抗CD20单克隆抗体联合自体外周血干细胞移植治疗非霍奇金淋巴瘤的临床研究

Clinical study of autologous peripheral blood stem cell transplantation combined with anti-CD20 monoclonal antibody in non-Hodgkin lymphoma

目的探讨抗CD30单克隆抗体（利妥昔单抗，商品名：美罗华）联合自体外周血干细胞移植（APBSCT）治疗B细胞非霍奇金淋巴瘤（NHL）的疗效。方法21例CD30阳性的NHL患者，经过前期治疗，5例达完全缓解（CR），难治性病例为16例，包括11例部分缓解（PR）和5例疾病进展（PD）。在自体造血干细胞动员的第1、8天及预处理的-1、＋7天每天应用利妥昔单抗375mg／m^2。结果移植前疾病达到CR的5例患者，无一例复发；移植前处于PR的11例患者，仅1例在移植后6个月疾病复发，其余均无病生存；移植前处于PD的5例患者，2例无病生存。21例患者中位随访24（1～68）个月，复发、死亡4例（19％），其余17例均无病生存，2年无病生存（EFS）和总生存（OS）率均为81．0％。未观察到利妥昔单抗对采集所得干细胞的质量和数量以及移植后造血恢复有不良影响。结论APBSCT联合利妥昔单抗做体内净化治疗B细胞NHL疗效与移植前状态有关，作为巩固治疗，能使移植前达CR的患者获得长期生存，提高治愈率；作为强化治疗，可提高缓解率，延长PR患者的EFS及OS。利妥昔单抗的加入不影响造血干细胞采集和移植后造血重建。

Objective To evaluate the efficacy of anti-CD20 monoclonal antibody （Rituximab） combined with autologous hematopoietic stem cell transplant （ASCT） in treatment of the patients with B cell non-Hodgkin lymphoma （NHL）. Methods Twenty-one patients with B-cell NHL（CD20 positive） received ASCT with Rituximab at the dose of 375 mg·m^-2·d^-1 on day 1 and day 8 of mobilization, and day -1 and day ＋7 of conditioning regimen. Among the 21 patients receiving chemotherapy before the transplant, five cases achieved complete response （CR）, eleven cases achieved partial remission （PR）, and 5 cases had the progression of disease （PD） after many cycles of chemotherapy. Results The median follow-up was 24 months （1-68 months） in the present study. No relapse occurred among the 5 patients in CR before the transplant. Only one of the 11 PR patients relapsed 6 months post-transplantation. Three of the 5 PD patients died. Four of 21 cases （19 %） were documented as recurrence and death, the other 17 cases remained alive and disease-free. Both 2-year EFS and OS of these cases were 81%. No harmful effect of Rituximab was observed on the quality and quantity of collected stem cells as well as hematopoietic recovery post SCT. Conclusion The efficacy of ASCT with Rituximab in vivo purging in the patients with B-cell NHL was determined mainly by the disease status before transplant. The approach may be used as consolidation therapy to achieve long-term survival and increase the curable rate for patients in CR before transplant, and as intensification therapy to increase the remission rate and prolong the EFS and OS of the patients in PR. Rituximab did not show any adverse effect on collection and reconstitution of hematopoietic stem cells.