自体造血干细胞动员的临床应用进展

Progress in clinical application of autologous hematopoietic stem cell mobilization

自体造血干细胞移植(autologous hematopoietic stem cell transplantation,auto-HSCT)是治疗多种血液疾病和实体瘤的有效手段,其中造血干细胞动员是移植成功的关键。传统的粒细胞集落刺激因子(granulocyte colony-stimulating factor,G-CSF)化学治疗动员常导致动员失败。靶向造血干细胞与基质细胞之间相互作用的CXC族趋化因子受体4(C-XC chemokine receptor type 4,CXCR4)/基质细胞衍生因子-1(stromal cell derived factor,SDF-1)轴的新型动员剂普乐沙福和莫替沙福肽已被批准应用于临床,还有一些处于研究阶段的动员剂如布利沙福、HF51116显示出更好的效果。普乐沙福无论在联合G-CSF或者联合G-CSF+化学治疗中均显著提高了CD34^(+)细胞的动员效率,在“抢先”“按需”“及时”“挽救”应用时有更好的效益/费用比。莫替沙福肽则具有更高的CXCR4结合亲和力和更长的临床活性时间。尽管新型动员剂表现出一定程度的优越性,但成本、安全性和最佳应用策略仍需进一步研究。针对造血干细胞与基质细胞之间相互作用动员剂,如P-选择素、VLA-4(α4β1)抑制剂、CXCR2抑制剂仍处于研究阶段。

Autologous hematopoietic stem cell transplantation(auto-HSCT)is an effective way to treat various malignant hematopoietic diseases and solid tumors,among which stem cell mobilization is the key step.Traditional mobilization agents,such as granulocyte colony-stimulating factor(G-CSF)with or without chemotherapy,often cause a failure in mobilization.New mobilization agents,such as plerixafor and motixafortide,which block the interaction of C-X-C chemokine receptor type 4(CXCR4)/stromal cell derived factor(SDF-1)between hematopoietic stem cells and stromal cells,have been approved for clinical utilization.Meanwhile some mobilization agents in preclinical stage,such as burixafor and HF51116,display encouraging effects.Plerixafor,no matter whether it is combined with G-CSF or with G-CSF plus chemotherapy,mobilizes more CD34^(+)cell from bone marrow to peripheral blood than control.Higher ratio of effect to cost is found when plerixafor is used in condition of“on-demand”,“just-in-time”,“in-advance”.Motesafotide has higher CXCR4 binding affinity and longer clinical activity time than plerixafor does.Although the new mobilization agent has shown a certain degree of superiority,further research is needed on cost,safety,and optimal application strategies.Mobilization agents targeting the interaction between hematopoietic stem cells and stromal cells,such as P-selectin,VLA-4(α4β1,and CXCR2 inhibitors,are still in research.