摘要
为了探讨全反式维甲酸、活性维生素D3及康力龙联合治疗骨髓增生异常综合征难治性贫血(MDSRA)的疗效及作用机制,治疗组62例采用全反式维甲酸30mg/(m2·d),活性维生素D30.01μg/(kg·d),康力龙0.1mg/(kg·d)治疗,对照组33例采用叶酸及铁剂等治疗。治疗前后检查骨髓及外周血。结果表明:用药8周,治疗组完全缓解(CR)4例,部分缓解(PR)12例,血液学改善(HI)43例(69.35%)。平均随访26.25月出现10例死亡、2例RAEB、1例RAEBT及3例转变为白血病。对照组用药8周无CR,PR3例,HI17例(51.51%)。平均随访16个月出现6例死亡、1例RAEB、1例RAEBT及3例转变为白血病。治疗组3和5年生存率为69.42%和53.72%,对照组为52.23%和31.34%(P=0.016)。治疗组出现副作用程度低。KaplanMeier分析提示,三联治疗、无转变、年龄偏小、无合并症、女性、血红蛋白值90-120g/L、骨髓增生活跃及一系血细胞减少组生存时间长。Cox风险比例模型表明,三联治疗、转变及年龄变量是影响预后的独立因素。结论:三联药物治疗RA疗效高,毒副作用低,治疗有效的机制可能为诱导分化、抗增殖、抗凋亡、抗血管生成、改善营养及调节免疫。
This study was aimed to examine whether a combination of all-trans retinoic acid （ATRA）, 1,25- dihydroxyvitamin D3 and androgen possesses the therapeutic value for the MDS-refractory anemia （MDS-RA）, and to analyze the mechanisms in detail. 62 cases receiving a scheme of combination of ATRA, 1,25-dihydroxyvitamin D3 and androgen （group A） were monitored. The remaining 33 cases （group B） were provided with vitamin supplementation, chalybeate drugs, and one or two of the combination. Bone marrow aspiration and biopsy were performed for collecting the specimens at the baseline and afterwards. The conditions of the patients were monitored by means of weekly complete blood counts and the monthly examination, including toxicity test, physical examination, electrocardiography, and biochemistry panel. The results showed that after treating for 8 weeks in group A, 4 out of 62 patients showed complete remission and 12 patients showed partial remission according to the defined response criteria, and 43 patients （69.35%） showed hematological improvement （ HI ）. The further treatment for 16 out of 62 patients （ 25.81% ）, 13 failures （ 10 deaths, 2 RAEB and 1 RAEB-T） and 3 transformations （ M2 , M3 , M5 ） with a median survival interval of 26.25 months, were observed and interrupted for some reasons. However, partial remission was observed only in 3 patients in group B, and HI amounted to 51.51%. Furthermore, the disease progression was observed in 12 out of 33 patients （36. 36% ） with a median survival interval of 16 months, 9 failures （including 6 deaths, 2 RAEB and 1 RAEB-T） and 3 transformations （M2, M3, M4 ）. The overall ratios of survival for 3 and 5 years in group A, which received the combination, reached to 69.24% and 53.72% respectively, in comparison with 52.23% and 31.34% in the patients of group B （log-rank, P =0.016）. The following requirements, if were met, would be significant for prognosis： the combination regiment, no transformation, children, no complication, female, 90-120 g/L of hemoglobin concentration, normal cellular bone marrow and uni-cytopenias （ P 〈 0. 05 ）. Moreover, Cox regression showed that therapy, transformation and age are all the independent factors （ P 〈 0 . 0 5 ） . It is concluded that the combination of above mentioned 3 drugs may be effective and safe treatment for the patients with MDS-RA. Its relevant mechanisms can be involved in the combination, that elicits a wide range of pharmacological effects, such as differentiation, anti-tumorpromotion, anti-apoptosis, anti-angiogenesis, anti-cachexia and immunoregulation.
出处
《中国实验血液学杂志》
CAS
CSCD
2005年第5期861-866,共6页
Journal of Experimental Hematology
作者简介
通讯作者：张王刚,教授、主任医师、博士生导师,电话：（029）87679457 E-mail.alisantra0351@sina.com
