异基因移植后预防性使用利妥昔单抗可降低 B 细胞同种异体免疫反应,慢性移植物抗宿主病发生率低。

Prophylactic rituximab after allogeneic transplantation decreases B-cell alloimmunity with low chronic GVHD incidence.

机构信息

Division of Blood and Marrow Transplantation, Stanford University Medical Center, Stanford, CA 94305, USA.

出版信息

Blood. 2012 Jun 21;119(25):6145-54. doi: 10.1182/blood-2011-12-395970. Epub 2012 May 4.

Abstract

B cells are involved in the pathogenesis of chronic GVHD (cGVHD). We hypothesized that prophylactic anti-B-cell therapy delivered 2 months after transplantation would decrease allogeneic donor B-cell immunity and possibly the incidence of cGVHD. Therefore, in the present study, patients with high-risk chronic lymphocytic leukemia (n = 22) and mantle-cell lymphoma (n = 13) received a total lymphoid irradiation of 80 cGy for 10 days and antithymocyte globulin 1.5 mg/kg/d for 5 days. Rituximab (375 mg/m(2)) was infused weekly on days 56, 63, 70, and 77 after transplantation. The incidence of acute GVHD was 6%. The cumulative incidence of cGVHD was 20%. Nonrelapse mortality was 3%. Rituximab treatment after allogeneic transplantation significantly reduced B-cell allogeneic immunity, with complete prevention of alloreactive H-Y Ab development in male patients with female donors (P = .01). Overall survival and freedom from progression at 4 years for chronic lymphocytic leukemia patients were 73% and 47%, respectively; for mantle-cell lymphoma patients, they were 69% and 53%, respectively.

摘要

B 细胞参与慢性移植物抗宿主病(cGVHD)的发病机制。我们假设在移植后 2 个月给予预防性抗 B 细胞治疗,将减少同种异体供体 B 细胞免疫,并可能降低 cGVHD 的发生率。因此,在本研究中,22 例高危慢性淋巴细胞白血病(CLL)和 13 例套细胞淋巴瘤(MCL)患者接受了 10 天 80cGy 的全身淋巴照射和 5 天 1.5mg/kg/d 的抗胸腺细胞球蛋白治疗。利妥昔单抗(375mg/m2)于移植后第 56、63、70 和 77 天每周输注。急性移植物抗宿主病的发生率为 6%。cGVHD 的累积发生率为 20%。非复发死亡率为 3%。异基因移植后利妥昔单抗治疗显著降低了 B 细胞同种异体免疫,完全预防了女性供体男性患者同种反应性 H-Y Ab 的产生(P=0.01)。慢性淋巴细胞白血病患者的 4 年总生存率和无进展生存率分别为 73%和 47%;套细胞淋巴瘤患者分别为 69%和 53%。

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