CAJ | 학술논문

目的探讨白血病患者异基因造血干细胞移植(Allo-HSCT)术后发生股骨头坏死(ONFH)的影响因素及可能机制.方法追踪随访2003年1月至2007年10月接受Allo-HSCT的102例白血病患者,在术后2年内移植物抗宿主病(GvHD)和ONFH的发生情况,并统计患者从初诊到术后2年内甲泼尼龙(MP)的用量.对既发生了急性GvHD(aGvHD)又发生了慢性GvHD(cGvHD)的患者,在MP用量不同阶段定期采用酶联免疫吸附法检测其外周血中破骨细胞分化指标可溶性核转录因子-κB受体活化因子的配体(sRANKL)的水平以及破骨细胞代谢指标抗酒石酸酸性磷酸酶-5b(TRAP-5b)与Ⅰ型胶原蛋白羧基末端交联肽(CTP-Ⅰ)的水平,并分析Allo-HSCT术后ONFH发生的可能影响因素.结果 Allo-HSCT术后2年内,共有7例白血病患者发生了ONFH,发生率为6.9%(7/102),ONFH发生与患者年龄、性别、白血病类型和供者类型无关;ONFH均发生在既有aGvHD又有cGvHD的患者中,ONFH发生率可达21.9%(7/32),明显高于无GvHD、单纯aGvHD和单纯cGvHD患者(P<0.05);在既有aGvHD又有cGvHD的患者中,ONFH阳性患者MP用量(232.7±28.6)mg/kg,明显高于ONFH阴性患者的(115.1 ±16.9)mg/kg(P<0.05).ONFH发生时,患者血浆中sRANKL、TRAP-5b和CTP-Ⅰ的水平明显高于预处理前和术后28 d(P<0.05),且以上指标与MP用量均存在相关性(相关系数分别为0.597、0.664和0.682,P值均<0.05).结论白血病患者Allo-HSCT术后,ONFH的发生与抗GvHD治疗过程中MP用量有关,MP可通过引起患者体内破骨细胞分化及代谢水平增加,导致ONFH的发生.
목적 탐토백혈병환자이기인조혈간세포이식(Allo-HSCT)술후발생고골두배사(ONFH)적영향인소급가능궤제.방법 추종수방2003년1월지2007년10월접수Allo-HSCT적102례백혈병환자,재술후2년내이식물항숙주병(GvHD)화ONFH적발생정황,병통계환자종초진도술후2년내갑발니룡(MP)적용량.대기발생료급성GvHD(aGvHD)우발생료만성GvHD(cGvHD)적환자,재MP용량불동계단정기채용매련면역흡부법검측기외주혈중파골세포분화지표가용성핵전록인자-κB수체활화인자적배체(sRANKL)적수평이급파골세포대사지표항주석산산성린산매-5b(TRAP-5b)여Ⅰ형효원단백최기말단교련태(CTP-Ⅰ)적수평,병분석Allo-HSCT술후ONFH발생적가능영향인소.결과 Allo-HSCT술후2년내,공유7례백혈병환자발생료ONFH,발생솔위6.9%(7/102),ONFH발생여환자년령、성별、백혈병류형화공자류형무관;ONFH균발생재기유aGvHD우유cGvHD적환자중,ONFH발생솔가체21.9%(7/32),명현고우무GvHD、단순aGvHD화단순cGvHD환자(P<0.05);재기유aGvHD우유cGvHD적환자중,ONFH양성환자MP용량(232.7±28.6)mg/kg,명현고우ONFH음성환자적(115.1 ±16.9)mg/kg(P<0.05).ONFH발생시,환자혈장중sRANKL、TRAP-5b화CTP-Ⅰ적수평명현고우예처리전화술후28 d(P<0.05),차이상지표여MP용량균존재상관성(상관계수분별위0.597、0.664화0.682,P치균<0.05).결론 백혈병환자Allo-HSCT술후,ONFH적발생여항GvHD치료과정중MP용량유관,MP가통과인기환자체내파골세포분화급대사수평증가,도치ONFH적발생.
Objective To explore the influencing factors and possible mechanism of osteonecrosis of the femoral head(ONFH)in patients with leukemia after allogeneic hematopoietic stem cell transplantation (Allo-HSCT).Methods One hundred and two patients with leukemia who received Allo-HSCT between January 2003 and October 2007 were evaluated for ONFH and graft-versus-host disease(GvHD)within 2years after transplantation,and the dosage of methylprednisolone(MP)in every patient from the first diagnosis of leukemia to 2 years after Allo-HSCT was calculated.For patients who suffered acute GvHD(aGvHD) and chronic GvHD(cGvHD),the serum leveh of soluble ligand of receptor activator of nuclear factor kappa B (sRANKL)which was index for differentiation of osteoclast(OC),tartrate-resistant acid phosphatase-5b(TRAP-5b)and C-terminal telopeptide of collagen Ⅰ(CTP-Ⅰ)which both were indexes for metabolism of OC were detected by enzyme-linked immunosorbent assay in different stages of MP dosage.According to these results.possible factors for ONFH after Allo-HSCT were analyzed.Results Seven in 102 patients after Allo-HSCT had experienced ONFH within 2 years,the incidence was 6.9%(7/102),which was not related to age,gender,types of leukemia and donor.ONFH mainly developed in patients with aGvHD and cGvHD,and the incidence could be achieved to 21.9%(7/32)which Was much higher than that in patients with no GvHD,merely aGvHD or merely cGvHD(P<0.05).In patients with aGvHD and cGvHD,the average dosage of MP in ONFH(+)was(232.7±28.6)mg/kg which was extremely higher than that in ONFH(-)(115.1±16.9)mg/kg(P<0.05).The serum levels of sRANKL,TRAP-5b and CTP-Ⅰ were also higher when ONFH happened than ahead of pretreatment and 28 days after transplantation(-)(P<0.05),and they were closely related to the dosage of MP(correlation coefficient was 0.597,0.664 and 0.682 respectively,P<0.05).Conclusions After Allo-HSCT,ONFH is related to the dosage of MP in treatment of GvHD.MP may be responsible for enhancement of OC differentiation and metabolism in leukemia patients,and ultimately induced the onset of ONFH.