Fecal Microbiota Transplantation Among Adult Patients With Hematological Malignancies

Официальное название

Manipulation of the Enteral Microbiome by Fecal Microbiota Transplantation Among Adult Patients With Malignant Hematological Diseases

Обзор

In Hungary - in comparison to other member states of the European Union - about 75000 new cases of cancer are diagnosed annually, from which approximately 4500-5000 patients suffer from so-called malignant hematological diseases. This disease group includes various leukemias (blood cancers) and lymphomas (lymph node cancers). Chemotherapy for patients with malignant hematological diseases is particularly difficult to bear, as it affects the entire body, including the "good" gut bacteria living inside, and recovery can take several years. Due to the decrease of the "good" gut bacteria during treatment, patients are more prone to acquiring various difficult-to-treat infections, which can lead to deterioration of quality of life, prolonged hospitalization, and in the worst cases, death. The method outlined in this research plan is called fecal microbiota transplantation, during which stool from a healthy person is introduced into the body of the sick patient. The "good" gut bacteria present in the stool then restore the patient's entire gut flora (the process is somewhat similar to the use of probiotics available on the market, but it is a much more effective method). This research aims to assess the success of fecal microbiota transplantation in adults with malignant hematological diseases over a long-term follow-up period, thus contributing to the restoration of their acceptable quality of life.

Подробное описание

Fecal microbiota transplantation (FMT) is currently a widely accepted method of manipulating enteric microbiome, and is an internationally recommended procedure in the treatment for Clostridioides (formerly Clostridium) difficile (C. difficile) infection. The goal of FMT is to restore physiological gut microbiome through natural competition, by administering a stool graft harvested from a healthy person. FMT not only eliminates C. difficile-induced colitis, but also colonization of multidrug-resistant bacterial/fungal species, and certain types of intestinal epithelial damage occuring in some medical conditions. In recent years due to pleiotropic effects of FMT, scientific interest has turned towards adult patients with malignant hematological diseases, since all of the pathological conditions mentioned earlier occur during clinical care in this population, due to detrimental effects of immuno-chemotherapy. Based on promising preliminary results, FMT could be a successful, easily implementable intervention for these patients in the future.

Therefore, the aim of this study is to perform FMTs in four indication groups among adult patients with malignant hematological diseases treated at South Pest Central Hospital - National Institute of Hematology and Infectious Diseases (Budapest, Hungary), followed by a 180-day follow-up period, during which standardized clinical, laboratory, imaging, and microbiological data are collected. In addition, a high-resolution microbiome analys to monitor microbiological changes of recipient pre-/post-FMT blood and stool samples is planned, in collaboration with Departmental Group of Infectious Diseases and Institute of Medical Microbiology of Semmelweis University (Budapest, Hungary).

This study aims to assess both the bacterial and fungal components of the enteric microbiome in adult patients receiving routine clinical care for malignant hematological diseases, and to explore the potential of manipulating the microbiome through fecal microbiota transplantation (FMT). The hypothesis is that microbiome manipulation with FMT in these patients may induce a successful and sustained response by restoring the physiological intestinal microbiome, a premise that this long-term, comprehensive clinical and microbiological follow-up study seeks to support.

Вмешательства

• Биопрепарат Fecal Microbial Transplantation
  The technical implementation of FMT procedure is consistent with the methodological letter issued by the National Public Health Center of Hungary. FMT is performed via nasogastric tube with suspended fresh stool graft or fecal filtrate, or lyophilised stool capsules, obtained and prepared from a pre-selected stool donor. Following FMT, the patient is observed for 24 hours at our center. The process is supervised and performed by the lead researcher.

Первичные конечные точки

• Disease activity [Срок оценки: On Day 7, Day 30, Day 60 and Day 180, since the intervention, compared to baseline and controls]

Вторичные конечные точки (4)

• Reducibility of applied immunosuppressive pharmacotherapy [Срок оценки: On Day 7, Day 30, Day 60 and Day 180, since the intervention, compared to baseline and controls]
• Reducibility of applied antimicrobial pharmacotherapy [Срок оценки: On Day 7, Day 30, Day 60 and Day 180, since the intervention, compared to baseline and controls]
• Survival [Срок оценки: On Day 7, Day 30, Day 60 and Day 180, since the intervention, compared controls]
• Clinical cure of C. difficile infection [Срок оценки: On Day 7, Day 30, Day 60 and Day 180, since the intervention, compared to baseline and controls]

Критерии участия

Критерии включения

• Adult patients (diagnosis age ≥18 years) with malignant hematological disease treated at our center, and
• Capable of giving written informed consent after decision-making, and
• Documented patient colonization with MDR bacterial or fungal isolates, or
• Active C. difficile infection, or
• Patient has undergone autologous or allogeneic hematopoietic stem cell transplantation, or
• Ongoing corticosteroid-refractory acute gastrointestinal GvHD.

