MICA: Microbiota Transplant Prior to Allogeneic Stem Cell Transplant (MAST) study

MICA：同种异体干细胞移植 (MAST) 研究之前的微生物群移植

• 批准号: MR/X004996/1
• 负责人: Julian Marchesi
• 金额: $ 179.89万
• 依托单位: Imperial College London
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2022
• 资助国家: 英国
• 起止时间: 2022 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FX004996%2F1
• 关键词: MICA; Microbiota; Transplant; Prior; Allogeneic

The microbes which inhabit our gut play a pivotal role in our health, influencing the immune system, response of a patient to drugs and progression of many diseases. Blood cancer patients frequently become colonised with (or 'carriers' for) bacteria in different areas of the body (including their gut lining) that are resistant to nearly all the known antibiotics that we have; these bacteria can enter the bloodstream and cause severe infections that are hard to treat. This situation arises because these patients are frequently prescribed antibiotics to control and treat infections, as well as because of the chemotherapy they receive. In healthy individuals, the many health-associated gut microbes we have can protect against colonisation by antibiotic resistant bacteria , but this function is severely compromised in blood cancer patients due to the many courses of antibiotics that they have received during their disease.Since the antibiotics that we have cannot kill these pathogens in the cancer patients, we developed an alternative treatment that transplants the gut microbes from healthy individuals into the intestines of blood cancer patients who are colonised with antibiotic resistant bacteria. When we undertook this procedure, our primary goal was to control the number of antibiotic resistant bacteria. However, the haematologists also unexpectedly noticed that their patients were responding to their bone marrow transplant treatment better than the patients who had not received gut microbes transplantation. We found that the blood cancer patients who had received a gut microbes transplantation were less likely to need further antibiotics during treatment. Furthermore, none of them were admitted to intensive care, they had fewer days in hospital, fewer cases of fever, and better long-term success of their stem cell transplant. These changes in their response to the bone marrow transplant spurred us to consider whether a gut microbes transplantation in patients with leukaemia before they receive their bone marrow transplant will improve the patient's journey during treatment for their cancer.To test this idea further, we will conduct a randomised placebo-controlled clinical trial. We will randomise blood cancer patients to receive either a capsule containing gut microbes from a healthy donor or a placebo capsule before they receive their bone marrow transplant. We will compare the diversity (degree of mixture) of the microbes in their gut, between the two groups over time, as low gut microbe diversity has been shown to predict blood cancer patients having more problems after their stem cell transplant. We will also compare how patients in each group respond to their treatment, any safety issues, and whether any extra treatment or care is required.

居住在我们的肠道中的微生物在我们的健康中起着关键作用，影响了免疫系统，患者对药物的反应以及许多疾病的进展。血液癌患者经常在身体不同区域（包括其肠壁）中被（或“载体”）定殖，这些细菌几乎对我们拥有的几乎所有已知抗生素具有抗药性。这些细菌可以进入血液，并引起严重的感染，难以治疗。之所以出现这种情况，是因为这些患者经常被处方以控制和治疗感染的抗生素，以及他们接受的化学疗法。在健康的个体中，我们拥有的许多与健康相关的肠道微生物可以预防抗生素耐药细菌的定殖，但是由于他们在疾病期间接受了许多抗生素的抗生素，我们无法在癌症患者中杀死癌症，因此，由于他们在其疾病期间接受了许多抗生素，因此，由于他们在疾病期间接受了许多抗生素，因此在血液癌患者中受到严重损害。用抗生素抗性细菌定植的人。当我们进行此过程时，我们的主要目标是控制抗生素耐药细菌的数量。但是，血液学家还意外地注意到，与未接受肠道微生物移植的患者相比，他们的患者对骨髓移植治疗的反应更好。我们发现接受肠道微生物移植的血液癌患者在治疗过程中不需要进一步的抗生素。此外，他们都没有被接受重症监护，他们在医院的日子较少，发烧病例较少，并且干细胞移植的长期成功。它们对骨髓移植的反应发生的这些变化促使我们考虑在接受肠道的肠道微生物在接受骨髓移植之前的肠道微生物移植会改善患者在治疗期间的癌症过程中。进一步测试这一想法，我们将进行随机的安慰剂控制临床试验。我们将随机化血液癌患者在接受骨髓移植之前接收含有健康供体的肠道微生物或安慰剂胶囊的胶囊。我们将比较肠道中微生物在两组之间的多样性（混合程度），因为已经显示出低肠道微生物的多样性可以预测其干细胞移植后血液癌患者有更多问题。我们还将比较每个组中的患者如何应对他们的治疗，任何安全问题以及是否需要任何额外的治疗或护理。