Remission of refractory Crohn's disease after autologous hematopoietic stem cell transplantation

Ruiz, Milton Artur; Kaiser, Roberto Luiz; Faria, Mikaell Alexandre Gouvêa; Quadros, Luiz Gustavo de

doi:10.1016/j.bjhh.2015.01.002

Cited by 8 publications

(5 citation statements)

References 17 publications

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“…Communications took place in meetings, congresses, scientific events, and case reports of patients from the study projects[ 37 - 40 ]. The Brazilian Medical Society, with involvement and authority over HSCT, including CD, is the Brazilian Society of Bone Marrow Transplantation (SBTMO).…”

Section: And Hsct In Brazilmentioning

confidence: 99%

“…Finally, of note, Brazil's first report of HSCT in CD occurred in 2013 at Beneficencia Portuguesa Hospital of São José do Rio Preto, São Paulo[ 37 ] in a female patient with severe CD, refractory to anti-inflammatory agents, corticosteroids, immunosup-pressants, and two biological anti-TNF α drugs, infliximab, and adalimumab. She had repeated episodes of abdominal pain, more than 20 bowel movements/day, hematochezia, weight loss, depression, psychosis, arthralgia, psoriatic-like skin lesions, and a prior 40 cm bowel resection due to stenosis.…”

Section: And Hsct In Brazilmentioning

confidence: 99%

“…Before HSCT, colonoscopy showed severe ileitis in the ileum cecal valve, right and left colon, and rectum. The patient has remained in a drug-free clinical and endoscopic remission, more than five years after HSCT[ 37 ].…”

Section: And Hsct In Brazilmentioning

confidence: 99%

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

Ruiz¹,

Kaiser²,

Piron-Ruiz³

et al. 2020

WJSC

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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.

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Section: And Hsct In Brazilmentioning

confidence: 99%

Section: And Hsct In Brazilmentioning

confidence: 99%

See 1 more Smart Citation

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

Ruiz¹,

Kaiser²,

Piron-Ruiz³

et al. 2020

WJSC

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“…Therefore, if considering the invasiveness and the risks of morbidity and mortality related to HSC transplantation that hamper its use in nonlife‐threatening conditions, it appears clear that MSC are the best candidate as the lack of expression of histocompatibility locus antigen (HLA) class II and costimulatory molecules and the low levels of HLA class I antigens enables their transplantation across HLA barriers without a preventive immunoablative regimen . Specifically, a number of adverse events, including both neutropenic‐ and infection‐related fever, hemorrhagic complications, mucositis, and acute renal failure, have been reported when using HSC transplantation in the autologous setting . Remarkably, also a case of conditioning‐related mortality, with postmortem evidence of sinusoidal obstructive syndrome has been described.…”

Section: Cellular Therapies In Inflammatory Bowel Diseasementioning

confidence: 99%

“…To date, a total of 138 cases have been described (Table ) who were rescued from an invalidating condition by this therapeutic strategy despite the withdrawal of drugs in most of them . However, the lack of objective data on mucosal healing in several cases may have resulted in an overestimation of the success rate.…”

Section: Cellular Therapies In Inflammatory Bowel Diseasementioning

confidence: 99%

Concise Review: Cellular Therapies: The Potential to Regenerate and Restore Tolerance in Immune-Mediated Intestinal Diseases

2016

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Chronic inflammatory enteropathies, including celiac disease, Crohn's disease, and ulcerative colitis, are lifelong disabling conditions whose cure is still an unmet need, despite the great strides made in understanding their complex pathogenesis. The advent of cellular therapies, mainly based on the use of stem cells, represents a great step forward thanks to their multitarget strategy. Both hematopoietic stem cells (HSC) and mesenchymal stem/stromal cells (MSC) have been employed in the treatment of refractory cases with promising results. The lack of immunogenicity makes MSC more suitable for therapeutic purposes as their infusion may be performed across histocompatibility locus antigen barriers without risk of rejection. The best outcome has been obtained when treating fistulizing Crohn's disease with local injections of MSC. In addition, both HSC and MSC proved successful in promoting regeneration of intestinal mucosa, and favoring the expansion of a T-cell regulatory subset. By virtue of the ability to favor mucosal homeostasis, this last cell population has been exploited in clinical trials, with inconsistent results. Finally, the recent identification of the epithelial stem cell marker has opened up the possibility of tissue engineering, with an array of potential applications for intestinal diseases. However, the underlying mechanisms of action of these interconnected therapeutic strategies are still poorly understood. It is conceivable that over the next few years their role will become clearer as the biological interactions with injured tissues and the hierarchy by which they deliver their action are unraveled through a continuous moving from bench to bedside and vice versa. STEM CELLS 2016;34:1474-1486 SIGNIFICANCE STATEMENTThe advent of cellular therapies, mainly based on the use of stem cells, represents a great step forward in the treatment and, possibly, the cure of chronic inflammatory conditions, including immune-mediated enteropathies. By virtue of the ability to favor tissue regeneration and expansion of T cells with regulatory function, mesenchymal stem cells seem the best candidate. Moreover, the lack of immunogenicity makes them perfectly suitable in these nonlifethreatening conditions as their infusion may be performed across histocompatibility locus antigen barriers without the immunoablative regimen. However, further investigations are needed to discover the underlying mechanisms of action of these novel therapeutic strategies.

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Stem cell transplantation for induction of remission in medically refractory Crohn’s disease

El‐Nakeep

Latif

Shawky

et al. 2018

Cochrane Database of Systematic Reviews

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Remission of refractory Crohn's disease after autologous hematopoietic stem cell transplantation

Cited by 8 publications

References 17 publications

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

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

Concise Review: Cellular Therapies: The Potential to Regenerate and Restore Tolerance in Immune-Mediated Intestinal Diseases

Stem cell transplantation for induction of remission in medically refractory Crohn’s disease

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