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Blood:靶向CD19的嵌合抗原受体修饰的T细胞免疫疗法的感染性并发症研究。

2017-10-20 fengxiangxin MedSci原创

Lymphodepletion化疗联合CD19靶向嵌合抗原受体修饰的T(CAR-T)细胞是对难治性或复发性B细胞恶性肿瘤的新型疗法。然而,针对这种疗法的感染性并发症尚未有过系统的研究。

T细胞通过基因改造能够表达嵌合抗原受体,用来识别肿瘤抗原。CD19是一个理想的靶标,因为它在大多数B淋巴恶性细胞表面和正常B淋巴细胞表面表达,而不在其他细胞表面表达。

Lymphodepletion化疗联合CD19靶向嵌合抗原受体修饰的T(CAR-T)细胞是对难治性或复发性B细胞恶性肿瘤的新型疗法。然而,针对这种疗法的感染性并发症尚未有过系统的研究。

在前1/2研究阶段中,研究者评估了133名患者在接受CD19 CAR-T细胞治疗后的0-28天和29-90天两个阶段中的感染事件。通过使用多变量Poisson 回归和Cox 回归分别评估治疗前和治疗后的感染危险因素。该队列包括急性淋巴细胞性白血病患者(ALL,n = 47),慢性淋巴细胞性白血病患者(CLL,n = 24)和非霍奇金淋巴瘤患者(NHL,n = 62)。在CAR-T细胞输注后28天内,133例患者(23%)中有43例发生感染,每100风险日的感染密度为1.19。 29-90天内感染密度较低,为0.67(p = 0.02)。

CAR-T细胞输注后发生第一次感染的中位天数为6天。 6例(5%)发生侵袭性真菌感染,5例(4%)患有发生威胁生命的或致命性感染。

在基线特征的调整模型中,ALL患者,之前有≥4的抗肿瘤方案,并且接受了最高CAR-T细胞剂量(2x107细胞/ kg)的患者在28天内的感染密度较高。在多变量分析中,CAR-T细胞输注后的细胞因子释放综合征(CRS)严重程度是与感染相关的唯一因素。

感染的发生率与在类似患者的抢救性化疗免疫治疗临床试验中的观察结果相当。因此,为了减少严重感染的发生,需要改善治疗方案以减少严重的CRS。

原始出处:

Hill JA, Li D, Hay KA.et al.Infectious complications of CD19-targeted chimeric antigen receptor-modified T cell immunotherapy.Blood. 2017 Oct 16. pii: blood-2017-07-793760. doi: 10.1182/blood-2017-07-793760.

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    2018-07-28 丁鹏鹏
  4. 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createdBy=f59b20519025, createdName=xiaoyeshuang, createdTime=Sun Oct 22 04:22:00 CST 2017, time=2017-10-22, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1626736, encodeId=ffca1626e367c, content=<a href='/topic/show?id=2b104e82656' target=_blank style='color:#2F92EE;'>#嵌合抗原受体#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=36, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=47826, encryptionId=2b104e82656, topicName=嵌合抗原受体)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=77a421060517, createdName=dangious, createdTime=Sun Oct 22 04:22:00 CST 2017, time=2017-10-22, status=1, ipAttribution=)]
    2017-10-22 沙漠浪人

    方向性诊断.治疗方法得当

    0

  5. 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  6. 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    2017-10-22 dingxiaobo
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    2017-10-22 zhangyxzsh
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“自然是如此的奇妙!“——加州大学圣地亚哥分校生物科学系教授Cornelis Murre略带感慨的说道。

Blood:SETD2突变会损害DNA的损伤识别,导致白血病患者对化疗产生耐药性。

SETD2,编码H3K36me3转移酶,其突变常发生于复发性急性淋巴细胞白血病和MLL重组急性白血病患者。SETD2突变,可导致白血病患者对DNA损伤性化疗产生耐药性。

Nat Struct Mol Biol:研究人员发现耐药白血病中的酶的形状变化

儿童研究医院的结构生物学家破译了该酶的结构称为ABL调节其活性,使酶自动开关。理解ABL的调节是很重要的,因为突变型的酶(BCR-ABL)在慢性髓性白血病和其他癌症中过度激活。ABL是白细胞中的一种中枢生长控制开关。酶过度激活刺激突变细胞变为白血病失控生长。

Am J Hematol:强化巩固治疗对老年急性髓性白血病患者有利

2017年10月,发表在《Am J Hematol》的一项由澳大利亚科学家进行的研究,考察了强化巩固治疗对年龄≥60岁的急性髓性白血病(AML)患者的耐受性、安全性和有效性。

Nat Cell Biol:重磅!糖尿病药物的神奇作用,杀死癌细胞

科学家们可能已经找到了一种创新的方法来消灭急性骨髓性白血病中的癌细胞,同时保留并再生健康的红细胞。

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