骨髓巨核细胞变化与凝血象测定在预示APL 复发中意义的研究工作报告

骨髓巨核细胞变化与凝血象测定在预示APL 复发中意义的研究工作报告 骨髓巨核细胞变化与凝血象测定在预示APL 复发中意义的研究工作报告 吉林市医院 夏文春 董德华 如何预防急性早幼粒细胞白血病(APL)复发，降低其死亡率，关键是早诊断早治疗。近年来由于维甲酸诱导分化，亚砷酸促凋亡及配合化疗使诱导缓解率，治愈率逐年提高。如何早期发现病人的复发倾向，预防复发已成为关键之重。APL复发后再治疗其疗效及预后相对较差，死亡率增加。骨髓巨核细胞变化与凝血 象测定在预示急性早幼粒细胞白血病(APL)复发中的研究方面，目前国内还没有相关报道。 巨核细胞系统在化疗过程中是骨髓中最敏感的系统，有报道在急性白血病初治阶段骨髓巨核细胞数量减少,治疗缓解后巨核细胞数量正常或增加。而超高巨核细胞同时伴有形态异常是否预示急性早幼粒细胞白血病的复发，在此阶段凝血机制又是怎样的，尚未见研究。 我们在临床中发现一部分(APL)患者骨髓缓解后，在巩固强化过程中出现骨髓聚核细胞超高，伴有spot welding, spot welding fittings mat must be placed firmly before, to avoid forced groups to arise, additional stress caused by crack. (5) the Groove position welds and welding the same welding process should be adopted, by qualified Welders and welding. Tack weld should be evenly distributed, there is generally no less than 2-3, length should be to 10-15mm, uniform distribution, wall thickness of no more than 2/3. (6) the tack should ensure good penetration and fusion, and free of porosity, slag and other defects. (7) to ensure the bottom bead molding well to reduce stress concentration, tack should be a smooth transition to the base metal and welds polished at both ends should be generated. (8) unless the process or inspection required-welded, but each seam continuous welding finish, otherwise again before welding, to preheat the weld. (9) the welding arc scraped surface is strictly prohibited, without any introduction arc welding on the surface. (10) should ensure that the arc and arc welding of quality, arc should fill crater, multi-pass welding joint should be staggered. (11) Tig welding should be ventilated in advance, expired after welding should be delayed, and should ensure that the welding in the welding process melts to get effective protection of argon gas. (12) when using the multi-pass welding, weld before should be cleaned, after making sure that no defects, and again the next. (13) the weld should be a smooth transition to the base metal and weld both ends ground into slope. (14) card with the welding, the material should be identical to the base metal, and at the time of demolition cards should not damage materials and residues in the welding scar on the base metal polished fixed flush to the base metal. (15) the finished weld, weld 不同程度的病态改变，此时骨髓中早幼粒细胞<5%，骨髓提示临床缓解。随后2~4周骨髓聚核细胞逐渐下降，早幼粒细胞增多，白血病复发。鉴于此，我们在骨髓巨核细胞超高阶段，做凝血象检查，发现凝血时间亦有不同程度的延长，骨髓巨核细胞及凝血象的改变APL复发是否有一定的相关值得探讨。近10年来，我们对39例APL缓解的患者，在巩固强化阶段动态观察骨髓及凝血象变化，其中20例有相关异常，发现骨髓巨核细胞及凝血象改变后复发病例与骨髓巨核细胞及凝血象无改变复发病例比较有显著差异。 资料与方法 临床资料:39例为我市市医院10年来住院患者，其中男18例，女21例，发病年龄12~65岁，平均36.2岁，病程7~124个月，平均54.3个月。 观察方法:在巩固强化阶段每7~14天采集骨髓，常规涂片，瑞士染色，根据骨髓面积进行标准化处理，即在1.5cm×3.0cm(标准面积)范围计算分类巨核细胞，正常值7~35个/单位面积。采用上海太阳生物技术公司试剂，用凝固法测定凝血酶时间(TT)正常值10~16秒;凝血酶原时间(PT)正常值:11~15秒;采用鞣花酸法测定部分凝血活酶时间(APTT)正常值:23~35秒。 spot welding, spot welding fittings mat must be placed firmly before, to avoid forced groups to arise, additional stress caused by crack. (5) the Groove position welds and welding the same welding process should be adopted, by qualified Welders and welding. Tack weld should be evenly distributed, there is generally no less than 2-3, length should be to 10-15mm, uniform distribution, wall thickness of no more than 2/3. (6) the tack should ensure good penetration and fusion, and free of porosity, slag and other defects. (7) to ensure the bottom bead molding well to reduce stress concentration, tack should be a smooth transition to the base metal and welds polished at both ends should be generated. (8) unless the process or inspection required-welded, but each seam continuous welding finish, otherwise again before welding, to preheat the weld. (9) the welding arc scraped surface is strictly