Autologous Hematopoietic Stem Cell Transplantation for Refractory Crohn’s Disease, the Summary of Phase I Trial.

Background &Aims

Crohn’s disease (CD) is an immunologically mediated inflammatory disease of the gastrointestinal tract. In theory, immune ablation followed by autologous hematopoietic stem cell transplantation (HSCT) can induce remission by reconstituting a new immune system.

Methods

We conducted a phase I HSCT study in 17 patients with severe CD. Candidates were less than 60 years old with a Crohn’s Disease Activity Index (CDAI) of 250–400 or Craig Crohn’s Severity Index (CCSI) of >17 despite conventional therapy including infliximab. Peripheral blood stem cells were mobilized with cyclophosphamide and granulocyte colony-stimulating factor and CD34+ enriched. The immune ablative conditioning regimen consisted of 200mg/kg cyclophosphamide, and 90mg/kg equine antithymocyte globulin.

Results

There was no treatment related mortality. The procedure was well tolerated with anticipated cytopenias, neutropenic fever, and disease-related fever, diarrhea, anorexia, nausea, vomiting. The median days for neutrophil and platelet engraftment were 9 (range 7–11) and 9 (range 8–18, three patients never below 20,000), respectively. The median infused CD34+ and CD3+ cell counts were 4.83 x 106/kg (range 1.73–24.88) and 0.56 x 104/kg (range 0.0–3.09), respectively. Initial median CDAI and CCSI were 282 (range 101–358) and 24 (range 18–33). Symptoms and CDAI/CCSI improved quickly and dramatically (figure), and radiographic and colonoscopy findings improved gradually over months to years following HSCT. For patients with >6 months follow up, twelve out of fifteen patients entered sustained remission defined by a CDAI < 150 or reduction of a CCSI >10 after median follow-up of 29 months (range 11–48).

Conclusion

Autologous HSCT can be performed safely and has a marked durable salutary effect on CD activity. A randomized study {KISS study: C(K)rohn’s Immune Suppression vs. Stem Cell Transplant} comparing HSCT to standard therapy is now enrolling patients.

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