Page 14 - 2021_06-Haematologica-web

Ferrata Storti Foundation
Haematologica 2021 Volume 106(8):2042-2053
The post-hematopoietic cell transplantation microbiome: relationships with transplant outcome and potential therapeutic targets
Yannouck F. van Lier,1,2 Marcel R.M. van den Brink,3,4 Mette D. Hazenberg1,2,5 and Kate A. Markey3,4
1Department of Hematology, Amsterdam UMC, Amsterdam, the Netherlands; 2Department of Experimental Immunology, Amsterdam Institute for Infection and Immunity (AII), Cancer Center Amsterdam, Amsterdam UMC, Amsterdam, the Netherlands; 3Adult Bone Marrow Transplantation Service, Department of Medicine, Memorial Sloan Kettering Cancer
4
Center, New York, NY, USA; Department of Medicine, Weill Cornell Medical College, New
York, NY, USA and 5Department of Hematopoiesis, Sanquin Research, Amsterdam, the Netherlands
ABSTRACT
Microbiota injury occurs in many patients undergoing allogeneic hematopoietic cell transplantation, likely as a consequence of conditioning regimens involving chemo- and radiotherapy, the widespread use of both prophylactic and therapeutic antibiotics, and pro- found dietary changes during the peri-transplant period. Peri-transplant dysbiosis is characterized by a decrease in bacterial diversity, loss of com- mensal bacteria and single-taxon domination (e.g., with Enterococcal strains). Clinically, deviation of the post-transplant microbiota from a nor- mal, high-diversity, healthy state has been associated with increased risk of bacteremia, development of graft-versus-host disease and decreases in overall survival. A number of recent clinical trials have attempted to target the microbiota in allogeneic hematopoietic cell transplantation patients via dietary interventions, selection of therapeutic antibiotics, administra- tion of pre- or pro-biotics, or by performing fecal microbiota transplanta- tion. These strategies have yielded promising results but the mechanisms by which these interventions influence transplant-related complications remain largely unknown. In this review we summarize the current approaches to targeting the microbiota, discuss potential underlying mechanisms and highlight the key outstanding areas that require further investigation in order to advance microbiota-targeting therapies.
Introduction
Allogeneic hematopoietic cell transplantation (HCT) is the oldest form of cellu- lar therapy for patients with hematologic malignancies, and utilizes stem cell-con- taining grafts from carefully selected donors to invoke immunological anti-malig- nancy effects. This procedure remains high risk for patients, as transplantation- related complications, such as infection and graft-versus-host disease (GvHD), are causes of high morbidity and mortality among allogeneic HCT recipients.1,2 The incidence of acute GvHD in human leukocyte antigen-matched donors remains 30-35%.3 The role of the microbiome in transplant-related complications has been a point of investigation in the field for decades, but advances in sequencing tech- nology and our capacity to study the function of intestinal microbial communities have accelerated this interest in recent years. Approaches to conserve or recover a healthy microbiome in transplant patients are increasingly being used in experi- mental settings with the goal of improving overall transplant outcome.
Pre-transplant conditioning regimens expose the gastrointestinal tract to high doses of chemo- and radiotherapy, resulting in loss of integrity of the intestinal epithelium and inflammatory damage which often results in mucositis.4 Clinical manifestations of mucositis include mouth sores, pain during eating or swallowing, nausea, intestinal cramping, bloating and diarrhea, which commonly minimize a patient’s oral dietary intake. Mucositis is also thought to increase the risk of micro-
Correspondence:
KATE MARKEY
markeyk@mskcc.org
Received: January 11, 2021. Accepted: April 1, 2021. Pre-published: April 22, 2021.
https://doi.org/10.3324/haematol.2020.270835
©2021 Ferrata Storti Foundation
Material published in Haematologica is covered by copyright. All rights are reserved to the Ferrata Storti Foundation. Use of published material is allowed under the following terms and conditions: https://creativecommons.org/licenses/by-nc/4.0/legalcode. Copies of published material are allowed for personal or inter- nal use. Sharing published material for non-commercial pur- poses is subject to the following conditions: https://creativecommons.org/licenses/by-nc/4.0/legalcode, sect. 3. Reproducing and sharing published material for com- mercial purposes is not allowed without permission in writing from the publisher.
2042
haematologica | 2021; 106(8)
REVIEW ARTICLE