文章：

阻断VLA4可使白血病和骨髓瘤肿瘤细胞在骨髓微环境中对CD3重定向敏感

A chemogenomic approach to identify personalized therapy for patients with relapse or refractory acute myeloid leukemia: results of a prospective feasibility study

原文发布日期：2020-06-03

DOI: 10.1038/s41408-020-0330-5

类型: Article

开放获取: 是

英文摘要：

Targeted next-generation sequencing (tNGS) and ex vivo drug sensitivity/resistance profiling (DSRP) have laid foundations defining the functional genomic landscape of acute myeloid leukemia (AML) and premises of personalized medicine to guide treatment options for patients with aggressive and/or chemorefractory hematological malignancies. Here, we have assessed the feasibility of a tailored treatment strategy (TTS) guided by systematic parallel ex vivo DSRP and tNGS for patients with relapsed/refractory AML (number NCT02619071). A TTS issued by an institutional personalized committee could be achieved for 47/55 included patients (85%), 5 based on tNGS only, 6 on DSRP only, while 36 could be proposed on the basis of both, yielding more options and a better rationale. The TSS was available in <21 days for 28 patients (58.3%). On average, 3 to 4 potentially active drugs were selected per patient with only five patient samples being resistant to the entire drug panel. Seventeen patients received a TTS-guided treatment, resulting in four complete remissions, one partial remission, and five decreased peripheral blast counts. Our results show that chemogenomic combining tNGS with DSRP to determine a TTS is a promising approach to propose patient-specific treatment options within 21 days.
 

摘要翻译： 

靶向新一代测序（tNGS）与离体药物敏感性/耐药性分析（DSRP）为界定急性髓系白血病（AML）的功能基因组学图谱奠定了基础，并为个性化医疗提供了前提，以指导侵袭性和/或化疗耐药性血液恶性肿瘤患者的治疗选择。本研究通过系统性并行离体DSRP与tNGS指导，评估了针对复发/难治性AML患者实施定制治疗策略（TTS）的可行性（编号NCT02619071）。在纳入的55例患者中，机构个性化医疗委员会提出的TTS方案在47例（85%）中得以实现——其中5例仅基于tNGS，6例仅基于DSRP，而36例可结合两者提出方案，从而提供更多选择及更充分依据。58.3%的患者（28例）在21天内获得了TTS方案。平均每位患者筛选出3-4种潜在活性药物，仅5例患者样本对全部药物组合耐药。17例患者接受了TTS指导的治疗，实现4例完全缓解、1例部分缓解及5例外周血原始细胞计数下降。我们的研究结果表明，结合tNGS与DSRP的化学基因组学方法可在21天内确定TTS，是一种为患者提供个体化治疗方案的可行策略。

原文链接：

A chemogenomic approach to identify personalized therapy for patients with relapse or refractory acute myeloid leukemia: results of a prospective feasibility study