Accelerated Allogeneic Haemopoietic Engraftment after Preceding Rituximab-Therapy

W. Krüger, T. Kiefer, C. Lotze, Fabian P. Thomsen, C. Hirt, F. Schüler, C. Busemann, G. Dölken
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Abstract

The chimeric monoclonal anti-CD20 antibody rituximab and the graft-versus-leukaemia/lymphoma effect after allogeneic stem cell transplantation have improved therapy of lymphatic malignancies during the last decade. In addition, successful therapy of chronic graft-versus-host disease after stem cell transplantation with rituximab has been published. Other investigators correlated prolonged neutropenia after autologous stem cell transplantation with prior rituximab- therapy. To address the question, if rituximab pre-treatment prior to transplantation diminishes the graft versus lymphoma effect afterwards and can prolong engraftment of allogeneic haemopoiesis, we retrospectively analysed data from 34 patients al- lografted for lymphoid malignancies. 19 patients had received at least one course of rituximab prior to allogeneic stem cell transplantation and 15 did not. Both groups matched very good. Patients with rituximab pre-treatment engrafted with 1 leukocyte/nl significantly faster than patients without prior rituxi- mab therapy (12 days (median, range 1-32) vs. 18 days (median, range 12-31), p<0,005). Engraftment of platelets (PLT) occurred as well faster after rituximab pre-treatment. The differences were significant for all three steps (20PLT/nl: 11,5 days (median, range 1-28) vs. 27 days (median, range 11-54) p<0,001; 50PLT/nl: 16,5 days (median, range 11-37) vs. 42 days (median, range 22-70) p<0,001; 100PLT/nl: 22,5 days (median, range 13-52) vs. 60 days (median, range 25-117) p<0,005). The mechanism leading to faster engraftment remains unclear so far. Preceding therapy with rituximab had no influence on event-free survival, overall survival, or manifestation freedom from graft-versus-host disease (GVHD) after allogeneic stem cell transplantation. Patients with GVHD had a significantly better overall survival (p=0,0001) comparing to patients without. In conclusion, this investigation gives no hint for a suppression of GvH and GvL effects by rituximab administration prior to allogeneic stem cell transplantation. In addition, in contrast to results published for autologous stem cell transplantation, no detrimental effects on establishment of graft haemopoiesis after allogeneic stem cell transplantation by preceding ri- tuximab therapy were found.
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先前的利妥昔单抗治疗后加速同种异体造血植入
嵌合单克隆抗cd20抗体利妥昔单抗和同种异体干细胞移植后的移植物抗白血病/淋巴瘤效应在过去十年中改善了淋巴恶性肿瘤的治疗。此外,利妥昔单抗已成功治疗干细胞移植后的慢性移植物抗宿主病。其他研究者将自体干细胞移植后中性粒细胞减少的延长与先前的利妥昔单抗治疗联系起来。为了解决这个问题,移植前的利妥昔单抗治疗是否会减少移植后的移植物抗淋巴瘤效应,并延长同种异体造血的移植时间,我们回顾性分析了34例淋巴恶性肿瘤全移植物患者的数据。19例患者在同种异体干细胞移植前接受了至少一个疗程的利妥昔单抗治疗,15例患者没有接受。两组都匹配得很好。接受利妥昔单抗治疗的患者植入1个白细胞/ 1的速度明显快于未接受利妥昔单抗治疗的患者(12天(中位数,范围1-32)对18天(中位数,范围12-31),p< 0.005)。利妥昔单抗预处理后,血小板(PLT)的植入也更快。所有三个步骤的差异都是显著的(20PLT/nl: 11.5天(中位数,范围1-28)vs. 27天(中位数,范围11-54)p< 0.001;50PLT/nl: 16.5天(中位数,范围11-37)vs. 42天(中位数,范围22-70)p< 0.001;100PLT/nl: 22.5天(中位数,范围13-52)vs. 60天(中位数,范围25-117)p< 0.005)。导致更快植入的机制至今仍不清楚。先前的利妥昔单抗治疗对同种异体干细胞移植后无事件生存期、总生存期或无移植物抗宿主病(GVHD)表现无影响。与没有GVHD的患者相比,GVHD患者的总生存率显著提高(p= 0.0001)。总之,这项研究没有提示在同种异体干细胞移植前使用利妥昔单抗可以抑制GvH和GvL的作用。此外,与已发表的自体干细胞移植的结果相反,未发现同种异体干细胞移植后接受利妥昔单抗治疗对移植物造血的建立有不利影响。
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