This study evaluates the safety and clinical benefits of a therapeutic approach using the cyclophosphamide (Cy) + thymoglobulin® (ATG) + granulocyte colony-stimulating factor (G-CSF) conditioning regimen followed by autologous hematopoietic stem cell transplantation (HSCT) rescue in the treatment of refractory Crohn's disease. Adverse events, and clinical and endoscopic conditions will be assessed at different short and long-term time points.
Crohn's disease (CD) is a chronic, refractory inflammatory bowel disease that affects the entire digestive tract associated with intestinal and extra intestinal manifestations or other autoimmune diseases. Conventional therapy for Crohn's disease includes anti-inflammatory, immunosuppressant and/or biologic drugs/corticosteroids. This treatment benefits the majority of patients. However, a proportion of patients fail to achieve complete and long-term disease control and often require multiple intestinal surgeries with a risk of developing short bowel syndrome. Hematopoietic stem cell transplantation (HSCT) has been proposed to cause lymphoablation and reset of the immune system as an alternative strategy to induce long-term disease control in this high-risk population. This study enrolled Crohn's disease patients not responsive to conventional therapy. Initially safety and the clinical outcome will be evaluated. The selected patients will be admitted to the bone marrow transplant (BMT) unit for the mobilization regimen using cyclophosphamide (Cy - 60 mg/kg) and G-CSF (10 mcg/kg/day) from the 5th day after Cy administration until harvesting progenitor cells from peripheral blood by leukapheresis. After seven days of rest, the conditioning regimen consists of Cy (200 mg/kg total dose for four days), rabbit antithymocyte globulin (6.5 mg/kg total dose for four days) and methylprednisolone (500 mg/day). The clinical course of patients with refractory Crohn´s disease will be evaluated to determine the efficacy of HSCT as a therapeutic tool including the adverse aspects of the procedure, clinical outcome and quality of life.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
50
Hematopoietic stem cell transplantation Lymphoablation followed by hematopoietic stem cell transplantation to rescue the immune system.
Beneficencia Portuguesa
São José do Rio Preto, São Paulo, Brazil
Safety of unselected autologous HSCT in refractory Crohn´s disease patients
HHSCT safety will be analyzed by laboratory tests and treatment-related adverse events. Safety will be evaluated by treatment-related adverse events. All adverse events will be recorded in a standardized way and their relationship to the study protocol will be assessed at different short- and long-term time points.
Time frame: 12 months
Crohn´s Disease Activity Index (CDAI)
Duration of disease remission, defined as a CDAI ≤ 150, will be assessed at 1, 3, 6, 12 and 24 months after transplant.
Time frame: 12 months
CRAIG Crohn´s Severity Score (CSS)
The CRAIG CSS will be assessed at 1, 3, 6, 12 and 24 months after transplant.
Time frame: 12 months
Inflammatory Bowel Disease Questionnaire (IBDQ)
The IBDQ will be administered at 1, 3, 6, 12 and 24 months after transplant.
Time frame: 24 months
Short Form-36 Health Survey (SF-36)
The SF-36 will be administered at 1, 3, 6, 12 and 24 months after transplant.
Time frame: 24 months
Simple Endoscopic Activity Score (SES)
The SES will be assessed at 6, 12 and 24 months after HSCT.
Time frame: 24 months
Crohn's Disease Endoscopic Index of Severity (CDEIS)
The CDEIS will be assessed at 6, 12 and 24 months after HSCT.
Time frame: 24 months
Rutgeerts endoscopic score
Rutgeerts endoscopic score will be assessed at 6, 12 and 24 months after HSCT.
Time frame: 24 months
Harvey & Bradshaw Index (HBI)
The HBI will be assessed at 1, 3, 6, 12 and 24 months after HSCT.
Time frame: 24 months
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