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.

肠道中的微生物在我们的健康中起着关键作用，影响着免疫系统、病人对药物的反应和许多疾病的进展。血癌患者经常在身体的不同部位（包括他们的肠壁）定植细菌（或“携带者”），这些细菌对几乎所有已知的抗生素都有抗药性；这些细菌可以进入血液，导致难以治疗的严重感染。出现这种情况是因为这些病人经常被开抗生素来控制和治疗感染，也因为他们接受了化疗。在健康个体中，我们拥有的许多与健康相关的肠道微生物可以防止抗生素耐药细菌的定植，但在血癌患者中，由于他们在患病期间接受了许多疗程的抗生素，这种功能严重受损。由于我们现有的抗生素无法杀死癌症患者体内的这些病原体，我们开发了一种替代治疗方法，将健康人的肠道微生物移植到血癌患者的肠道中，这些患者体内有抗生素耐药性细菌。当我们进行这个程序时，我们的主要目标是控制抗生素耐药细菌的数量。然而，血液学家也意外地注意到，他们的患者对骨髓移植治疗的反应比没有接受肠道微生物移植的患者更好。我们发现接受了肠道微生物移植的血癌患者在治疗期间不太可能需要进一步的抗生素治疗。此外，他们都没有被送进重症监护室，他们住院的时间更短，发烧的病例更少，干细胞移植的长期成功率更高。他们对骨髓移植反应的这些变化促使我们考虑在白血病患者接受骨髓移植之前进行肠道微生物移植是否会改善患者的癌症治疗过程。为了进一步验证这一观点，我们将进行一项随机安慰剂对照临床试验。我们将对血癌患者进行随机分组，让他们在接受骨髓移植前接受含有健康捐赠者肠道微生物的胶囊或安慰剂胶囊。随着时间的推移，我们将比较两组患者肠道微生物的多样性（混合程度），因为低肠道微生物多样性已被证明可以预测血癌患者在干细胞移植后会出现更多问题。我们还将比较每组患者对其治疗的反应，任何安全问题，以及是否需要任何额外的治疗或护理。