利妥昔单抗净化动员B细胞非霍奇金淋巴瘤外周血干细胞的初步研究

Evaluation of rituximab on purgation and mobilization of peripheral blood stem cells in patients with B-cell non-Hodgkin lymphoma

目的观察利妥昔单抗(Rituximab)对B细胞非霍奇金淋巴瘤(NHL)患者外周血干细胞(PBSC)净化动员的作用。方法8例CD2+0B细胞NHL患者,在应用CHOP类化疗±利妥昔单抗4～6疗程诱导/巩固治疗后进行大剂量环磷酰胺(HD-CTX)+粒细胞集落刺激因子(G-CSF)联合利妥昔单抗(375mg·m-2·d-1,-1,+7天)体内净化动员PBSC。观察利妥昔单抗副反应、骨髓抑制期及相关并发症、PBSC采集时间、数量以及采集物肿瘤标志物基因等。结果在外周血干细胞动员过程中仅1例患者发生轻度利妥昔单抗相关的皮疹。PBSC平均采集时间为CTX应用后(11.6±1.0)d,中位采集次数2(1～3)次。采集物平均单个核细胞(MNC)(3.4±1.0)×108/kg,平均CD3+4细胞数(3.6±1.7)×106/kg。5例完成移植患者中3例移植后IgH/TCR转为阴性,1例治疗前后均为阴性,1例早期复发。4例无病生存。结论利妥昔单抗不影响B细胞NHL患者PBSC的动员效果,安全性好,并能加强体内净化作用。

Objective To investigate the effect of rituximab on purging peripheral blood stem cells and mobilization in patients with B-cell non-Hodgkin lymphoma（NHL）. Methods Eight B-cell NHL （stage Ⅲ/Ⅳ）patients received the combination mobilization program composed of high-dose eyclophosphamide （HD-CTX）, granulocyte colony-stimulating factor（G-CSF） and rituximab （375 mg·m^-2·d^-1, on d-1 and d7） after 4 to 6 courses of induction and/or consolidation chemotherapy （CHOP or CHOP-like） ＋ rituximab. Adverse reactions related to rituximab, the period of myelosuppression, complications, the PBSC harvest time and quantity, and the tumor marker genes in harvests were evaluated. Results Only one patient occurred mild erythra in the mobilizing courses. Leukaphereses were started on （11.6±1.0）d after the end of chemotherapy and adequate mononuclear cells （MNC） could be obtained in median of 2（1-3） times harvest procedures. The mean numbers of MNC and CD34^＋, cells harvested separately was （3.4±1.0）×10^8/kg, （3.6±1.7）×10^6/kg. Five patients accomplished auto-peripheral blood stem cells transplantation （APBSCT）, IgH/TCR shifted to negative in three patients, and remained negative in one after APBSCT. Four patents were still in disease free survival; one relapsed at 3 months after APBSCT. Conclusion The addition of rituximab did not compromise the collection efficiency in non-Hodgkin lymphoma patients. Rituximab could potentially purge the graft of occult CD20^＋ tumor cells.