A strategy to achieve donor-specific hyporesponsiveness in cadaver renal allograft recipients by donor haematopoietic stem cell transplantation into the thymus and periphery.

A strategy to achieve donor-specific hyporesponsiveness in cadaver renal allograft recipients by donor haematopoietic stem cell transplantation into the thymus and periphery.
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通过将供体造血干细胞移植到胸腺和外周来实现尸体肾同种异体移植受者的供体特异性低反应性的策略。

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发表时间:
2004
影响因子:
--
通讯作者:
Varsha B. Trivedi
Varsha B. Trivedi
中科院分区:
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文献类型:
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作者:
H. Trivedi;A. Vanikar;J. M. Vakil;V. Shah;P. Modi;Varsha B. Trivedi

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INTRODUCTION We designed a prospective, randomized clinical trial to evaluate the immune response to thymic and peripheral infusions of donor haematopoietic stem cells (HSCs) to create tolerance in recipients of cadaver renal allografts. METHOD We divided 24 patients into two equal groups. For group A, 350 ml of unfractionated bone marrow (BM) was aspirated from the anterior iliac crests of donor cadavers. A 2 ml aliquot of concentrated marrow was infused into the thymus of the subject and 100 ml into the BM before surgery; the remaining 250 ml was infused peripherally post-transplantation. The mean nucleated cell count inoculated into the thymus was 3.3 x 10(4) cells/cm(3) and into the periphery 8.6 x 10(7) cells/kg body weight. Group B (controls) underwent renal transplantation directly. Recipients were lymphocytotoxicity cross-match negative in both groups. Group A received low dose prednisolone and cyclosporin; controls also received azathioprine. RESULTS Over a mean follow-up of 703 days for both groups, group A had significantly better graft function with minimum acute rejection episodes or cytomegalovirus (CMV) infections, a mean serum creatinine (SCr) of 1.23 mg/dl and no graft or patient loss. Group B, with a mean SCr of 2.19 mg/dl had three patients with single acute rejection episodes, two of whom died following uncontrolled rejection-associated infections. The third patient maintained an SCr of 2.5 mg%. Actuarial graft survival was 87.5% in controls at the end of 2 years compared with group A with 100% graft survival at the end of 2 years. CONCLUSION This novel approach of introducing unfractionated HSCs into the thymus and periphery to create tolerance is safe and efficacious and gives significantly better graft function, minimum acute rejection and no CMV disease with monotherapy.
胸腺移植耐受的方式。
DOI: 10.1681/asn.v591639
发表时间: 1995
期刊: Journal of the American Society of Nephrology : JASN
影响因子: --
作者:
Remuzzi,G;Perico,N;Carpenter,CB;Sayegh,MH
通讯作者: Sayegh,MH