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.

Abstract

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.

• Authors: D Gallardo, J García-López, A Sureda, C Canals, C Ferra, J A Cancelas, J J Berlanga, S Brunet, C Boqué, M Picón, C Torrico, B Amill, R Martino, C Martínez, G Martín-Henao, A Domingo-Albós, A Grañena
• Journal: Bone marrow transplantation (Bone Marrow Transplant) Vol. 20 Issue 11 Pg. 945-52 (Dec 1997) ISSN: 0268-3369 [Print] England
• PMID: 9422473 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Immunoglobulins, Intravenous
• Immunosuppressive Agents
• Cyclosporine
• Methotrexate

Topics

• Adult
• Bone Marrow Cells (immunology)
• Bone Marrow Transplantation (immunology)
• CD4-Positive T-Lymphocytes (immunology)
• CD8-Positive T-Lymphocytes (immunology)
• Cyclosporine (therapeutic use)
• Female
• Flow Cytometry
• Graft Rejection (prevention & control)
• Graft vs Host Disease (prevention & control)
• Humans
• Immunoglobulins, Intravenous (therapeutic use)
• Immunomagnetic Separation
• Immunophenotyping
• Immunosuppressive Agents (therapeutic use)
• Leukemia, Myelogenous, Chronic, BCR-ABL Positive (immunology, mortality, therapy)
• Male
• Methotrexate (therapeutic use)
• Middle Aged
• Pilot Projects
• T-Lymphocyte Subsets (immunology)
• Transplantation Conditioning
• Transplantation, Homologous