Ayuk Francis, Perez-Simon José A, Shimoni Avichai, Sureda Anna, Zabelina Tatjana, Schwerdtfeger Rainer, Martino Rodrigo, Sayer Herbert Gottfried, Alegre Adrián, Lahuerta Juan-José, Atanackovic Djordje, Wolschke Christine, Nagler Arnon, Zander Axel R, San Miguel Jesús F, Kröger Nicolaus
Dept of Stem cell Transplantation, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, D-20246 Hamburg, Germany.
Haematologica. 2008 Sep;93(9):1343-50. doi: 10.3324/haematol.12665. Epub 2008 Jul 18.
Antithymocyte globulin or human Jurkat T-cell-line-derived antilymphocyte globulin is used in allogeneic stem cell transplantation to induce in vivo T-cell depletion to facilitate engraftment and lower graft-versus-host disease. In vitro studies suggest that antithymocyte globulin, besides causing T-cell depletion, has strong anti-myeloma activity.
We evaluated the anti-myeloma activity of antilymphocyte globulin in a melphalan/fludarabine-based reduced intensity conditioning regimen as well as the incidence of graft-versus-host disease in 138 multiple myeloma patients who underwent allogeneic stem cell transplantation with (n=79) or without (n=59) antilymphocyte globulin.
Leukocyte and platelet engraftment were faster in the group not receiving antilymphocyte globulin (13 vs. 16 days, p<0.001 and 11 vs. 19 days, p< 0.001, respectively). Inclusion of antithymocyte globulin led to a better day 100 overall response rate (93% vs. 78%, p=0.03) and complete response rate (59% vs. 39%, p=0.04), to a lower incidence of both acute grade III/IV graft-versus-host-disease (11% vs. 22%, p=0.10) and chronic graft-versus-host disease (23% vs. 65%, p<0.001) and to a trend to improved event-free survival at 3 years (39% vs. 27%, p=0.5). There was no difference in the estimated cumulative incidence of treatment-related mortality at 1 year between the groups receiving or not antilymphocyte globulin (25% vs. 26%). In a multivariate analysis treatment with antilymphocyte globulin was the only significant factor for achievement of a complete remission (RR:2.57, p=0.02).
Inclusion of antithymocyte globulin in allogeneic stem cell transplantation protocols for patients with multiple myeloma may increase remission rates and at the same time prevent graft-versus-host disease with no increase of relapses.
抗胸腺细胞球蛋白或人Jurkat T细胞系来源的抗淋巴细胞球蛋白用于异基因干细胞移植,以诱导体内T细胞清除,促进植入并降低移植物抗宿主病的发生率。体外研究表明,抗胸腺细胞球蛋白除了导致T细胞清除外,还具有强大的抗骨髓瘤活性。
我们评估了抗淋巴细胞球蛋白在基于美法仑/氟达拉滨的减低强度预处理方案中的抗骨髓瘤活性,以及138例接受或未接受(n = 79和n = 59)抗淋巴细胞球蛋白的异基因干细胞移植的多发性骨髓瘤患者的移植物抗宿主病发生率。
未接受抗淋巴细胞球蛋白的组中白细胞和血小板植入更快(分别为13天对16天,p<0.001;11天对19天,p<0.001)。加入抗胸腺细胞球蛋白导致第100天的总体缓解率更好(93%对78%,p = 0.03)和完全缓解率更高(59%对39%,p = 0.04),急性III/IV级移植物抗宿主病(11%对22%,p = 0.10)和慢性移植物抗宿主病(23%对65%,p<0.001)的发生率更低,并且3年无事件生存率有改善趋势(39%对27%,p = 0.5)。接受或未接受抗淋巴细胞球蛋白的组之间1年时治疗相关死亡率的估计累积发生率无差异(25%对26%)。在多变量分析中,抗淋巴细胞球蛋白治疗是实现完全缓解的唯一显著因素(RR:2.57,p = 0.02)。
在多发性骨髓瘤患者的异基因干细胞移植方案中加入抗胸腺细胞球蛋白可能提高缓解率,同时预防移植物抗宿主病且不增加复发率。