prohibited, without any introduction arc welding on the surface. (10) should ensure that the arc and arc welding of quality, arc should fill crater, multi-pass welding joint should be staggered. (11) Tig welding should be ventilated in advance, expired after welding should be delayed, and should ensure that the welding in the welding process melts to get effective protection of argon gas. (12) when using the multi-pass welding, weld before should be cleaned, after making sure that no defects, and again the next. (13) the weld should be a smooth transition to the base metal and weld both ends ground into slope. (14) card with the welding, the material should be identical to the base metal, and at the time of demolition cards should not damage materials and residues in the welding scar on the base metal polished fixed flush to the base metal. (15) the finished weld, weld 判断标准:?巨核细胞的数量:超高值?100个/单位面积;?病态巨核细胞;小巨核，单圆核，多圆核，幼巨核及血小板成堆现象;?TT>16秒，PT>15秒，APTT>35秒。 巨核细胞的生成受多种因素影响，在急性白血病化疗过程中，巨核细胞系统是骨髓三系中最敏感的系统。通过我们对39例完全缓解的APL的骨髓观察， 其中20例伴有超高巨核细胞，2--4周后，18例复发，说明巨核细胞在预示APT复发中的敏感性。有研究证实APL复发前其骨髓、骨髓活检标本的巨核细胞、微血管密度较正常人显著增加。微血管密度增加导致了血管内皮细胞生长因子(VEGF)的过度分泌。研究证明，VEGF通过自分泌和旁分泌途径可介导血液系统肿瘤的生长。此时，白血病细胞尚未增殖，对巨核系祖细胞集落形成未能抑制。因此，在临床中APL复发前可看到短期内异常超高的巨核细胞。随着骨髓早幼粒细胞的增多，对巨核系祖细胞抑制活性的增加，巨核细胞开始下降，白血病复发。说明此抑制活性与白血病细胞产生有关。 病态巨核细胞的出现，提示APT患者虽已达缓解，spot welding, spot welding fittings mat must be placed firmly before, to avoid forced groups to arise, additional stress caused by crack. (5) the Groove position welds and welding the same welding process should be adopted, by qualified Welders and welding. Tack weld should be evenly distributed, there is generally no less than 2-3, length should be to 10-15mm, uniform distribution, wall thickness of no more than 2/3. (6) the tack should ensure good penetration and fusion, and free of porosity, slag and other defects. (7) to ensure the bottom bead molding well to reduce stress concentration, tack should be a smooth transition to the base metal and welds polished at both ends should be generated. (8) unless the process or inspection required-welded, but each seam continuous welding finish, otherwise again before welding, to preheat the weld. (9) the welding arc scraped surface is strictly prohibited, without any introduction arc welding on the surface. (10) should ensure that the arc and arc welding of quality, arc should fill crater, multi-pass welding joint should be staggered. (11) Tig welding should be ventilated in advance, expired after welding should be delayed, and should ensure that the welding in the welding process melts to get effective protection of argon gas. (12) when using the multi-pass welding, weld before should be cleaned, after making sure that no defects, and again the next. (13) the weld should be a smooth transition to the base metal and weld both ends ground into slope. (14) card with the welding, the material should be identical to the base metal, and at the time of demolition cards should not damage materials and residues in the welding scar on the base metal polished fixed flush to the base metal. (15) the finished weld, weld 但由于化疗药物的影响，免疫机能下降以及残余白血病细胞存在等因素，均会导致巨核细胞生成异常，出现质的改变。本组APL在复发前骨髓巨核细胞异常超高但血小板正常或减少，说明伴有病态的超高巨核细胞不能形成正常血小板。无法参与止血功能。这是导致凝血时间延长的一方面原因;另一方面由于血管内皮细胞生长因子(VEGF)的过度分泌，释放大量的细胞组织因子(TF)入血，而细胞组织因子(TF)又是APL的主要促凝物质，该因子的增多可导致凝血系统激活，纤溶亢进，凝血时间延长。 目前国内尚没有预测APL复发的研究报道，我们通过观察，在临床缓解的APL中，骨髓巨核细胞及凝血象有改变者复发率达90%。骨髓巨核细胞、凝血象正常者，复发率仅占10.5%，两者相比有显著差异。说明骨髓巨核细胞及凝血象的改变完全可以作为预示APL复发的一个观察指标。该方法简单易行，适合于基层医院，便于临床医生掌握，值得推广应用。 在本项研究工作中，吉林市医院血液科主任、主任医师夏文春为该项目的负责人，负责该项目的研究方向，整体设计和实施。董德华主管护师负责本项目的资料查阅及文字整理工作。