Low-dose donor CD8+ cells in the CD4-depleted graft prevent allogeneic marrow graft rejection and severe graft-versus-host disease for chronic myeloid leukemia patients in first chronic phase.
Based on previous experiences in animals and humans, low doses of CD8+ lymphocytes infused together with the marrow graft seem to enhance engraftment after allogeneic T cell-depleted marrow transplantation. From April 1994 to February 1997, 12 patients with chronic myelogenous leukemia in first chronic phase receiving a bone marrow transplant (BMT) from an HLA-identical sibling were included in a pilot study of T cell subset depletion. Total depletion of CD4+ cells of the marrow graft and partial depletion of CD8+ cells was performed by immunomagnetic separation. In order to improve the engraftment rate, we infused a low fixed number of CD8+ lymphocytes (0.25 x 10(6)/kg). All the patients were at high risk of developing acute graft-versus-host disease (GVHD), with a recipient age of >30 years, and/or donor sensitized by previous pregnancies or transfusions. All of them received cyclosporin A and methotrexate post-BMT. No graft failure was observed. The grade III-IV GVHD rate was 16.6%, and the actuarial survival at 3 years is 81.8%. Immunological recovery showed persistent CD8+ HLA-DR+ lymphocytosis 8 months after transplant. Relapses were not observed. This experience shows the importance of CD8+ cells to ensure correct engraftment, decreasing the GVHD rate.
Gallardo
D
D
Department of Clinical Hematology, Hospital Duran i Reynals, Institut Català d'Oncologia, Barcelona, Spain.
García-López
J
J
Sureda
A
A
Canals
C
C
Ferra
C
C
Cancelas
J A
JA
Berlanga
J J
JJ
Brunet
S
S
Boqué
C
C
Picón
M
M
Torrico
C
C
Amill
B
B
Martino
R
R
Martínez
C
C
Martín-Henao
G
G
Domingo-Albós
A
A
Grañena
A
A
D000328:Adult; D001854:Bone Marrow Cells / Q000276:immunology; D016026:Bone Marrow Transplantation / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D016572:Cyclosporine / Q000627:therapeutic use; D005260:Female; D005434:Flow Cytometry; D006084:Graft Rejection / Q000517:prevention & control; D006086:Graft vs Host Disease / Q000517:prevention & control*; D006801:Humans; D016756:Immunoglobulins, Intravenous / Q000627:therapeutic use; D018189:Immunomagnetic Separation; D016130:Immunophenotyping; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000276:immunology / Q000401:mortality / Q000628:therapy*; D008297:Male; D008727:Methotrexate / Q000627:therapeutic use; D008875:Middle Aged; D010865:Pilot Projects; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D019172:Transplantation Conditioning; D014184:Transplantation, Homologous
D016756:Immunoglobulins, Intravenous; D007166:Immunosuppressive Agents; D016572:Cyclosporine; D008727:Methotrexate