Autologous Hematopoietic Stem Cell Transplantation in Refractory Crohn's Disease. Experience of Tertiary Medical Center in Brazil

Abstract

Background Crohn's disease (CD) is a chronic inflammatory and relapsing disease that can affect any segment of the gastrointestinal tract. A significant percentage of these patients suffer an aggressive disease course, refractory to conventional clinical therapy . Surgery may be required, however the disease tends to recur after the resection. Aim Describe the potential clinical benefit of autologous hematopoietic stem cell with T-lymphocyte-depletion as a treatment for aggressive and refractory CD patients. Evaluate its efficacy, safety, toxicity and adverse events and primary and secondary clinical outcomes of follow up after 1year and 3 years. Methods We evaluated 6 patients submitted to an autologous HSCT. All patients were mobilized with cyclophosphamide (Cy) and G-CSF at the dose of 10mcg/kg/dia, The collection of HSC was initiated when the CD34+ count in the peripheral blood was greater than 15cels/mm3. The harvested product was enriched with CD34 + cells through a CliniMacs (Miltenyi Biotec) with a target CD34 + cells above 2.0 × 10E6/kg and less than 1 × 10E4Tcells/kg. The conditioning regimen consisted of cyclophosphamide 50mg/kg for 4 consecutive days, thymoglobulin 1.5mg/kg and methylprednisolone 1g/day from d-5 to d-2. Results Five patients refractory CD, between 43y and 19y (median age 38y), were included and follow the autologous HSCT. Corporal index mass 20 Kg/m2, median course of illness 14y, all negative for X-linked inhibitor apoptosis protein (XIAP). Four patients had penetrating disease and two patients had nonstricturing nonpenetrating phenotipe. Five patients had 2 to 3 previous intestinal surgeries. All patients used aminosalicylates steroids, thiopurines, metotrexate and more than one immunobiological therapies (IFX, ADA, VDZ). All six patients completed the mobilization, conditioning and transplantation phases, during a median time of hospitalization of 35 days. The median of CD34+ cels infused was 7.7 × 10e6/kg. All patients achieved engraftment, with a sustained median neutrophil count of 0.5 × 109/L at a median of 11 days and platelet grafting was 10 days. All patients had life-threatening complications as infectious (KPC, Staphylococcus aureus and septic by E. coli), febrile neutropenia and non-infectious complications as anemia mucositis and red cell transfusion was required. After 1y HSCT, all patients achieved the 1ary and 2nd outcomes: clinical and endoscopic remission (fig) and were steroid and immunosuppressive free remission (CDAI Conclusion HSCT is a complex treatment strategy for severe CD associated with mortality and serious adverse events. Due to its high complexity, risk of infections and death the balance between risks and benefits becomes significantly important in this therapy.