Suppr超能文献

尼洛替尼预防对晚期慢性髓性白血病或费城染色体阳性急性淋巴细胞白血病患者异基因干细胞移植后的免疫效应。

Immunological effects of nilotinib prophylaxis after allogeneic stem cell transplantation in patients with advanced chronic myeloid leukemia or philadelphia chromosome-positive acute lymphoblastic leukemia.

作者信息

Varda-Bloom Nira, Danylesko Ivetta, Shouval Roni, Eldror Shiran, Lev Atar, Davidson Jacqueline, Rosenthal Esther, Volchek Yulia, Shem-Tov Noga, Yerushalmi Ronit, Shimoni Avichai, Somech Raz, Nagler Arnon

机构信息

Sheba Medical Center, Ramat-Gan, Israel.

Sackler Faculty of Medicine, Tel-Aviv University, Israel.

出版信息

Oncotarget. 2017 Jan 3;8(1):418-429. doi: 10.18632/oncotarget.13439.

Abstract

Allogeneic stem cell transplantation remains the standard treatment for resistant advanced chronic myeloid leukemia and Philadelphia chromosome-positive acute lymphoblastic leukemia. Relapse is the major cause of treatment failure in both diseases. Post-allo-SCT administration of TKIs could potentially reduce relapse rates, but concerns regarding their effect on immune reconstitution have been raised. We aimed to assess immune functions of 12 advanced CML and Ph+ ALL patients who received post-allo-SCT nilotinib. Lymphocyte subpopulations and their functional activities including T-cell response to mitogens, NK cytotoxic activity and thymic function, determined by quantification of the T cell receptor (TCR) excision circles (TREC) and TCR repertoire, were evaluated at several time points, including pre-nilotib-post-allo-SCT, and up to 365 days on nilotinib treatment. NK cells were the first to recover post allo-SCT. Concomitant to nilotinib administration, total lymphocyte counts and subpopulations gradually increased. CD8 T cells were rapidly reconstituted and continued to increase until day 180 post SCT, while CD4 T cells counts were low until 180-270 days post nilotinib treatment. T-cell response to mitogenic stimulation was not inhibited by nilotinib administration. Thymic activity, measured by TREC copies and surface membrane expression of 24 different TCR Vβ families, was evident in all patients at the end of follow-up after allo-SCT and nilotinib treatment. Finally, nilotinib did not inhibit NK cytotoxic activity. In conclusion, administration of nilotinib post allo-SCT, in attempt to reduce relapse rates or progression of Ph+ ALL and CML, did not jeopardize immune reconstitution or function following transplantation.

摘要

异基因干细胞移植仍然是难治性晚期慢性髓性白血病和费城染色体阳性急性淋巴细胞白血病的标准治疗方法。复发是这两种疾病治疗失败的主要原因。异基因造血干细胞移植(allo-SCT)后给予酪氨酸激酶抑制剂(TKIs)可能会降低复发率,但人们对其对免疫重建的影响表示担忧。我们旨在评估12例接受allo-SCT后使用尼洛替尼的晚期慢性髓性白血病和Ph+急性淋巴细胞白血病患者的免疫功能。在几个时间点评估淋巴细胞亚群及其功能活性,包括T细胞对有丝分裂原的反应、自然杀伤细胞(NK)的细胞毒性活性和胸腺功能,通过定量T细胞受体(TCR)切除环(TREC)和TCR库来确定,时间点包括allo-SCT后尼洛替尼治疗前、后,以及尼洛替尼治疗长达365天。NK细胞是allo-SCT后最先恢复的细胞。在给予尼洛替尼的同时,总淋巴细胞计数和亚群逐渐增加。CD8 T细胞迅速重建并在SCT后180天持续增加,而CD4 T细胞计数在尼洛替尼治疗后180 - 270天一直较低。尼洛替尼的使用并未抑制T细胞对有丝分裂原刺激的反应。通过TREC拷贝数和24个不同TCR Vβ家族的表面膜表达测量的胸腺活性,在allo-SCT和尼洛替尼治疗后的随访结束时在所有患者中均很明显。最后,尼洛替尼并未抑制NK细胞的细胞毒性活性。总之,allo-SCT后给予尼洛替尼以降低Ph+急性淋巴细胞白血病和慢性髓性白血病的复发率或进展,并未损害移植后的免疫重建或功能。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4e33/5352130/f47fdf62527a/oncotarget-08-418-g001.jpg

文献AI研究员

20分钟写一篇综述,助力文献阅读效率提升50倍。

立即体验

用中文搜PubMed

大模型驱动的PubMed中文搜索引擎

马上搜索

文档翻译

学术文献翻译模型,支持多种主流文档格式。

立即体验