Making Space For Donor Cells

Immature progenitor cells occupy defined niches within the marrow stroma to obtain the necessary support for proliferation and differentiation.12 To allow access for donor cells to these niches, it was commonly believed that at least some host stem cells must be eradicated by the conditioning regimen. However, there is now evidence that allogeneic grafts can create their own marrow space via subclinical graft-versus-host reactions. First, dogs conditioned only with 4.5 Gy irradiation targeted to the cervical, thoracic, and upper abdominal lymph node chains, and administered postgrafting immunosuppression with mycophe-nolate mofetil (MMF, a purine synthesis inhibitor) and cyclosporine (CSP) achieved long-term mixed hematopoietic chimerism, as well as in the lymph nodes and bone marrow spaces that were shielded from irradiation.13 Secondly, HLA-identical bone marrow can stably engraft without any conditioning regimen or postgrafting immunosuppression in infants with severe combined immunodeficiency disease (SCID).14 Thirdly, allografts have been successfully carried out with postgrafting immunosuppression with MMF and CSP, but without conditioning in some human patients with T-cell deficiencies other than SCID.15 Finally, sustained engraftment has been accomplished in dogs after selective T-cell ablation with bis-muth-213-labeled anti-TCRap monoclonal antibody and postgrafting MMF/CSP.16

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