白血病患者异基因造血干细胞移植术后股骨头坏死的影响因素

Influencing factors of osteonecrosis of the femoral head after allogeneic hematopoietic stem cell transplantation in patients with leukemia

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.

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.