Autologous Haematopoietic Stem Cell Transplantation (AHSCT) in Severe Crohn’s Disease: A Review on Behalf of ECCO and EBMT

Abstract

Despite the major recent progress in the treatment of Crohn's disease [CD], there is a subset of patients in whom the disease runs an aggressive course with progressive tissue damage requiring early and repeated surgical management. Increasing evidence supports sustained and profound improvement in gastrointestinal parameters and quality of life following high-dose immunosuppressive therapy and autologous haematopoietic stem cell transplantation [AHSCT] compared to standard therapy in this context. In addition, international transplant registry data reflect the use of AHSCT in CD outside of trials in selected patients. However, AHSCT may be associated with significant treatment-related complications with risk of transplant-related mortality. In a joint initiative, the European Crohn's and Colitis Organisation [ECCO] and the European Society for Blood and Marrow Transplantation [EBMT] have produced a state-of-the-art review of the rationale, evaluation, patient selection, stem cell mobilization and transplant procedures and long-term follow up. Given the unique spectrum of issues, we recommend that AHSCT should only be performed in experienced centres with expertise in both haematological and gastroenterological aspects of the procedure. Where possible, patients should be enrolled on clinical trials and data registered centrally. Future development should be coordinated at both national and international levels.

Indications for haematopoietic stem cell transplantation for haematological diseases, solid tumours and immune disorders: current practice in Europe, 2019

“…Since then, recent studies have increased the evidence base for autologous HSCT in some indications, including multiple sclerosis [167][168][169][170][171], systemic sclerosis [172][173][174][175], Crohn's disease [176][177][178] and systemic lupus erythematosus [179]. Disease-specific recommendations are increasingly available from the EBMT and other professional societies as the evidence base for autologous HSCT growth [180][181][182][183]. Allogeneic HSCT has been predominantly used in the paediatric setting [164], particularly in patients with refractory autoimmune cytopenia and juvenile idiopathic arthritis [184,185].…”

“…Crohn's disease is a potential indication for autologous HSCT, but allogeneic HSCT is appropriate for monogenic forms of inflammatory bowel disease (e.g. interleukin-10 signalling defects, immunodysregulation polyendocrinopathy enteropathy X-linked syndrome, Wiskott-Aldrich syndrome or increasingly X-linked inhibitor of apoptosis deficiency] [182]. Allogeneic HSCT may result in longterm responses in severe juvenile inflammatory arthritis [185].…”

Autologous haematopoietic stem cell transplantation (aHSCT) for severe resistant autoimmune and inflammatory diseases – a guide for the generalist

“…Surgical resection may not be feasible or may be declined by the patient if it will result in a permanent stoma. 6 Initial case series and single-centre cohort studies suggested that aHSCT could induce sustained clinical benefit. To date there has only been one randomised controlled trial to assess the value of aHSCT in refractory CD, the ASTIC trial 18 (see Table 3 ).…”

“…Significantly, the majority of patients who relapsed after aHSCT subsequently responded to reintroduction of anti-TNF therapy. 6,20 Further research is required to assess the place of aHSCT in the management of patients with treatment refractory and poor prognosis CD. ASTIClite is an NIHR-funded randomised controlled trial that will assess the benefit and risks of a low intensity mobilisation and conditioning HSCT regimen compared to the best currently available medical care in patients with significant CD refractory to at least two classes of biologic therapy.…”

Application of tissue engineering in perianal Crohn´s Disease

“…Snowden et al publicó resultados similares a los descritos, en los que la carga de efectos adversos tras el TPHA era alta. Sin embargo, los pacientes respondían mejor a la terapia convencional que había sido suspendida previa al trasplante y a la que eran refractarios en un principio (28). Otros ensayos, como el de Lindsay et al recogen resultados de efectos adversos frecuentes y graves tras el trasplante como la muerte de un paciente por síndrome sinusoidal (29).…”