Wu B Y, Guo K Y, Song C Y, Li D
Hematology Department, Zhujiang Hospital, Guangzhou, People's Republic of China.
Bone Marrow Transplant. 2000 Sep;26(6):691-3. doi: 10.1038/sj.bmt.1702563.
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.
我们没有采用去除供体T细胞的方法，而是在输注前体外使用CTLA4和TJU103（一种据信可阻断CD4与抗原呈递细胞的MHC II分子结合的有机小分子化合物）来阻断供体T淋巴细胞的激活，并使用霉酚酸酯来控制受体淋巴细胞的活性。我们成功治疗了一名接受HLA配型不合移植物且未去除供体T细胞的患者。移植后30天和60天观察到混合嵌合体。STR-PCR显示，在第30天和第60天时，分别有28%和62%的血液单核细胞（MNC）来源于供体。经过三个疗程的供体淋巴细胞输注（DLI）后，当受体中99.7%的MNC来源于供体时，混合嵌合体转变为完全供体嵌合体。观察到与混合嵌合体相关的强大移植物抗白血病（GVL）效应。未发生急性移植物抗宿主病（GVHD），仅在移植后6个月发生了II级慢性GVHD。基于此病例，我们建议：（1）可在不进行供体T细胞去除的情况下，有意跨越HLA屏障建立稳定的混合嵌合体；（2）通过DLI可将混合嵌合体转变为完全供体嵌合体；（3）用这种方法诱导的混合嵌合体可与非常强大的GVL效应相关，并且这些效应可能通过DLI增强，而不会出现严重的GVHD。
