and 0.36 (95% CI 0.21-0.63). Progression-free survival and overall survival was significantly better in patients with acute or chronic myelogenous leukemia compared to patients with lymphoproliferative disorders (p = 0.002; p = 0.02). We conclude that the combination of allografts with a T cell content of about 1 x 10(5)/kg and escalating doses of DLI is a viable transplant strategy in patients with myeloid leukemias, which results in stable engraftment and a reduction of mortality from aGVHD.
Goerner
Martin
M
German Cancer Research Center, Clinical Cooperation Unit, Molecular Hematology/Oncology, D-69115 Heidelberg, Germany. martin_goerner@med.uni-heidelberg.de
Weber-Nordt
Renate
R
Hoepfner
Sabine
S
Benner
Axel
A
Luft
Thomas
T
Ho
A D
AD
D000328:Adult; D015703:Antigens, CD / Q000097:blood*; D018952:Antigens, CD34 / Q000097:blood*; D017252:CD3 Complex / Q000097:blood*; D002469:Cell Separation / Q000379:methods; D016572:Cyclosporine / Q000627:therapeutic use; D018572:Disease-Free Survival; D004359:Drug Therapy, Combination; D005260:Female; D006085:Graft Survival; D006086:Graft vs Host Disease / Q000453:epidemiology* / Q000517:prevention & control; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007938:Leukemia / Q000145:classification / Q000401:mortality / Q000628:therapy; D008228:Lymphoma, Non-Hodgkin / Q000401:mortality / Q000628:therapy; D008297:Male; D008727:Methotrexate / Q000627:therapeutic use; D008875:Middle Aged; D009101:Multiple Myeloma / Q000401:mortality / Q000628:therapy; D009173:Mycophenolic Acid / Q000031:analogs & derivatives* / Q000627:therapeutic use; D033581:Stem Cell Transplantation / Q000379:methods; D016019:Survival Analysis; D013997:Time Factors; D014184:Transplantation, Homologous / Q000502:physiology*
D015703:Antigens, CD; D018952:Antigens, CD34; D017252:CD3 Complex; D007166:Immunosuppressive Agents; D016572:Cyclosporine; D009173:Mycophenolic Acid; D008727:Methotrexate