Medical, ethical, and legal aspects of hematopoietic stem cell transplantation for Crohn’s disease in Brazil

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.

Stem Cell-Based Therapies for Inflammatory Bowel Disease

“…Notably, at this stage in clinical studies, autologous HSCT using a non-myeloablative regimen of cyclophosphamide and anti-thymocyte globulin without sorting CD34 + cell is the most common transplant pretreatment regimen. Although a limited number of phase I-III HSCT trials have shown promising results, and some patients can benefit in some dimensions, but relapse makes it challenging to classify HSCT as an effective treatment, and larger samples and longer-term efficacy observations are needed [ 94 ].…”

Effects of Posaconazole on Tacrolimus Population Pharmacokinetics and Initial Dose in Children With Crohn’s Disease Undergoing Hematopoietic Stem Cell Transplantation

“…Uncontrolled inflammation results in long-term complications, including enteric fistulae, fibrotic strictures, and intestinal neoplasia ( Cushing and Higgins, 2021 ). These symptoms may be observed in childhood as an outcome of undergoing surgical operation and may ultimately develop into short gut syndrome ( Ruiz et al, 2020 ). The treatment outcomes for CD are not entirely satisfactory ( Ruiz et al, 2020 ).…”

“…These symptoms may be observed in childhood as an outcome of undergoing surgical operation and may ultimately develop into short gut syndrome ( Ruiz et al, 2020 ). The treatment outcomes for CD are not entirely satisfactory ( Ruiz et al, 2020 ). For example, prescription medication treatments require prolonged treatment, and some patients become refractory.…”

“…For example, prescription medication treatments require prolonged treatment, and some patients become refractory. In addition, recurrent surgeries force patients to search for alternative treatments, including hematopoietic stem cell transplantation (HSCT) ( Ruiz et al, 2020 ).…”

“…It has been reported that HSCT significantly improves the quality of life of CD patients, and 50% of CD patients who underwent HSCT achieved complete healing of the mucosa and clinical remission ( Lindsay et al, 2017 ; Lopez-Garcia et al, 2017 ; Ruiz et al, 2020 ). However, for HSCT patients, long-term tacrolimus treatment is necessary to prevent rejection ( Gao and Ma, 2019 ; Ishiwata et al, 2020 ; Soskind et al, 2020 ; Zhou et al, 2020 ).…”