异基因造血干细胞移植后白血病髓外复发的临床分析

Clinical analysis of extramedullary relapse after allogeneic hematopoietic stem cell transplantation for leukemia

目的 探讨异基因造血干细胞移植（allo-HSCT）后髓外复发的发病机理、危险因素、治疗方法及临床转归.方法 回顾分析164例allo-HSCT受者的临床资料,选择受者性别、年龄、原发病、移植前疾病状态、是否有髓外浸润、预处理方案、供者类型、HLA相合程度、术后移植物抗宿主病（GVHD）发生情况等10个临床参数做单因素分析,对P＜0.1的单因素进行多因素分析.髓外复发的治疗方法包括局部放疗、单纯手术切除,全身化疗、供者淋巴细胞输注和二次移植.结果 164例受者均顺利重建造血功能.术后发生白血病髓外复发9例（5.5%）,髓外复发的中位时间为7.5个月（2.3～42.6个月）;术后发生急性GVHD 94例次（57.3%）,慢性GVHD 83例次（50.6%）.复发后有4例受者死亡.单因素分析表明,受者性别、移植前疾病进展期、移植前髓外浸润、供者类型及术后发生慢性GVHD等因素与白血病髓外复发显著相关（P＜0.1）.经Cox回归多因素分析发现,移植前疾病处于进展期（P＜0.05）、白血病髓外浸润（P＜0.01）及术后发生慢性GVHD（P＜0.01）为alloHSCT后白血病髓外复发的独立危险因素.结论 多种因素参与了髓外复发的发病机理,免疫逃逸可能在其中起主要作用.疾病进展期、移植前伴髓外浸润和慢性GVHD是白血病髓外复发的独立危险因素.白血病髓外复发常伴随骨髓复发,预后较差,因此预防白血病细胞由髓外向髓内扩散对长期存活非常重要.

Objective To investigate the incidence, risk factors, treatment and clinical outcome of extramedullary EM） relapse following allogeneic hematopoietic stem cell transplantation （alloHSCT）, and explore the possible pathogenesis. Methods We retrospectively analyzed the medical records of 164 patients who underwent allogeneic HSCT. The 10 clinical parameters were selected for Cox univariate analysis： gender, age, underlying disease, donor type, disease status at transplant,HLA disparity, acute GVHD, chronic GVHD, EM involvement prior to transplantation and conditioning regimen. Factors that were significant at the 0. 10 level on univariate analysis were evaluated by multivariate analysis using a Cox regression. The therapeutic options for EM relapse included local radiation, surgical removal, chemotherapy, donor lymphocyte infusion （DLI）, second HSCT. Results 164 recipients had sustained engraftment. EM relapse occurred in 9 patients（5.5 %）, with a median time to EM relapse of 7.5 months （2.3 to 42.6 months）. Ninety-fourpatients （57. 3 % ） developed acute GVHD and 83 （50. 6 % ） chronic GVHD respectively. Four patients died of EM relapse. The following factors were associated with an increased risk of EM relapse by univariate analysis： gender, donor type, disease status at transplant, chronic GVHD, EM involvement prior to transplantation. Only advanced stage of the disease （P〈 0. 05）, absence of chronic GVHD （P〈0. 01） and EM involvement prior to transplantation （P〈0. 01） were identified as being significantly associated with the occurrence of EM relapse by multivariate analysis using a Cox regression. Conclusion Many factors may be involved in the pathogenic mechanism of EM relapse,and among them, immune escape might play a major role. Advanced stage of the disease, absence ofchronic GVHD and EM involvement prior to transplantation were independently associated with an increased risk of EM relapse. EM relapse frequently followed by bone marrow involvement has poor prognosis, and therefore, prevention of leukemic cells spreading from EM sites to bone marrow is vital for long-term survival.