CAJ | 학술논문

目的进一步探讨骨髓增生异常综合征-难治性贫血(MDS-RA)患者采用异基因造血干细胞移植的安全性、有效性、可行性等;联合应用供者来源间充质干细胞(MSC)移植,进一步了解MSC在造血重建和免疫抑制方面的作用;探讨移植过程中供者来源乙肝的有效预防措施.方法 MDS-RA患者选用合适的预处理及移植物抗宿主病(GVHD)预防方案,移植前体外分离、培养、扩增供者来源MSC,供者经粒细胞集落刺激因子(G-CSF)动员后在回输当日采集外周血造血干细胞,造血干细胞回输前4 h先行回输MSC.供者来源乙肝处理:供者在移植前1个月开始抗病毒治疗;受者移植前2个月起予乙肝疫苗接种,移植前1周予高效价乙肝免疫球蛋白应用,移植1个月后起预防性抗病毒药物治疗,全程定期检测受者乙肝病毒表面抗原、e抗体、核心抗原、雅培乙肝表面抗体滴度等指标,根据乙肝表面抗体滴度及时补充高效价乙肝免疫球蛋白.结果移植后+10天患者造血重建,造血重建前未出现严重感染、出血等情况,无急慢性GVHD发生.移植后+30天骨髓细胞学示:各系增生活跃,巨核细胞9个,血小板小簇可见;荧光原位杂交技术(FISH)检测性染色体:XY 47/300.移植后+90天FISH检测:XY 7/300.移植后+60天HBV-DNA外周血和骨髓标本均阴性,HBsAb阳性,HBsAh滴度持续大于100,+60天时达800.患者继续随访中,血象正常,生活质量良好.结论初步证实同胞来源异基因造血干细胞联合MSC移植救治MDS-RA方法可行且安全有效,临床有待更多病例积累.采用乙肝疫苗接种、高效价免疫球蛋白应用联合预防性抗病毒治疗的综合防治措施,有效预防受者感染供者来源乙肝,可供类似病例借鉴.
목적 진일보탐토골수증생이상종합정-난치성빈혈(MDS-RA)환자채용이기인조혈간세포이식적안전성、유효성、가행성등;연합응용공자래원간충질간세포(MSC)이식,진일보료해MSC재조혈중건화면역억제방면적작용;탐토이식과정중공자래원을간적유효예방조시.방법 MDS-RA환자선용합괄적예처리급이식물항숙주병(GVHD)예방방안,이식전체외분리、배양、확증공자래원MSC,공자경립세포집락자격인자(G-CSF)동원후재회수당일채집외주혈조혈간세포,조혈간세포회수전4 h선행회수MSC.공자래원을간처리:공자재이식전1개월개시항병독치료;수자이식전2개월기여을간역묘접충,이식전1주여고효개을간면역구단백응용,이식1개월후기예방성항병독약물치료,전정정기검측수자을간병독표면항원、e항체、핵심항원、아배을간표면항체적도등지표,근거을간표면항체적도급시보충고효개을간면역구단백.결과 이식후+10천환자조혈중건,조혈중건전미출현엄중감염、출혈등정황,무급만성GVHD발생.이식후+30천골수세포학시:각계증생활약,거핵세포9개,혈소판소족가견;형광원위잡교기술(FISH)검측성염색체:XY 47/300.이식후+90천FISH검측:XY 7/300.이식후+60천HBV-DNA외주혈화골수표본균음성,HBsAb양성,HBsAh적도지속대우100,+60천시체800.환자계속수방중,혈상정상,생활질량량호.결론 초보증실동포래원이기인조혈간세포연합MSC이식구치MDS-RA방법가행차안전유효,림상유대경다병례적루.채용을간역묘접충、고효개면역구단백응용연합예방성항병독치료적종합방치조시,유효예방수자감염공자래원을간,가공유사병례차감.
Objective To evaluate the safety, efficiency and feasibility of HLA-identical sibling using culture-expanded mesenchymal stem cells and hematopoietic stem cells in treatment for myelodysplastic syndrome (MDS). Also to investigate for valid preventive measures to avoid the infection of HBV originated from donor. Methods A 46-years-old male patient with myelodysplastic syndrome-refractory anemia (MDSRA) got a cotransplantation of culture-expanded mensenchymal stem cells (MSC) and hematopoietic stem cells (HSCs) from HLA-identical sibling donor (his sister) who was infected by hepatitis B virus (HBV). Some measures were applicated in order to avoid the recipient from getting a HBV infection. The antiviral therapy to the donor was began early at the time 1 month before transplant, and HBV vaccine inoculation was used 2 month before transplant. High titer of anti-hepatis B immunoglobulin was used 1 week before transplant and 1 month after transplant the use of prophylactic anti-hepatis B drug treatment was begun. A non-myeloablative preparative regimen included fludarabine monophosphate (Flu, 120 mg/m2), cyclophosphamide (Cy, 1200 mg/m2)and antithymocyte globulin (ATG, 15 mg/kg) was given to him before culture-expanded mesenchymal stem cell and allogeneic peripheral blood stem cell from his HLA-matched sister. Results The regimen was well tolerated, and hemopoiesis was reconstituted on day 10 after transplant, idiochromosome detected by fluorescent in situ hybridization on day 30 showed XY 47/300 and on day 90 it was 7/300. No evidence of HBV infection was detected on day 60 after transplant. Conclusion The clinical course of this patient indicate that HLA-identical sibling culture-expanded mesenchymal stem cell transplantation combined with non-myeloablative stem cell transplantation can be an effective and safe approach in treatment of MDS.