CAJ | 학술논문

目的总结粒细胞-单核细胞集落刺激因子(GM-CSF)治疗异基因造血干细胞移植(allo-HSCT)后血液系统恶性肿瘤残留疾病两例的经验.方法例1为骨髓增生异常综合征患者,在非血缘HSCT后半年出现骨髓病态造血和不完全嵌合状态,停用免疫抑制剂3周,未出现移植物抗宿主病(GVHD)；例2为B淋巴细胞急性淋巴细胞白血病患者,移植后30d检测到分子水平的残留疾病.两例均皮下注射GM-CSF 300 μg,隔日1次,应用3周.在此过程中观察患者皮疹情况和肝功能,监测外周血淋巴细胞和髓系衍生抑制性细胞亚群、树突状细胞(DC)的变化.结果例1应用GM-CSF 1周后出现皮肤Ⅰ度急性GVHD,3周后出现Ⅱ度(皮肤和肝脏)急性GVHD,停用GM-CSF.治疗1个月时骨髓细胞形态学正常,转为完全供者嵌合状态,给予环孢素A(CsA)、吗替麦考酚酯和甲泼尼龙治疗2周而缓解.例2维持CsA(全血浓度为0.134～0.472 μmol/L)治疗,在使用GM-CSF后第9天,出现Ⅰ度急性GVHD,第11天出现Ⅱ度急性GVHD(皮肤),加用泼尼松30 mg/d,共用5d,其后维持Ⅰ度急性GVHD.第30天复查,为分子生物学缓解.2例治疗前后,未发现淋巴细胞亚群变化,但DC有增加趋势,髓系衍生抑制细胞有减少趋势.结论 GMCSF可用于血液系统恶性肿瘤患者HSCT后残留疾病的治疗.
목적 총결립세포-단핵세포집락자격인자(GM-CSF)치료이기인조혈간세포이식(allo-HSCT)후혈액계통악성종류잔류질병량례적경험.방법 례1위골수증생이상종합정환자,재비혈연HSCT후반년출현골수병태조혈화불완전감합상태,정용면역억제제3주,미출현이식물항숙주병(GVHD)；례2위B림파세포급성림파세포백혈병환자,이식후30d검측도분자수평적잔류질병.량례균피하주사GM-CSF 300 μg,격일1차,응용3주.재차과정중관찰환자피진정황화간공능,감측외주혈림파세포화수계연생억제성세포아군、수돌상세포(DC)적변화.결과 례1응용GM-CSF 1주후출현피부Ⅰ도급성GVHD,3주후출현Ⅱ도(피부화간장)급성GVHD,정용GM-CSF.치료1개월시골수세포형태학정상,전위완전공자감합상태,급여배포소A(CsA)、마체맥고분지화갑발니룡치료2주이완해.례2유지CsA(전혈농도위0.134～0.472 μmol/L)치료,재사용GM-CSF후제9천,출현Ⅰ도급성GVHD,제11천출현Ⅱ도급성GVHD(피부),가용발니송30 mg/d,공용5d,기후유지Ⅰ도급성GVHD.제30천복사,위분자생물학완해.2례치료전후,미발현림파세포아군변화,단DC유증가추세,수계연생억제세포유감소추세.결론 GMCSF가용우혈액계통악성종류환자HSCT후잔류질병적치료.
Objective To evaluate the primary effect of granulocyte-monocyte colony stimulating factor (GM-CSF) as an immunotherapy option for treatment of residual disease after alloHSCT.Methods Immunotherapy was performed on two patients with blood malignancy to treat residual disease after allo-HSCT. The patient one,who was diagnosed as having MDS-RAEB Ⅱ,showed bone marrow displasis and incomplete chimerism 6 months after unrelated donor HSCT.Immunosuppressive drug was withdrawn without induction of graft-versus-host disease (GVHD).The patient two B-ALL demonstrated a residual disease at molecular level 30 days post-transplantation.Both of them were given GMCSF (300 μg) subcutaneously once every two days for totally three weeks.During the whole period,skin itch and rash,liver function,subgroups of lymphocytes,and MDSCs and DCs in peripheral blood were investigated.Results In case one,grade Ⅰ skin acute GVHD (aGVHD) appeared as early as one week after GM-CSF administration,as well as grade Ⅱ (skin and liver) by the end of the third weeks,and GM-CSF injection was withdrawn.One month later since the start of GM-CSF,the patient showed normal bone marrow morphology and full donor type chimerism. Cyclosporine A (CsA), mycophenolate mofetil and methylprednisolone were administered for two weeks to control GVHD.In the other case,grade Ⅰ aGVHD occurred 9 days after GMCSF administration,and whole blood CsA maintained at 0.134-0.472 μmol/L.Prednisone (30mg per day for 5 days) was used to control grade Ⅱ GVHD from the 11th day after GM-CSF,and grade Ⅰ GVHD continued without any intervention.On the 30th day after GM-CSF treatment,bone marrow aspiration showed complete molecular remission.In both of the two cases,no differences in lymphocytic subtypes were revealed before and after GM-CSF administration,while there were trends of increased DC number and decreased MDSCs in peripheral blood.Conclusion The administration of GM-CSF as an immunotherapy option for blood malignancy may contribute to the clearance of residual disease after Allo-HSCT.