Blood:信号通路抑制剂在高危的慢性淋巴细胞白血病中的应用

2018-07-12 MedSci MedSci原创

高风险的慢性淋巴细胞白血病(CLL)的定义是对化疗免疫疗法(CIT)具有临床和/或遗传抵抗(TP53异常)。随着通路抑制剂(PI)的可用性,如激酶抑制剂和BCL2拮抗剂,大大提高了CIT耐药性患者的预后。Peter Dreger等人建议修订高危型CLL的定义,即受TP53异常驱动、PI治疗可缓解。I型高危型CLL,CIT耐药的定义为携带TP53异常、临床上的CIT耐药性疾病,但PI治疗可完全缓解。

高风险的慢性淋巴细胞白血病(CLL)的定义是对化疗免疫疗法(CIT)具有临床和/或遗传抵抗(TP53异常)。随着通路抑制剂(PI)的可用性,如激酶抑制剂和BCL2拮抗剂,大大提高了CIT耐药性患者的预后。

Peter Dreger等人建议修订高危型CLL的定义,即受TP53异常驱动、PI治疗可缓解。I型高危型CLL,CIT耐药的定义为携带TP53异常、临床上的CIT耐药性疾病,但PI治疗可完全缓解。这类疗法在很大程度上是以PI为基础的疗法的领域,而细胞疗法(如同种异体造血细胞移植)仍仅适用于部分相对风险低的患者。

II型高危型CLL,对CIT和PI耐药,其特点是药物治疗的可能性越来越小,这类患者可考虑采用细胞疗法(包括嵌合抗原受体编辑的T细胞)。此外,分子疗法和细胞疗法并不是相互排斥,或可联合应用探索其治疗潜能。

原始出处:

Peter Dreger,et al. High-risk chronic lymphocytic leukemia in the era of pathway inhibitors: Integrating molecular and cellular therapies. Blood  2018  :blood-2018-01-826008;  doi: https://doi.org/10.1182/blood-2018-01-826008

本文系梅斯医学(MedSci)原创编译,转载需授权!