陈宇辉、吴传印、盖秀spot welding, spot welding fittings mat must be placed firmly before, to avoid forced groups to arise, additional stress caused by crack. (5) the Groove position welds and welding the same welding process should be adopted, by qualified Welders and welding. Tack weld should be evenly distributed, there is generally no less than 2-3, length should be to 10-15mm, uniform distribution, wall thickness of no more than 2/3. (6) the tack should ensure good penetration and fusion, and free of porosity, slag and other defects. (7) to ensure the bottom bead molding well to reduce stress concentration, tack should be a smooth transition to the base metal and welds polished at both ends should be generated. (8) unless the process or inspection required-welded, but each seam continuous welding finish, otherwise again before welding, to preheat the weld. (9) the welding arc scraped surface is strictly prohibited, without any introduction arc welding on the surface. (10) should ensure that the arc and arc welding of quality, arc should fill crater, multi-pass welding joint should be staggered. (11) Tig welding should be ventilated in advance, expired after welding should be delayed, and should ensure that the welding in the welding process melts to get effective protection of argon gas. (12) when using the multi-pass welding, weld before should be cleaned, after making sure that no defects, and again the next. (13) the weld should be a smooth transition to the base metal and weld both ends ground into slope. (14) card with the welding, the material should be identical to the base metal, and at the time of demolition cards should not damage materials and residues in the welding scar on the base metal polished fixed flush to the base metal. (15) the finished weld, weld 英、沈虹、王清霞、田杏、何红、师尚军等负责项目的临床观察等。 在此感谢中国人民解放军301医院对本项研究的技术支持，同时也感谢吉化集团总医院、北华大学附属医院、吉林市中心医院、吉林医药学院附属医院、中国人民解放军二二二医院在本项目临床验证工作中的大力支持。 spot welding, spot welding fittings mat must be placed firmly before, to avoid forced groups to arise, additional stress caused by crack. (5) the Groove position welds and welding the same welding process should be adopted, by qualified Welders and welding. Tack weld should be evenly distributed, there is generally no less than 2-3, length should be to 10-15mm, uniform distribution, wall thickness of no more than 2/3. (6) the tack should ensure good penetration and fusion, and free of porosity, slag and other defects. (7) to ensure the bottom bead molding well to reduce stress concentration, tack should be a smooth transition to the base metal and welds polished at both ends should be generated. (8) unless the process or inspection required-welded, but each seam continuous welding finish, otherwise again before welding, to preheat the weld. (9) the welding arc scraped surface is strictly prohibited, without any introduction arc welding on the surface. (10) should ensure that the arc and arc welding of quality, arc should fill crater, multi-pass welding joint should be staggered. (11) Tig welding should be ventilated in advance, expired after welding should be delayed, and should ensure that the welding in the welding process melts to get effective protection of argon gas. (12) when using the multi-pass welding, weld before should be cleaned, after making sure that no defects, and again the next. (13) the weld should be a smooth transition to the base metal and weld both ends ground into slope. (14) card with the welding, the material should be identical to the base metal, and at the time of demolition cards should not damage materials and residues in the welding scar on the base metal polished fixed flush to the base metal. (15) the finished weld, weld