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多发性骨髓瘤是中老年人群常见且不能治愈的一种恶性肿瘤,蛋白酶体抑制剂硼酸盐二肽主要通过作用于NF-κB而影响黏附分子表达、抑制血管生成、促进瘤细胞凋亡、降低IL-6等细胞因子分泌达到选择性杀伤骨髓瘤细胞目的。本研究报道了硼酸盐二肽对2例复发难治性多发性骨髓瘤的临床治疗情况。病例1为多发性骨髓瘤,IgA型,ⅢA期的复发难治性病例,在自体外周血干细胞移植后8个月出现病情复发进展,先后给予多种药物组成的联合化疗方案治疗4个疗程,病情呈侵袭性进展,表现为骨髓中骨髓瘤细胞增加,血浆异常单克隆免疫球蛋白增高和骨骼破坏加重,并出现肋骨浆细胞瘤。给予硼酸盐二肽联合柔红霉素、地塞米松、沙利度胺的VADT方案治疗1个疗程获得显著疗效,表现为血浆IgA由54g/L降至6.6g/L,骨髓异常浆细胞由治疗前40%降至0.6%,患者右侧前上胸壁外侧5cm×6cm骨骼包块在治疗后基本消散;但第2个疗程VADT方案治疗无效并再次出现病情进展。病例2为多发性骨髓瘤,轻链kappa型,ⅢB期的原发难治性患者,先后2个疗程VAD和1疗程MOFP方案化疗无效;在VADT方案治疗1个疗程后即获得显著疗效,尿kappa由24-30g/24h降至1.12g/24h,血肌酐由475.3μmol/L降至124.2μmol/L,β2微球蛋白由1.61mg/dl降至0.64mg/dl;第3疗程后尿kappa定量降至0.088g/24h,β2-MG、LDH和白蛋白水平均在正常范围,获完全缓解。病例1主要不良反应有明显疲乏无力,水样腹泻,四肢指趾端轻微发麻发木,均可耐受,并经对症处理及停用治疗后逐渐消失。病例2的主要并发症为第1疗程第3次用药时硼酸盐二肽剂量增加为1.45mg/m2后出现严重的亚急性左侧肢体偏身运动障碍,发病第2天最为严重,左侧上肢近端肌力1级,远端0级,左下肢2级,2周以后肌力逐渐恢复至正常;本例患者无疲乏、血小板减少等并发症。结论硼酸盐二肽是一个靶向性治疗多发性骨髓瘤的有效药物,但作为一种新药需注意加强不良反应的观察,及时处理可能出现的并发症。
Multiple myeloma is a common malignant tumor which can not be cured in middle-aged and elderly people. The proteasome inhibitor borate dipeptide affects the expression of adhesion molecules, inhibits angiogenesis and promotes the apoptosis of tumor cells mainly through acting on NF- Reduce the secretion of IL-6 and other cytokines to achieve the purpose of selectively killing myeloma cells. This study reported the borate dipeptide in 2 cases of refractory relapsed multiple myeloma clinical treatment. Case 1 was refractory to recurrent multiple myeloma, IgA and ⅢA. Eight months after autologous peripheral blood stem cell transplantation, the disease progression was recurred. A combination of multiple drug regimens was given successively for 4 courses of treatment, The condition was aggressive progress, manifested as increased myeloma cells in the bone marrow, plasma abnormal monoclonal immunoglobulin increased skeletal destruction and aggravated, and rib plasma cell tumor. Given a borate dipeptide combined with daunorubicin, dexamethasone, thalidomide VADT regimen for a course of treatment for a significant effect, the performance of the plasma IgA decreased from 54g / L to 6.6g / L, myelodystrophy cells From 40% before treatment to 0.6%. The 5 cm × 6 cm skeletal mass outside the right anterior chest wall of the right side of the patient basically disappeared after treatment. However, the treatment of the second course of VADT was ineffective and the disease progressed again. Case 2 was multiple myeloma, light chain kappa type, stage Ⅲ B of primary refractory patients, has 2 courses of VAD and 1 courses of MOFP regimen ineffective; in the VADT regimen after a course of treatment to obtain a significant effect, urine Kappa decreased from 24-30g / 24h to 1.12g / 24h, serum creatinine decreased from 475.3μmol / L to 124.2μmol / L, β2 microglobulin decreased from 1.61mg / dl to 0.64mg / dl; After the third course of urine kappa Quantification down to 0.088g / 24h, β2-MG, LDH and albumin levels were in the normal range, was completely relieved. Case 1 The main adverse reactions were obviously tired and weak, watery diarrhea, slight numbness on the toe of extremities, which could be tolerated and gradually disappeared after symptomatic treatment and discontinuation of treatment. Case 2, the main complication of the first course of treatment of the third dose borate dipeptide dose increased to 1.45mg / m2 after serious sub-acute left limb body movement disorders, the incidence of the second day the most serious left Upper body proximal muscle strength 1, distal 0, left lower extremity 2, muscle strength gradually returned to normal after 2 weeks; this patient without fatigue, thrombocytopenia and other complications. Conclusions Borate dipeptide is an effective drug for targeted therapy of multiple myeloma. However, as a new drug, attention should be paid to strengthen the observation of adverse reactions and timely treatment of possible complications.