期刊
AMERICAN JOURNAL OF TRANSPLANTATION
卷 6, 期 9, 页码 2121-2133出版社
WILEY
DOI: 10.1111/j.1600-6143.2006.01434.x
关键词
bone marrow transplantation; kidney; limiting dilution assay; mixed chimerism; multiple myeloma; tolerance
资金
- NHLBI NIH HHS [R01 HL63474] Funding Source: Medline
- NIAID NIH HHS [R21 AI037692, R01 AI037692-10, R01 AI037692-09, R21 AI037692-06, R01 AI037692] Funding Source: Medline
Six patients with renal failure due to multiple myeloma (MM) received simultaneous kidney and bone marrow transplantation (BMT) from HLA-identical sibling donors following nonmyeloablative conditioning, including cyclophosphamide (CP), peritransplant antithymocyte globulin and thymic irradiation. Cyclosporine (CyA) was given for approximately 2 months posttransplant, followed by donor leukocyte infusions. All six patients accepted their kidney grafts long-term. Three patients lost detectable chimerism but accepted their kidney grafts off immunosuppression for 1.3 to > 7 years. One such patient had strong antidonor cytotoxic T lymphocyte (CTL) responses in association with marrow rejection. Two patients achieved full donor chimerism, but resumed immunosuppression to treat graft-versus-host disease. Only one patient experienced rejection following CyA withdrawal. He responded to immunosuppression, which was later successfully withdrawn. The rejection episode was associated with antidonor Th reactivity. Patients showed CTL unresponsiveness to cultured donor renal tubular epithelial cells. Initially recovering T cells were memory cells and were enriched for CD4(+)CD25(+) cells. Three patients are in sustained complete remissions of MM, despite loss of chimerism in two. Combined kidney/BMT with nonmyeloablative conditioning can achieve renal allograft tolerance and excellent myeloma responses, even in the presence of donor marrow rejection and antidonor alloresponses in vitro.
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