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减低预处理剂量的异基因造血干细胞移植治疗骨髓增生异常综合征

Allogeneic hematopoietic stem cell transplantation with low intensity preconditioning for patients with myelodysplastic syndromes
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摘要 目的:评估10例骨髓增生异常综合征(MDS)患者进行非清髓异基因造血干细胞移植的效果。方法:10例MDS患者中位年龄44岁,MDS-难治性贫血(RA)1例[国际预后积分系统(IPSS)中危-Ⅰ],MDS-难治性血细胞减少伴有多系增生异常(RCMD)5例(IPSS中危-Ⅰ4例,中危-Ⅱ1例),MDS转变为急性髓系白血病4例(均为IPSS高危)。人类白细胞抗原(HLA)完全相合同胞移植7例,HLA匹配无关供者移植3例。预处理方案以白消安8~10mg/kg、氟达拉滨90~150mg/m2及全身照射2~3Gy为主,移植物抗宿主病(GVHD)预防方案为环孢素、短程甲氨蝶呤和麦考酚酸酯。移植后供受者嵌合体检测采用PCR扩增短串联重复序列方法,对流式细胞仪分选出的T淋巴细胞、自然杀伤(NK)细胞和粒细胞进行动态定量检测。结果:移植后异基因造血干细胞都成功植入,中性粒细胞>0.5×109/L的中位时间为12(10~14)d,血小板>50×109/L的中位时间为13(0~29)d。10例患者中8例发生急性GVHD,其中仅1例患者发生Ⅳ度急性GVHD,其余患者为Ⅰ度。中位随访22(3.6~70)个月,5例发生慢性GVHD。2例患者死亡,均在移植前转变为急性髓系白血病,其余8例患者均无病生存至今,血细胞数恢复正常,中位生存时间为27(15~70)个月,预期5年总生存率为79%。结论:减低预处理剂量的异基因造血干细胞移植是治疗MDS或MDS继发急性髓系白血病的有效方法。移植后需要进行嵌合体的密切监测,根据供受者嵌合比例,尤其是T淋巴细胞嵌合比例给予个体化免疫抑制剂治疗,避免复发。 Objective To evaluate the efficacy of allogeneic hematopoietic stem cell transplantation with low intensity preconditioning in patients with myelodysplastie syndromes (MDS). Methods Ten patients with MDS, including 1 patient with MDS- refractory anemia (RA)[lnternational Prognostic Scoring System (IPSS) intermediate (INT)- Ⅰ riskJ, 5 patients with MDS- refractory cytopenia with muhilineage dysplasia(RCMD)(4 in IPSS INT- Ⅰ risk ,1 in IPSS INT-Ⅱ risk), 4 patients with secondary acute myeloid leukemia(AML) transformed from MDS (all in IPSS high risk), underwent allogneic hematopoietic stem cell transplantation with low intensity preeonditining. Graft source was from related donor in 7 patients and from unrelated donor in 3 patients. The preconditioning regimen included busulfan (8-9 mg/kg), fludarabine (90-150 mg/m^2) and low dose total body irradiation (2-3 Gy). GVHD prophylaxis included eiclosporine, short course of methotrexate and myeophenolate mofetil. Detection of donor-recipient ehimerism was performed by PCR amplication of short tandem repeat sequences. Dynamic quantitative assessment was performed on T-lymphocytes, natural killer cells (NK) and granulocytes separated by flow cytometry. Results All patients were engrafted successfully. The median time of ANC 〉0.5×10^9/L was 12 (10-14) d and PLT〉50×10^9/L was 13 (0-29) d. Of the 10 patients, 8 developed acute GVHD. Only 1 patient developed grade 1W acute GVHD, others were grade I . After 22(3.6-70) months follow up, 5 patients developed chronic GVHD. Two patients AML transformed from MSD died of grade 1Wacute GVHD and relapse, respectively. Eight patients survived till now after 27 (15-70)months follow up. The predicted overall 5-year survival rate was 79%. Conclusions Low intensity preconditioning followed by allogeneic hematopoietie stem cell transplantation from related or unrelated donors is an effective treatment for patients with MDS or AML transformed from MDS. Post-transplantation chimerism monitoring, especially T cell chimerism is important for high risk patients. Immunotherapy based on ehimerism may help to avoid relapse.
出处 《内科理论与实践》 2010年第1期53-56,共4页 Journal of Internal Medicine Concepts & Practice
关键词 骨髓增生异常综合征 异基因 外周血造血干细胞移植 移植物抗宿主病 Myelodysplastie syndrome Allogeneic Hematopoietie stem cell transplantation Graft versus host disease
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参考文献7

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二级参考文献8

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