在体内 T 细胞耗竭的减低强度异基因干细胞移植后，具有高供体源性 T 细胞计数的患者有良好的结局。
Favorable outcomes in patients with high donor-derived T cell count after in vivo T cell-depleted reduced-intensity allogeneic stem cell transplantation.
机构信息
Bone Marrow Transplant Program, Department of Internal Medicine, Massey Cancer Center, Virginia Commonwealth University, Richmond, Virginia 23298-0157, USA.
出版信息
Biol Blood Marrow Transplant. 2012 May;18(5):794-804. doi: 10.1016/j.bbmt.2011.10.011. Epub 2011 Oct 17.
Abstract
Patients with hematologic malignancies were conditioned using a rabbit antithymocyte globulin-based reduced-intensity conditioning regimen for allogeneic stem cell transplantation. Donor-derived CD3(+) cell count (ddCD3), a product of CD3(+) cell chimerism and absolute CD3(+) cell count, when <110/μL at 8 weeks post-stem cell transplantation predicted a high risk of sustained mixed chimerism and relapse. Alternatively, patients with a higher ddCD3 developed graft-versus-host disease more frequently, and when partially chimeric, had higher rates of conversion to full donor chimerism after withdrawal of immunosuppression. Early data from our small cohort of patients indicate that ddCD3 at 8 weeks may be used to guide decisions regarding withdrawal of immunosuppression and administration of donor lymphocyte infusion in partially T cell-depleted reduced-intensity regimens.
摘要
患者患有血液系统恶性肿瘤，接受了基于兔抗胸腺细胞球蛋白的减低强度预处理方案，进行异基因造血干细胞移植。供体来源的 CD3(+)细胞计数（ddCD3）是 CD3(+)细胞嵌合体和绝对 CD3(+)细胞计数的产物，在干细胞移植后 8 周时 <110/μL 预示着持续混合嵌合体和复发的高风险。相反，ddCD3 较高的患者更频繁地发生移植物抗宿主病，当部分嵌合时，在停止免疫抑制后，向完全供体嵌合的转化率更高。我们的小患者队列的早期数据表明，8 周时的 ddCD3 可用于指导决定是否停止免疫抑制以及输注供者淋巴细胞，用于部分 T 细胞耗竭的减低强度方案。
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2
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