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World J Stem Cells. Oct 26, 2020; 12(10): 1113-1123
Published online Oct 26, 2020. doi: 10.4252/wjsc.v12.i10.1113
Medical, ethical, and legal aspects of hematopoietic stem cell transplantation for Crohn’s disease in Brazil
Milton Artur Ruiz, Roberto Luiz Kaiser Junior, Lilian Piron-Ruiz, Priscila Samara Saran, Lilian Castiglioni, Luiz Gustavo de Quadros, Tainara Souza Pinho, Richard K Burt
Milton Artur Ruiz, Department of Bone Marrow Transplant, Beneficência Portuguesa Hospital, São José do Rio Preto 15090 470, Brazil
Roberto Luiz Kaiser Junior, Department of Proctology, Beneficencia Portuguesa Hospital, São José do Rio Preto 15090 470, Brazil
Lilian Piron-Ruiz, Priscila Samara Saran, Tainara Souza Pinho, Department of Bone Marrow Transplantation, Beneficência Portuguesa Hospital, São José do Rio Preto 15090 470, Brazil
Lilian Castiglioni, Genetics and Molecular Biology, FAMERP- Faculdade de Medicina de São José do Rio Preto, São José do Rio Preto 15090 470 Brazil
Luiz Gustavo de Quadros, Department of Endoscopy, Beneficência Portuguesa Hospital, ABC Medical School, São Bernardo 15015 110, Brazil
Richard K Burt, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, United States
Author contributions: Ruiz MA, Kaiser Junior RL and Burt RK conceived the study, drafted and reviewed the manuscript; Piron-Ruiz L, Saran PS, and De Quadros LG contributed to the literature review, discussed the subject and reviewed the final manuscript text; Castiglioni L and Pinho TS provided statistical support; All authors approved the final version of the article.
Conflict-of-interest statement: Authors declare no conflict of interests for this article.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Corresponding author: Milton Artur Ruiz, MD, PhD, Emeritus Professor, Department of Bone Marrow Transplant, Beneficência Portuguesa Hospital, Rua Catarina Nucci Parise 760, São José do Rio Preto 15090 470, Brazil. milruiz@yahoo.com.br
Received: May 2, 2020
Peer-review started: May 2, 2020
First decision: May 24, 2020
Revised: July 8, 2020
Accepted: August 25, 2020
Article in press: August 25, 2020
Published online: October 26, 2020
Abstract

Crohn's disease (CD) is a chronic inflammatory bowel disease that can affect any part of the gastrointestinal tract. The etiology of CD is unknown; however, genetic, epigenetic, environmental, and lifestyle factors could play an essential role in the onset and establishment of the disease. CD results from immune dysregulation due to loss of the healthy symbiotic relationship between host and intestinal flora and or its antigens. It affects both sexes equally with a male to female ratio of 1.0, and its onset can occur at any age, but the diagnosis is most commonly observed in the range of 20 to 40 years of age. CD diminishes quality of life, interferes with social activities, traumatizes due to the stigma of incontinence, fistulae, strictures, and colostomies, and in severe cases, affects survival when compared to the general population. Symptoms fluctuate between periods of remission and activity in which complications such as fistulas, strictures, and the need for bowel resection, surgery, and colostomy implantation make up the most severe aspects of the disease. CD can be progressive and the complications recurrent despite treatment with anti-inflammatory drugs, corticosteroids, immunosuppressants, and biological agents. However, over time many patients become refractory without treatment alternatives, and in this scenario, hematopoietic stem cell transplantation (HSCT) has emerged as a potential treatment option. The rationale for the use of HSCT for CD is anchored in animal studies and human clinical trials where HSCT could reset a patient's immune system by eliminating disease-causing effector cells and upon immune recovery increase regulatory and suppressive immune cells. Autologous HSCT using a non-myeloablative regimen of cyclophosphamide and anti-thymocyte globulin without CD34+ selection has been to date the most common transplant conditioning regimen adopted. In this review we will address the current situation regarding CD treatment with HSCT and emphasize the medical, ethical, and legal aspects that permeate the procedure in Brazil.

Keywords: Crohn disease, Hematopoietic stem cell transplant, Stem cell therapy, Autologous transplant, Ethics, Treatment

Core Tip: Hematopoietic stem cell transplantation (HSCT) is an alternative treatment for patients with Crohn's disease, which is severe and refractory to conventional treatments. Prolonged remissions are described with the autologous as in the allogeneic modality. In this review, we describe the rationale, justifications, and results of HSCT in studies from various locations. Unpublished data and results from a relevant series are described. The ethical and legal medical aspects that permeate compassionate treatment in Brazil are defined and presented.