版权声明:
本网站所有内容来源注明为“梅斯医学”或“MedSci原创”的文字、图片和音视频资料,版权均属于梅斯医学所有。非经授权,任何媒体、网站或个人不得转载,授权转载时须注明来源为“梅斯医学”。其它来源的文章系转载文章,或“梅斯号”自媒体发布的文章,仅系出于传递更多信息之目的,本站仅负责审核内容合规,其内容不代表本站立场,本站不负责内容的准确性和版权。如果存在侵权、或不希望被转载的媒体或个人可与我们联系,我们将立即进行删除处理。
在此留言
评论区 (5)
#插入话题
  1. [GetPortalCommentsPageByObjectIdResponse(id=1997903, encodeId=d30f199e90320, content=<a href='/topic/show?id=75ff66001cd' target=_blank style='color:#2F92EE;'>#淋巴细胞白血病#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=30, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=66001, encryptionId=75ff66001cd, topicName=淋巴细胞白血病)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=1be8234, createdName=sunyl07, createdTime=Tue Sep 04 19:50:00 CST 2018, time=2018-09-04, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1851746, encodeId=12de1851e4631, content=<a href='/topic/show?id=f0a254918f0' target=_blank style='color:#2F92EE;'>#抑制剂#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=32, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=54918, encryptionId=f0a254918f0, topicName=抑制剂)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=44a360, createdName=jklm09, createdTime=Fri Mar 01 09:50:00 CST 2019, time=2019-03-01, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=331572, encodeId=1cd13315e2f4, content=学习并分享!!, beContent=null, objectType=article, channel=null, level=null, likeNumber=72, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20200816/e4675a86ea694f12b82202b320dc2654/12f6b900498349e994ce8f516a584d6a.jpg, createdBy=09431951290, createdName=大爰, createdTime=Sat Jul 14 18:32:41 CST 2018, time=2018-07-14, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1302175, encodeId=001913021e537, content=<a href='/topic/show?id=82a6659902c' target=_blank style='color:#2F92EE;'>#淋巴细胞#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=36, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=65990, encryptionId=82a6659902c, topicName=淋巴细胞)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=1e34303, createdName=wetgdt, createdTime=Sat Jul 14 06:50:00 CST 2018, time=2018-07-14, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1539688, encodeId=6cae1539688ae, content=<a href='/topic/show?id=c61a2e315da' target=_blank style='color:#2F92EE;'>#信号通路#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=40, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=27315, encryptionId=c61a2e315da, topicName=信号通路)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=4dfa37, createdName=智者为医08, createdTime=Sat Jul 14 06:50:00 CST 2018, time=2018-07-14, status=1, ipAttribution=)]
  2. [GetPortalCommentsPageByObjectIdResponse(id=1997903, encodeId=d30f199e90320, content=<a href='/topic/show?id=75ff66001cd' target=_blank style='color:#2F92EE;'>#淋巴细胞白血病#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=30, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=66001, encryptionId=75ff66001cd, topicName=淋巴细胞白血病)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=1be8234, createdName=sunyl07, createdTime=Tue Sep 04 19:50:00 CST 2018, time=2018-09-04, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1851746, encodeId=12de1851e4631, content=<a href='/topic/show?id=f0a254918f0' target=_blank style='color:#2F92EE;'>#抑制剂#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=32, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=54918, encryptionId=f0a254918f0, topicName=抑制剂)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=44a360, createdName=jklm09, createdTime=Fri Mar 01 09:50:00 CST 2019, time=2019-03-01, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=331572, encodeId=1cd13315e2f4, content=学习并分享!!, beContent=null, objectType=article, channel=null, level=null, likeNumber=72, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20200816/e4675a86ea694f12b82202b320dc2654/12f6b900498349e994ce8f516a584d6a.jpg, createdBy=09431951290, createdName=大爰, createdTime=Sat Jul 14 18:32:41 CST 2018, time=2018-07-14, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1302175, encodeId=001913021e537, content=<a href='/topic/show?id=82a6659902c' target=_blank style='color:#2F92EE;'>#淋巴细胞#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=36, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=65990, encryptionId=82a6659902c, topicName=淋巴细胞)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=1e34303, createdName=wetgdt, createdTime=Sat Jul 14 06:50:00 CST 2018, time=2018-07-14, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1539688, encodeId=6cae1539688ae, content=<a href='/topic/show?id=c61a2e315da' target=_blank style='color:#2F92EE;'>#信号通路#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=40, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=27315, encryptionId=c61a2e315da, topicName=信号通路)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=4dfa37, createdName=智者为医08, createdTime=Sat Jul 14 06:50:00 CST 2018, time=2018-07-14, status=1, ipAttribution=)]
    2019-03-01 jklm09
  3. [GetPortalCommentsPageByObjectIdResponse(id=1997903, encodeId=d30f199e90320, content=<a href='/topic/show?id=75ff66001cd' target=_blank style='color:#2F92EE;'>#淋巴细胞白血病#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=30, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=66001, encryptionId=75ff66001cd, topicName=淋巴细胞白血病)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=1be8234, createdName=sunyl07, createdTime=Tue Sep 04 19:50:00 CST 2018, time=2018-09-04, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1851746, encodeId=12de1851e4631, content=<a href='/topic/show?id=f0a254918f0' target=_blank style='color:#2F92EE;'>#抑制剂#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=32, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=54918, encryptionId=f0a254918f0, topicName=抑制剂)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=44a360, createdName=jklm09, createdTime=Fri Mar 01 09:50:00 CST 2019, time=2019-03-01, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=331572, encodeId=1cd13315e2f4, content=学习并分享!!, beContent=null, objectType=article, channel=null, level=null, likeNumber=72, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20200816/e4675a86ea694f12b82202b320dc2654/12f6b900498349e994ce8f516a584d6a.jpg, createdBy=09431951290, createdName=大爰, createdTime=Sat Jul 14 18:32:41 CST 2018, time=2018-07-14, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1302175, encodeId=001913021e537, content=<a href='/topic/show?id=82a6659902c' target=_blank style='color:#2F92EE;'>#淋巴细胞#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=36, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=65990, encryptionId=82a6659902c, topicName=淋巴细胞)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=1e34303, createdName=wetgdt, createdTime=Sat Jul 14 06:50:00 CST 2018, time=2018-07-14, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1539688, encodeId=6cae1539688ae, content=<a href='/topic/show?id=c61a2e315da' target=_blank style='color:#2F92EE;'>#信号通路#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=40, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=27315, encryptionId=c61a2e315da, topicName=信号通路)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=4dfa37, createdName=智者为医08, createdTime=Sat Jul 14 06:50:00 CST 2018, time=2018-07-14, status=1, ipAttribution=)]
    2018-07-14 大爰

    学习并分享!!

