Autologous hematopoietic stem cells for refractory Crohn’s disease

ABSTRACT

Introduction: Autologous hematopoietic stem cells are gaining ground as an effective and safe treatment for treating severe refractory Crohn’s disease (CD). Autologous hematopoietic stem cell therapy (AHSCT) induces resetting of the immune system by de novo regeneration of T-cell repertoire and repopulation of epithelial cells by bone-marrow derived cells to help patients achieve clinical and endoscopic remission.

Areas covered: Herein, the authors discuss the use of AHSCT in treating patients with CD. Improvements in disease activity have been seen in patients with severe autoimmune disease and patients with severe CD who underwent AHSCT for a concomitant malignant hematological disease. Clinical and endoscopic remission has been achieved in patients treated with AHSCT for CD. The only randomized trial published to date, the ASTIC Trial, did not support further use of AHSCT to treat CD. Yet, critics of this trial have deemed AHSCT as a promising treatment for severe refractory CD.

Expert opinion: Even with the promising evidence presented for HSCT for refractory CD, protocols need to be refined through the collaboration of GI and hemato-oncology professionals. The goal is to incorporate safe AHSCT and restore tolerance by delivering an effective immune ‘cease fire’ as a treatment option for severe refractory CD.

KEYWORDS:

• Crohn’s disease (CD)
• autologous hematopoietic stem cell transplant (AHSCT)
• hematopoietic stem cells (HSC)
• autoimmune diseases
• immune system

Article highlights

• The rationale for AHSCT is the resetting of the immune system by immediate immune ‘cease fire’ by de novo regeneration of the T-cell compartment and BM-derived cells to restore damaged epithelial cells.

• AHSCT consists of mobilization, leukapheresis, and conditioning. Stem cells are mobilized from the bone marrow to the peripheral blood stream. Then PBSC are collected, separated and stored. Finally, the patient undergoes conditioning chemotherapy followed by reinfusion of stem cells to begin renewal of the immune system.

• Multiple studies have evaluated AHSCT as a treatment specifically for severe refractory CD. Patients have achieved clinical and endoscopic remission, but have also experienced some adverse events and complications requiring strict safety measures to be taken during therapy.

• The only randomized controlled trial, ASTIC trial, had few patients who achieved clinical and endoscopic remission leading the authors to recommend against AHSCT for CD. However, critics have deemed the primary endpoints too strict highlighting the need for further study of AHSCT. Additionally, the amount of CP in mobilization phase was considerably higher than that used in the Burt et al. (2010) study and the ASTIC trial did not have a valid control group.

• In order to compare the ASTIC trial and the Burt et al. (2010) study, additional data is needed from the ASTIC trial, including clinical remission rate 5 years post transplantation, CSI scores, and percent in steroid and immunosuppressant-free remission.

• Refined protocols and increased safety measures to minimize toxicity of AHSCT are recommended for future research.

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Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Additional information

Funding

This manuscript has not been funded.