铁过载对重型地中海贫血儿童患者外周血造血干细胞动员效果的影响

The effect of iron overload on the mobilization of peripheral blood hematopoietic stem cells in pediatric patients with thalassemia major

目的研究铁过载对β-重型地中海贫血(TM)儿童患者外周血干细胞(PBSC)动员效果的影响。方法回顾性分析2012年1月—2019年12月本中心218例重型地中海贫血(TM)患者采集外周血造血干细胞(PBSC)的相关数据。采集PBSC前通过检测血清铁蛋白水平及磁共振成像(MRI)T2*方法检测肝脏和心脏的铁负荷,评估TM患者铁过载程度。TM患者注射重组人粒细胞集落刺激因子5d后采用自动单个核细胞分离程序采集PBSC,分析铁过载与动员后外周血白细胞数、单个核细胞数、CD34+细胞数的相关性。结果TM患者的平均年龄为(7.35±3.41)岁。基于铁蛋白水平的铁过载分度,TM患者外周血干细胞相关计数在轻、中、重型三组间未见显著差异。218例TM患者中171例接受了MRI T2*检测。中重度肝脏铁过载组白细胞分离产物WBC计数和单个核细胞计数显著降低(均P<0.05)。171例患者中,152例心脏铁过载MRI T2*水平正常,不同程度的心脏铁过载患者的外周血干细胞计数未见显著差异。结论在TM患者中,中重度肝脏铁过载与PBSC动员效果较差相关。在行PBSC采集术前,通过积极螯合治疗减少肝脏铁过载可能改善PBSC的动员效果,心脏铁过载对PBSC动员的影响需通过进一步扩大样本量进行充分评估。

Objective This study aims to explore the effect of iron overload on the mobilization of peripheral blood stem cells(PBSC)in pediatric patients withβ-thalassemia major(TM).Methods We retrospectively reviewed the records of 218 patients with TM from whom PBSC were collected.Iron overload was based on serum ferritin level,and liver and cardiac iron overload measured by magnetic resonance imaging(MRI)T2*.Patients were treated with recombinant human granulocyte colony stimulating factor for 5 days to mobilize PBSC,and then leukapheresis was performed using a large-volume leukapheresis procedure by automated mononuclear cell(MNC)protocol.Results The mean age of the TM patients was 7.35±3.41 years.Based on the iron overload grading of ferritin level,there was no significant difference in peripheral blood stem cell counts in patients with TM between mild,moderate and severe groups.Of all patients,only 171 received MRI T2*scan.Among 171 patients,35 had normal serum ferritin levels,39 mild liver iron overload,90 intermediate liver iron overload,and 7 severe liver iron overload,intermediate and severe liver iron overload was associated with significantly lower leukapheresis-product WBC count and mononuclear cells count(all,P<0.05);152 had normal cardiac iron levels,9 had mild cardiac iron overload,6 had intermediate cardiac iron overload,and 4 had severe cardiac iron overload,leukapheresis indices were similar among patients with different degrees of cardiac iron overload,which might be due to the small number of patients with cardiac overload.During the 8 years,4 cases received autologous PBSC re-infusion as a rescue for graft failure.Among them,one case died of donor-related acute myeloid leukemia,the remaining 3 had recovered autologous hematopoiesis and survived.Conclusions In patients with TM,intermediate and severe liver iron overload is associated with poorer mobilization of PBSC.Aggressively reducing iron overload via chelation therapy prior to leukapheresis may improve mobilization of PBSC.The effect of cardiac iron overload on PBSC mobilization needs to be fully evaluated further by enough sample size.