Z Gastroenterol 2011; 49 - V129
DOI: 10.1055/s-0031-1285265

High-dose cyclophosphamide and autologous hematopoieitic cell transplantation for inflammatory bowel disease – a single center experience

P Hasselblatt 1, K Drognitz 2, K Potthoff 2, H Bertz 2, W Kruis 3, C Schmidt 4, A Stallmach 4, J Finke 2, W Kreisel 1
  • 1Freiburg University, Dept. of Medicine II, Freiburg, Germany
  • 2Freiburg University, Dept. of Medicine I, Freiburg, Germany
  • 3Ev. Krankenhaus Köln, Cologne, Germany
  • 4University Hospital Jena, Dept. of Gastroenterology, Jena, Germany

Background: Despite recent advances in immunosuppressive therapy, up to 10% of patients with severe inflammatory bowel disease remain refractory to conventional treatment. Recent studies show that immune ablation by high-dose immunsuppression and autologous peripheral blood hematopoietic cell transplantation (aPBHCT) may efficiently induce long-lasting clinical remission in autoimmune disease.

Methods: We conducted a phase I/II single center trial of a two step approach of aPBHCT in 8 patients with Crohn's disease (CD) and 2 patients with ulcerative colitis (UC) refractory to conventional treatment. Step 1 included collection of CD34+ selected hematopoietic stem cells after mobilization with cyclophosphamide (CTX, 2×2g/m2) and granulocyte-colony stimulating factor (G-CSF). Step 2 contained a conditioning regimen with high-dose CTX (50mg/kg BW day -5 to -2) followed by aPBHCT. Initially, patients already in remission after step 1 were observed without aPBHCT.

Results: Both UC patients showed only transient remission after step 1 and relapsed early, requiring proctocolectomy 2 and 4 months after mobilization, respectively. In contrast, step 1 resulted in good clinical and endoscopic improvement up to 20 months in all CD patients (n=8). Of those, two relapsed severely after 6 months, underwent surgery and were well managed with conventional immunosuppression thereafter. Step 2 including aPBHCT was performed in 6 of 8 patients with CD. All 6 transplanted patients achieved clinical remission while mucosal healing was observed in 4 patients. During follow up (median 1.8yrs) relapses occurred in 3 patients after 8, 10 and 12 months, respectively, but disease activity could easily be controlled by corticosteroids and conventional immunosuppressive therapy. Overall therapy was well tolerated without unexpected or serious side effects.

Conclusion: Immune ablation by CTX followed by aPBHCT is feasible, safe and effective in treating patients with refractory CD while it showed no benefit in UC. We propose that aPBHCT should be performed early because mobilization therapy alone is not adequate to prevent early relapses. Furthermore maintenance with low dose immunosuppressive therapy should be initiated early following aPBHCT to stabilize clinical remission.