异基因外周血干细胞移植后早期供者嵌合状态对预后的预测意义

Prognostic significance of early phase donor chimerism after aliogeneic peripheral blood stem cell transplantation

目的 评价清髓性异基因外周血干细胞移植（allo-PBSCT）后早期完全供者嵌合状态（FDC）对患者预后的预测意义。方法 回顾性分析2016年2月至2017年7月行清髓性allo-PBSCT治疗的72例血液病患者临床资料。男44例，女28例，中位年龄36.5（4~59）岁。其中同胞全合供者35例、亲缘单倍型相合供者27例、无关供者10例。采用聚合酶链反应扩增短串联重复序列（PCR-STR）检测移植后1、2、3个月受者骨髓的供者细胞嵌合（DC）率。结果 全部72例患者中位随访462（47~805）d，其中55例存活，2年总体生存（OS）率为（68.9±7.7）%；45例无病存活，2年无病生存（DFS）率为（59.5±6.3）%；16例复发，中位复发时间为移植后157（32~374）d，2年复发率（RR）为（24.1±5.3）%。40例（55.6%）患者发生急性移植物抗宿主病（aGVHD），中位发生时间为移植后35.5（13~90）d；23例（31.9%）发生慢性GVHD（cGVHD），中位发生时间为移植后169（94~475）d。单因素分析显示患者年龄、性别、供受者血型、供受者性别、是否发生aGVHD和cGVHD均不影响OS、DFS率及RR。移植后2个月达到FDC组患者OS、DFS率均高于未达FDC组[OS：（85.2±6.9）%对（66.1±7.7）%，P=0.051；DFS：（76.7±7.7）%对（48.9±8.1）%，P=0.021]，RR低于未达FDC组[（16.6±6.8）%对（30.4±7.8）%，P=0.187]。结论 清髓性allo-PBSCT后早期患者是否达到FDC对移植预后具有重要预测价值，移植后2个月达FDC患者OS及DFS率明显高于未达FDC患者。

Objective To evaluate the prognostic significance of early phase full donor chimerism （FDC） after myeloablative allogeneic peripheral blood stem cell transplantation （allo-PBSCT）. Methods The clinical data of 72 hematological patients received myeloablative allo-PBSCT from Feb. 2016 to Jul. 2017 were analyzed retrospectively. The median age was 36.5 years （range 4-59）, 44 were males and 28 females. Of the donors, there were 35 HLA matched sibling donors, 27 haploidentical donors and 10 unrelated donors. Polymerase chain reaction amplification of short tandem repeat sequence （PCR-STR） was used to detect donor cell chimerism （DC） rate of recipient bone marrow at one, two and three months after transplantation. Results The median follow-up was 462 d （range： 47-805 d）, 55 cases were still alive, and 45 cases were disease-free survival （DFS） at the end of follow-up. The 2-year overall survival （OS） and DFS were （68.9±7.7）% and （59.5±6.3）%, respectively. A number of 16 cases underwent relapses, with 2- year cumulative incidence of （24.1±5.3）%. The median time of recurrence was 157（32-374） d. Forty cases （55.6%） developed acute graft-versus-host diseases （aGVHD）, with median time of 35.5 （13-90） d. Chronic GVHD （cGVHD） occurred in 23 patients （31.9%）, with median time of 169 （94-475） d. Univariate analysis found the following factors were not related to OS, DFS or relapse rate （RR）, including age, sex, blood type and sex of donor-recipient, occurrence of aGVHD and cGVHD. The OS and DFS in cases reached FDC and no FDC at two months after transplantation were （85.2±6.9）% vs （66.1±7.7）% （P = 0.051） and （76.7±7.7）% vs （48.9±8.1）% （P = 0.021）, respectively. The RR rate in FDC group was lower than that in no FDC group [（16.6±6.8）% vs （30.4±7.8）%, P = 0.187, respectively]. Conclusion The present study confirmed the important value for predicting the prognosis with whether or not the patients reached FDC at the early phase after allo-PBSCT. The OS and DFS in cases with FDC at two months after transplantation were significantly higher than those of no FDC patients.