Clinical Trial Unit, University Hospital Virgen del Rocío/University of Seville/CSIC/Institute of Biomedicine of Seville, Seville, Spain.
Clinical Unit of Infectious Diseases, Microbiology, and Preventive Medicine, University Hospital Virgen del Rocío/University of Seville/CSIC/Institute of Biomedicine of Seville, Seville, Spain.
BMJ Open. 2020 Jul 20;10(7):e034570. doi: 10.1136/bmjopen-2019-034570.
Haematopoietic stem cell transplantation (HSCT) is a life-saving treatment for a number of haematological diseases. Graft versus host disease (GVHD) is its main complication and hampers survival. There is strong evidence that intestinal microbiota diversity of the recipient may increase the risk of GVHD worsening survival. Antibiotic regimens used during the early phase of the transplant may influence clinical outcomes by reducing intestinal microbiota diversity. Present guidelines of European Conference on Infections in Leukaemia exhort to optimising antibiotic use in haematological patients including HSCT recipients. The present study aims to investigate if, in HSCT recipients, the optimisation of antibacterial use may preserve intestinal microbiota composition reducing the incidence and severity of acute GVHD and improving relevant clinical outcomes.
This is a prospective longitudinal observational study of two cohorts of HSCT recipients: (1) the intervention cohort includes patients treated in centres in which a predefined strategy of antibiotherapy optimisation is implemented, with the objective of optimising and reducing antibiotic administration according to clinical criteria and (2) the control cohort includes patients treated in centres in which a classic permissive strategy of antibiotic prophylaxis and treatment is used. Adult patient receiving a first HSCT as a treatment for any haematological condition are included. Clinical variables are prospectively recorded and up to five faecal samples are collected for microbiota characterisation at prestablished peritransplant time points. Patients are followed since the preconditioning phase throughout 1-year post-transplant and four follow-up visits are scheduled. Faecal microbiota composition and diversity will be compared between both cohorts along with acute GVHD incidence and severity, severe infections rate, mortality and overall and disease-free survival.
The study was approved between 2017 and 2018 by the Ethical Committees of participant centres. Study results will be disseminated through peer-reviewed journals and national and international scientific conferences.
NCT03727113.
造血干细胞移植（HSCT）是治疗许多血液疾病的救命疗法。移植物抗宿主病（GVHD）是其主要并发症，影响生存。有强有力的证据表明，受者肠道微生物多样性可能会增加 GVHD 恶化和生存风险。移植早期使用的抗生素方案可能会通过减少肠道微生物多样性来影响临床结果。目前的欧洲白血病感染会议指南敦促优化血液系统疾病患者（包括 HSCT 受者）的抗生素使用。本研究旨在调查 HSCT 受者中，优化抗菌药物使用是否可以保留肠道微生物群落，降低急性 GVHD 的发生率和严重程度，并改善相关临床结果。
这是一项针对 HSCT 受者的前瞻性纵向观察研究，包括两个队列：（1）干预队列包括在实施抗生素治疗优化策略的中心治疗的患者，其目的是根据临床标准优化和减少抗生素的使用；（2）对照队列包括在中心使用经典的抗生素预防和治疗策略治疗的患者。包括接受首次 HSCT 作为任何血液疾病治疗的成年患者。前瞻性记录临床变量，并在移植前预设时间点采集多达 5 份粪便样本进行微生物群落特征分析。患者从预处理阶段开始随访 1 年移植后，并计划进行 4 次随访。将比较两个队列之间的粪便微生物群落组成和多样性，以及急性 GVHD 的发生率和严重程度、严重感染率、死亡率以及总生存率和无病生存率。
该研究于 2017 年至 2018 年期间获得了参与中心的伦理委员会的批准。研究结果将通过同行评议的期刊以及国家和国际科学会议进行传播。
NCT03727113。