    0

  4. [GetPortalCommentsPageByObjectIdResponse(id=1997903, encodeId=d30f199e90320, content=<a href='/topic/show?id=75ff66001cd' target=_blank style='color:#2F92EE;'>#淋巴细胞白血病#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=30, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=66001, encryptionId=75ff66001cd, topicName=淋巴细胞白血病)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=1be8234, createdName=sunyl07, createdTime=Tue Sep 04 19:50:00 CST 2018, time=2018-09-04, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1851746, encodeId=12de1851e4631, content=<a href='/topic/show?id=f0a254918f0' target=_blank style='color:#2F92EE;'>#抑制剂#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=32, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=54918, encryptionId=f0a254918f0, topicName=抑制剂)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=44a360, createdName=jklm09, createdTime=Fri Mar 01 09:50:00 CST 2019, time=2019-03-01, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=331572, encodeId=1cd13315e2f4, content=学习并分享!!, beContent=null, objectType=article, channel=null, level=null, likeNumber=72, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20200816/e4675a86ea694f12b82202b320dc2654/12f6b900498349e994ce8f516a584d6a.jpg, createdBy=09431951290, createdName=大爰, createdTime=Sat Jul 14 18:32:41 CST 2018, time=2018-07-14, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1302175, encodeId=001913021e537, content=<a href='/topic/show?id=82a6659902c' target=_blank style='color:#2F92EE;'>#淋巴细胞#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=36, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=65990, encryptionId=82a6659902c, topicName=淋巴细胞)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=1e34303, createdName=wetgdt, createdTime=Sat Jul 14 06:50:00 CST 2018, time=2018-07-14, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1539688, encodeId=6cae1539688ae, content=<a href='/topic/show?id=c61a2e315da' target=_blank style='color:#2F92EE;'>#信号通路#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=40, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=27315, encryptionId=c61a2e315da, topicName=信号通路)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=4dfa37, createdName=智者为医08, createdTime=Sat Jul 14 06:50:00 CST 2018, time=2018-07-14, status=1, ipAttribution=)]
  5. [GetPortalCommentsPageByObjectIdResponse(id=1997903, encodeId=d30f199e90320, content=<a href='/topic/show?id=75ff66001cd' target=_blank style='color:#2F92EE;'>#淋巴细胞白血病#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=30, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=66001, encryptionId=75ff66001cd, topicName=淋巴细胞白血病)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=1be8234, createdName=sunyl07, createdTime=Tue Sep 04 19:50:00 CST 2018, time=2018-09-04, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1851746, encodeId=12de1851e4631, content=<a href='/topic/show?id=f0a254918f0' target=_blank style='color:#2F92EE;'>#抑制剂#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=32, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=54918, encryptionId=f0a254918f0, topicName=抑制剂)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=44a360, createdName=jklm09, createdTime=Fri Mar 01 09:50:00 CST 2019, time=2019-03-01, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=331572, encodeId=1cd13315e2f4, content=学习并分享!!, beContent=null, objectType=article, channel=null, level=null, likeNumber=72, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20200816/e4675a86ea694f12b82202b320dc2654/12f6b900498349e994ce8f516a584d6a.jpg, createdBy=09431951290, createdName=大爰, createdTime=Sat Jul 14 18:32:41 CST 2018, time=2018-07-14, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1302175, encodeId=001913021e537, content=<a href='/topic/show?id=82a6659902c' target=_blank style='color:#2F92EE;'>#淋巴细胞#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=36, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=65990, encryptionId=82a6659902c, topicName=淋巴细胞)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=1e34303, createdName=wetgdt, createdTime=Sat Jul 14 06:50:00 CST 2018, time=2018-07-14, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1539688, encodeId=6cae1539688ae, content=<a href='/topic/show?id=c61a2e315da' target=_blank style='color:#2F92EE;'>#信号通路#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=40, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=27315, encryptionId=c61a2e315da, topicName=信号通路)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=4dfa37, createdName=智者为医08, createdTime=Sat Jul 14 06:50:00 CST 2018, time=2018-07-14, status=1, ipAttribution=)]

