2nd Annual BMRP Investigator Meeting - Abstract

Immune Ablation and Hematopoietic Stem Cell Support in Patients with Severe Crohn’s Disease

Robert Craig^a, Yu Oyama, Ann Traynor, Mary Brush, Kathleen Quigley, Amy Halverson and Richard Burt

Department of Medicine, Northwestern University Medical School (Chicago, Illinois, U.S.A.)

Aim: Bone marrow ablation and hematopoietic stem cell support (HSCT) is being studied in an effort to ascertain its value in inducing a clinical remission in severe Crohn’s disease (CD).

Methods: Patients with severe CD who have failed standard therapy (5-ASA, antibiotics, corticosteroids, immunosuppression, and infliximab), whose CDAI was > 250, were accessed for therapy.  Stem cells were mobilized from the peripheral blood using cyclophosphamide (2.0 g/m2) and G-CSF (10 mg/kg/day), enriched ex vivo by CD34+ selection (Isolex), and reinfused after immune conditioning with cyclophosphamide (200 mg/kg) and anti-thymocyte globulin (90 mg/kg).  HSCT was complicated by 24-48 hours of culture negative fever.

Results: Patients’ diarrhea and abdominal pain resolved prior to hospital discharge.  Perianal fistulae gradually closed over several months, and abdominal masses and colonic strictures have resolved.  One patient had progression of her small intestinal strictures following the transplantation requiring surgical resection (similar to observations in some patients receiving infliximab), but her post-operative course has been uneventful, and she continues to improve off all Crohn’s disease medications, and is currently in laboratory and clinical remission.  Two patients (8 months; 24 months) have persistent severe perianal disease, requiring anal superficial drainage with setons.  All patients have remained in remission in terms of the CDAI (<< 100) since HSCT (range 5-24 months) off all immune suppressive drugs and CD therapy.  Serum albumins, hemoglobins, weights, sedimentation rates, and CRPs, have improved or normalized.  In the two patients with the longest post HSCT course, small bowel radiographs have normalized in one and improved in the other.  Colonoscopy has revealed marked improvement, but superficial, asymptomatic ulcerations remain.

Conclusion: This preliminary experience in the first 12 patients who have received this unique therapy continues to be encouraging.  The depth and length of the clinical remission induced are still uncertain.

^aPrincipal Investigator