Exclusion criteria (one or more must be met):

• Active bacterial or fungal bloodstream infection requiring antimicrobial therapy, or
• Peripheral blood absolute neutrophil count <0.5 G/l on ≥7 consecutive days before planned FMT with maximum dose of administered G-CSF, or
• Pressor-refractory septic shock, or
• Major gastrointestinal bleeding within 7 consecutive days before planned FMT, or
• Any pathological process inhibiting successful or safe nasogastric tube insertion, or
• Lack of written informed consent.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Нерандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Венгрия · 1 центр

• South Pest Central Hospital, National Institute of Hematology and Infectious Diseases — Budapest

Публикации

• Deeg HJ. How I treat refractory acute GVHD. Blood. 2007 May 15;109(10):4119-26. doi: 10.1182/blood-2006-12-041889. Epub 2007 Jan 18. PMID 17234737
• Pession A, Zama D, Muratore E, Leardini D, Gori D, Guaraldi F, Prete A, Turroni S, Brigidi P, Masetti R. Fecal Microbiota Transplantation in Allogeneic Hematopoietic Stem Cell Transplantation Recipients: A Systematic Review. J Pers Med. 2021 Feb 4;11(2):100. doi: 10.3390/jpm11020100. PMID 33557125
• Kaito S, Toya T, Yoshifuji K, Kurosawa S, Inamoto K, Takeshita K, Suda W, Kakihana K, Honda K, Hattori M, Ohashi K. Fecal microbiota transplantation with frozen capsules for a patient with refractory acute gut graft-versus-host disease. Blood Adv. 2018 Nov 27;2(22):3097-3101. doi: 10.1182/bloodadvances.2018024968. PMID 30446486
• DeFilipp Z, Peled JU, Li S, Mahabamunuge J, Dagher Z, Slingerland AE, Del Rio C, Valles B, Kempner ME, Smith M, Brown J, Dey BR, El-Jawahri A, McAfee SL, Spitzer TR, Ballen KK, Sung AD, Dalton TE, Messina JA, Dettmer K, Liebisch G, Oefner P, Taur Y, Pamer EG, Holler E, Mansour MK, van den Brink MRM, Hohmann E, Jenq RR, Chen YB. Third-party fecal microbiota transplantation following allo-HCT recons PMID 29592876
• Biernat MM, Urbaniak-Kujda D, Dybko J, Kapelko-Slowik K, Prajs I, Wrobel T. Fecal microbiota transplantation in the treatment of intestinal steroid-resistant graft-versus-host disease: two case reports and a review of the literature. J Int Med Res. 2020 Jun;48(6):300060520925693. doi: 10.1177/0300060520925693. PMID 32527171
• Battipaglia G, Malard F, Rubio MT, Ruggeri A, Mamez AC, Brissot E, Giannotti F, Dulery R, Joly AC, Baylatry MT, Kossmann MJ, Tankovic J, Beaugerie L, Sokol H, Mohty M. Fecal microbiota transplantation before or after allogeneic hematopoietic transplantation in patients with hematologic malignancies carrying multidrug-resistance bacteria. Haematologica. 2019 Aug;104(8):1682-1688. doi: 10.3324/haema PMID 30733264
• Cammarota G, Ianiro G, Tilg H, Rajilic-Stojanovic M, Kump P, Satokari R, Sokol H, Arkkila P, Pintus C, Hart A, Segal J, Aloi M, Masucci L, Molinaro A, Scaldaferri F, Gasbarrini G, Lopez-Sanroman A, Link A, de Groot P, de Vos WM, Hogenauer C, Malfertheiner P, Mattila E, Milosavljevic T, Nieuwdorp M, Sanguinetti M, Simren M, Gasbarrini A; European FMT Working Group. European consensus conference on PMID 28087657
• McDonald LC, Gerding DN, Johnson S, Bakken JS, Carroll KC, Coffin SE, Dubberke ER, Garey KW, Gould CV, Kelly C, Loo V, Shaklee Sammons J, Sandora TJ, Wilcox MH. Clinical Practice Guidelines for Clostridium difficile Infection in Adults and Children: 2017 Update by the Infectious Diseases Society of America (IDSA) and Society for Healthcare Epidemiology of America (SHEA). Clin Infect Dis. 2018 Mar PMID 29462280

Идентификаторы

NCT: NCT07172191 · HEMAT-FMT · 15754-3/2023/EÜIG

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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