相关资讯

NCCN临床实践指南:慢性淋巴细胞白血病/小淋巴细胞淋巴瘤(2018.V5)

2018年3月,美国国家综合癌症网络(NCCN)发布了慢性淋巴细胞白血病/小淋巴细胞淋巴瘤指南2018年第5版,指南主要内容涉及: 指南更新摘要 慢性淋巴细胞白血病/小淋巴细胞淋巴瘤的诊断、检查、分期 虚弱患者的严重合并症 没有17p缺失或Tp53突变的慢性淋巴细胞白血病/小淋巴细胞淋巴瘤 17p缺失或Tp53突变的慢性淋巴细胞白血病/小淋巴细胞淋巴瘤 慢性淋巴细胞白血病/小淋巴细胞淋巴瘤的预后信

Blood:在慢性淋巴细胞白血病中,Wnt5a诱导ROR1招募DOCK2激活Rac1/2,从而增强CLL细胞增殖

中心点:Wnt5a可通过诱导ROR1与DOCK2互作增强Rac1/2的激活。ROR1-DOCK2互作有助于Wnt5a增强的CLL细胞增殖。摘要:酪氨酸激酶样孤儿受体1(ROR1)是表达在慢性淋巴细胞白血病(CLL)细胞上的一种癌胚蛋白,可作为Wnt5a的受体,促进白血病细胞迁移、增殖和存活。研究人员发现Wnt5a可诱导ROR1与DOCK2形成复合物,从而诱导激活Rac1/2;这一效应可可被cirm

《中国慢性淋巴细胞白血病/小淋巴细胞淋巴瘤的诊断与治疗指南(2018年版)》解读

近年,在慢性淋巴细胞白血病(CLL)的基础研究、新的预后标志、诊断标准及治疗等方面取得了巨大进展,为提高我国血液科医师对CLL 诊断、鉴别诊断及规范化治疗水平,中国抗癌协会血液肿瘤专业委员会、中华医学会血液学分会和中国CLL工作组组织相关专家对2015 年版CLL/小淋巴细胞淋巴瘤(SLL)的诊断与治疗指南进行了更新修订。现就2018年版新修订指南进行解读。

中国慢性淋巴细胞白血病 /小淋巴细胞淋巴瘤的诊断与治疗指南(2018年版)

近年,慢性淋巴细胞白血病(CLL)/小淋巴细胞淋巴瘤(SLL)的基础与临床研究,特别是新药治疗方面取得了巨大进展。为提高我国对CLL/SLL诊断、鉴别诊断及规范化治疗水平,中国抗癌协会血液肿瘤专业委员会、中华医学会血液学分会和中国慢性淋巴细胞白血病工作组组织相关专家对2015年版CLL/SLL的诊断与治疗指南进行了更新修订,制订本版指南。

Blood:CD19/CD3双特异性抗体为慢性淋巴细胞白血病患者,特别是依鲁替尼耐药的患者,带来新的希望

Bruton酪氨酸激酶抑制剂依鲁替尼用于慢性淋巴细胞白血病(CLL)患者可获得较高的诱导缓解。但是,仍需要进行辅助治疗强化缓解,以克服耐药性。博纳吐单抗,CD19/CD3的双特异性抗体(bsAb),已获得FDA批准用于治疗复发性/难治性B细胞前体急性淋巴细胞白血病。由于博纳吐单抗半衰期短,仅2.1小时,需持续静脉点滴来保证疗效。Hannah R. Robinson等人开发了一种新型的单链的Fv-F

JCO:中位缓解持续时间33.2个月!Venetoclax使伴del(17p)难治复发CLL患者获持久缓解

伴17号染色体缺失(del[17p])或TP53基因突变的慢性淋巴细胞白血病(CLL)患者预后差,Venetoclax可有效提高该类患者缓解率,但早期临床试验结果尚不能明确Venetoclax应答持久性及安全性等问题。近日,JCO杂志发布了Venetoclax治疗伴del(17p)难治复发CLL患者的最新随访结果,旨在评估Venetoclax应答持久性、安全性及患者微小残留灶(MRD)情况。