P471. Hematopoietic stem cell transplantation in refractory Crohn's disease: Feasibility and toxicity
A. Jauregui-Amezaga1, M. Rovira2, S. Pinó Donnay1, P.J. Marín2, F. Feu1, J.I. Elizalde1, F. Fernández-Avilés2, C. Martínez2, L. Rosiñol2, M. Suarez-Lledó2, M.C. Masamunt1, A. Ramírez-Morros1, M. Gallego1, I. Ordás1, J. Panés1, E. Ricart1, 1Hospital Clínic de Barcelona, Gastroenterology Department, Barcelona, Spain, 2Hospital Clínic de Barcelona, Hematology Department, Barcelona, Spain
Autologous hematopoietic stem cell transplantation (HSCT) is a second line treatment for severe refractory Crohn's disease (CD) patients. We evaluated feasibility and toxicity of autologous HSCT for refractory CD.
In this prospective study, refractory CD patients with an aggressive course despite medical treatment, impaired quality of life and no surgical options were included. Hematopoietic stem cells were mobilized (cyclophosphamide and granulocyte colony-stimulating factor) and collected by leukapheresis from peripheral blood. In a second step, a non-myeloablative conditioning regimen with cyclophosphamide and rabbit antithymocite globulin (rATG) was used and previously collected stem cells were infused. Toxicity and complications during mobilization and conditioning phases and first-year follow up were evaluated.
Twenty-six patients were included. Infectious complications during mobilization included 16 febrile neutropenias, 1 bacteriemia, and 2 bacteriemias associated with septic shock (2 of 3 isolated microorganisms were multi-drug resistant bacteria). Neutropenia median time was 5 days and hospitalization median time was 18 days. Five patients did not continue to the second phase of the study: leukapheresis was not successful in 2 patients, 1 patient withdrew the study after mobilization, another one required surgery and the fifth one reached clinical remission after mobilization, so 21 patients entered into the conditioning phase. Hospitalization median time was 26 days, hematopoiesis recovery median time for neutrophils (>1×109/L) was 12 days and for platelets (>20×109/L) 4 days. Red cell transfusion was required in all patients. For infectious complications, 95% of patients presented febrile neutropenia, 8 Gram-positive coccus were isolated, 2 Gram-negative bacilli were identified after neutrophil recovery and 3 patients presented worsening of perianal CD activity. Among non-infectious complications, 6 patients suffered rATG reaction, 12 mucositis and 2 hemorrhagic complications. Infectious complications during the study prompted us to revise and intensify supportive measures as well as to introduce new empirical antibiotic schedules. During the first 12-month follow up, viral infections were the most common and in one patient, cytomegalovirus led to multiorganic failure and death.
Autologous HSCT for refractory CD patients is feasible if extraordinary supportive measures are applied. We consider that this procedure should only be developed in high-experienced centers applying the same security measures than those used for allogeneic transplantation.