These authors contributed equally.
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Original Article
Remission of refractory Crohn's disease by high-dose cyclophosphamide and autologous peripheral blood stem cell transplantation
Article first published online: 2 SEP 2012
DOI: 10.1111/apt.12032
© 2012 Blackwell Publishing Ltd
Additional Information
How to Cite
Aliment Pharmacol Ther 2012; 36: 725–735
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These authors contributed equally.
Publication History
- Issue published online: 17 SEP 2012
- Article first published online: 2 SEP 2012
- Manuscript Accepted: 10 AUG 2012
- Manuscript Revised: 31 JUL 2012
- Manuscript Revised: 24 JUN 2012
- Manuscript Received: 12 JUN 2012
Funded by
- University Hospital Freiburg
Summary
Background
Despite advances in immunosuppressive therapy, up to 10% of patients with severe Crohn's disease (CD) remain refractory to conventional treatment. Limited evidence from pilot trials suggests that high-dose immunosuppression and autologous peripheral blood stem cell transplantation (autoPBSCT) may induce remission in these patients, but there is substantial controversy regarding the safety and efficacy of this approach.
Aim
To address this issue, a monocentre phase I/II trial of autoPBSCT was performed in patients with refractory CD in our hospital.
Methods
Here, we report on the outcome of 12 patients with refractory CD treated with autoPBSCT. Briefly, CD34+-selected PBSCs were harvested after mobilisation therapy with cyclophosphamide and granulocyte-colony stimulating factor. Later, immunoablative conditioning therapy with high-dose cyclophosphamide followed by autoPBSCT was applied and clinical and endoscopic responses were analysed after a mean follow-up of 3.1 years (range 0.5–10.3 years).
Results
PBSC harvest following mobilisation chemotherapy was successful in 11/12 patients and resulted in a clinical and endoscopic improvement in 7/12 patients. Subsequent conditioning and autoPBSCT were performed in nine patients and were relatively well tolerated. Among those, five patients achieved a clinical and endoscopic remission within 6 months after autoPBSCT. However, relapses occurred in 7/9 patients during follow-up, but disease activity could be controlled by low-dose corticosteroids and conventional immunosuppressive therapy.
Conclusion
Immunoablation by cyclophosphamide and autologous peripheral blood stem cell transplantation is safe and effective to induce remission of refractory Crohn's disease, and should be further evaluated in randomised controlled trials.