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Mixed Chimera Converted Into Full Donor Chimera With Powerful Graft-Versus-Leukemia Effects but No Graft-Versus-Host Disease After Non T Cell-Depleted HLA-mismatched Peripheral Blood Stem Cell Transplantation

B Y Wu, K Y Guo, C Y Song, Yang, D Li

Bone Marrow Transplant. 2000 Sep;26(6):691-3.

PMID: 11035376

Abstract:

Instead of donor T cell depletion, we used CTLA4 and TJU103 (a small organic compound believed to block CD4 binding to MHC II molecule of APC) to block donor T lymphocyte activation in vitro before infusion, and mycophenolate mofetil to control the activity of lymphocytes of the recipient. We successfully treated a patient with an HLA-mismatched graft without donor T cell depletion. Mixed chimerism was observed 30 days and 60 days after transplantation. STR-PCR showed that 28% and 62% of blood mononuclear cells (MNC) were donor derived at day +30 and day +60, respectively. Mixed chimerism converted into full donor chimerism, when 99.7% of the MNC in the recipient were donor derived after three courses of DLI. A powerful GVL effect related to mixed chimerism was observed. No acute GVHD occurred, only grade II chronic GVHD occurred 6 months after transplant. Based on this case, we suggest that: (1) stable mixed chimerism can be intentionally established across HLA barriers without donor T cell depletion; (2) mixed chimerism can be converted into full donor chimerism by DLI; (3) mixed chimerism induced with this approach can be associated with a very powerful GVL effect, and these may be enhanced by DLI, without severe GVHD.

Chemicals Related in the Paper:

Catalog Number Product Name Structure CAS Number Price
CS31042414 Mycophenolate Mofetil Related Compound A Mycophenolate Mofetil Related Compound A Price
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