【作者】 李超；

【导师】 王瑾；

【作者基本信息】 上海交通大学 ， 内科学（血液病学）， 2021， 博士

【摘要】 目的:明确长期含大剂量糖皮质激素的化疗对急性淋巴细胞白血病(ALL)患者骨代谢的影响;分析唑来膦酸用于改善化疗后的急性淋巴细胞白血病患者骨代谢的安全性与有效性。方法:前瞻性收集非移植青少年及成人ALL患者,在诱导和巩固治疗后使用唑来膦酸联合口服碳酸钙和维生素D3,比较唑来膦酸治疗前后患者骨密度及骨转化指标的变化。结果:在唑来膦酸治疗前,48例ALL患者中有7例患者出现骨痛症状,在治疗后6个月,6例骨痛症状消失,1例骨痛症状明显减轻;治疗后1年,全部患者均无骨痛症状。唑来膦酸治疗后,48例患者骨转化指标血清总I型前胶原氨基末端肽(PINP)和I型胶原羧基端肽β特殊序列(β-CTX)显著低于治疗前(p<0.05)。48例患者经过诱导、巩固化疗后,全身各个部位的骨密度和正常人群相比有不同程度的减低,其中大粗隆、Ward’s三角和全髋的骨密度有显著性差异(p<0.05);在使用唑来膦酸联合治疗后6个月,患者该三部位骨密度有明显提高(p<0.05);在治疗后1年,该三部位骨密度与正常人群相比未见显著差异。根据性别分组,在唑来膦酸治疗后6个月,男性的腰椎、股骨颈、大粗隆及全髋部位及女性的股骨颈、大粗隆及全髋部位骨密度有明显提高(p<0.05);治疗后1年,两组患者各部位骨密度与正常人群相比未见明显降低。根据年龄不同分组,在唑来膦酸治疗后6个月,40岁以下患者的大粗隆和全髋部位及40岁及以上患者的全部五个部位骨密度有明显提高(p<0.05);治疗后1年,两组患者各部位骨密度与正常人群相比均未见明显降低。患者出现的不良反应轻微,主要为一过性发热,经过对症治疗均有效改善。结论:唑来膦酸联合钙剂和维生素D3应用方便,可有效改善大剂量糖皮质激素及化疗所引起的ALL患者的骨量减少,提高骨密度,减少骨痛,不良反应轻微,是青少年及成人ALL患者骨量减少的有效治疗方案。更多还原

【Abstract】 PURPOSE: To investigate the effect of long-term chemotherapy with high dose of glucocorticoid on bone metabolism in patients with acute lymphoblastic leukemia and analyze the safety and efficacy of zoledronic acid in improving bone metabolism in patients with acute lymphoblastic leukemia after chemotherapy.METHODS: Zoledronic acid combined with oral calcium carbonate and vitamin D3 was administrated prospectively to non-transplanted adolescent and adult ALL patients after induction and consolidation therapy.Levels of bone mineral density and bone transformation parameters before zoledronic acid treatment and after zoledronic acid treatment were compared.RESULTS: Before zoledronic acid treatment,7 out of 48 ALL patients presented symptoms of bone pain.6 months after treatment,bone pain symptoms in 6 of them disappeared and significantly reduced in the other one patient.One year after treatment,no patient had symptoms of bone pain.The levels of bone transformation indexes,serum total type I procollagen terminal amino peptide(PINP)and β special sequence of type I collagen carboxy terminal peptide(β-CTX),were significantly lower after zoledronic acid treatment(p<0.05).Compared with normal population,the bone mineral density of whole body decreased by various degrees in these 48 patients after induction and consolidation therapy.Among them,significant differences of bone mineral density were observed in the big trochanter,Ward’s triangle and total hip(p<0.05).6 months after zoledronic acid treatment,the bone mineral density of these three parts increased significantly(p<0.05).1 year after zoledronic acid treatment,no significant difference of bone mineral density were found in these three parts compared with the normal population.Grouping by sex,the BMD of lumbar spine,femoral neck,greater trochanter and total hip in male patients and femoral neck and greater trochanter in female patients increased significantly 6 months after zoledronic acid treatment(p< 0.05).1 year after zoledronic acid treatment,no significant decrease of bone mineral density were found in both group compared with the normal population.Grouping by age,the BMD of greater trochanter and total hip in patients under 40 years old and all five parts in patients aged 40 years and older increased significantly 6 months after zoledronic acid treatment(p< 0.05).1 year after zoledronic acid treatment,no significant decrease of bone mineral density were found in both group compared with the normal population.The adverse effects,mainly transient fever,were mild and tolerable after symptomatic treatment.CONCLUSION: Zoledronic acid combined with calcium and Vitamin D3 therapy is convenient and can improve the bone loss of ALL patients caused by high-dose glucocorticoid chemotherapy.It increases bone density and reduce bone pain with tolerable adverse events,which proves to be an effective treatment for adolescent and adult ALL patients with impaired bone mass.更多还原