CAJ | 학술논문

目的移植后淋巴细胞增殖性疾病(PTLD)是配型不相合造血干细胞移植(HSCT)患者严重并发症之一,本研究拟通过病例对照研究探讨单倍体相合HSCT后发生PTLD的危险因素.方法在1 184例北京大学血液病研究所接受单倍体相合HSCT的患者中选取病理诊断为PTLD的12例患者作为PTLD组,采用巢式病例对照的方法,在同一队列中选取移植年限匹配的患者作为对照组(120例),分析与单倍体相合HSCT后PTLD发生相关的危险因素.结果 PTLD诊断的中位时间为移植后63.5(45 ～ 360)d.两组患者移植前特征、预处理方案及移植物组分的差异均无统计学意义.两组患者移植物抗宿主病和巨细胞病毒感染的比例相仿.移植后30 d,对照组CD19+细胞、CD3+细胞、CD4+细胞和CD8+细胞绝对值及血清IgG和IgM水平均明显高于PTLD组.多因素分析中,移植后30 d外周血CD4+细胞数绝对值低于0.019 9×109/L与PTLD的发生独立相关(OR =6.71,95％CI1.42 ～31.25,P=0.016),低危组(CD4+细胞数绝对值≥0.019 9×109/L,共66例)发生PTLD 2例(3.03％),高危组(CD4+细胞数绝对值＜0.019 9×109/L,共66例)发生PTLD 10例(15.15％)(P=0.015).结论移植后早期免疫重建不佳可能是单倍体相合HSCT患者发生PTLD的危险因素,改善移植后早期的免疫重建可能可以减少PTLD的发生.
목적 이식후림파세포증식성질병(PTLD)시배형불상합조혈간세포이식(HSCT)환자엄중병발증지일,본연구의통과병례대조연구탐토단배체상합HSCT후발생PTLD적위험인소.방법 재1 184례북경대학혈액병연구소접수단배체상합HSCT적환자중선취병리진단위PTLD적12례환자작위PTLD조,채용소식병례대조적방법,재동일대렬중선취이식년한필배적환자작위대조조(120례),분석여단배체상합HSCT후PTLD발생상관적위험인소.결과 PTLD진단적중위시간위이식후63.5(45 ～ 360)d.량조환자이식전특정、예처리방안급이식물조분적차이균무통계학의의.량조환자이식물항숙주병화거세포병독감염적비례상방.이식후30 d,대조조CD19+세포、CD3+세포、CD4+세포화CD8+세포절대치급혈청IgG화IgM수평균명현고우PTLD조.다인소분석중,이식후30 d외주혈CD4+세포수절대치저우0.019 9×109/L여PTLD적발생독립상관(OR =6.71,95％CI1.42 ～31.25,P=0.016),저위조(CD4+세포수절대치≥0.019 9×109/L,공66례)발생PTLD 2례(3.03％),고위조(CD4+세포수절대치＜0.019 9×109/L,공66례)발생PTLD 10례(15.15％)(P=0.015).결론 이식후조기면역중건불가가능시단배체상합HSCT환자발생PTLD적위험인소,개선이식후조기적면역중건가능가이감소PTLD적발생.
Objective Post-transplant lymphoproliferative disorder (PTLD) occurring after allogeneic hematopoietic stem cell transplantation (allo-HSCT) is rare but severe.Risk factors including pre-HSCT exposure variables,conditioning regimens,transplant-related complications,and post-HSCT immune reconstitution were investigated in the development of PTLD after allo-HSCT.Methods A nested case-controlled study was designed.Patients diagnosed with PTLD and controls match for time were identified from a cohort of 1 184 patients who underwent haploidentical HSCT between 2006 and 2012 for hematologic malignancies.Results There were 12 PTLD patients with median time to diagnosis 63.5 d (45-360 d) post-HSCT.The pre-HSCT exposure variables,conditioning regimens and transplant-related complications of the two groups had no statistical difference.Similar rates of graft versus host disease (GVHD) and cytomegalovirus (CMV) infection were seen in both groups.But the absolute count of CD19+ cells,CD3+ cells,CD4+ cells and CD8+ cells at day 30 after HSCT,the serum IgG and IgM were much higher in the control group.In multivariate analysis,absolute count of CD4+ cells lower than 0.019 9 × 109/L (OR=6.71,95％CI 1.42-31.25,P =0.016) at day 30 after HSCT was an independent risk factor for PTLD.Two cases (3.03 ％) of PTLD occurred in the low risk group (absolute count of CD4+ cells ≥ 0.019 9 × 109/L),the other 10 cases (15.15％) in the high risk group (absolute count of CD4+ cells ＜0.019 9 × 109/L).Conclusions Patients with delayed immune reconstitution are at higher risk of developing PTLD after allo-HSCT.Improving the early immune reconstitution may help to decrease the incidence of PTLD after haploidentical HSCT.