Nonmyeloablative Hematopoietic Stem Cell Transplantation for the Treatment of Systemic Sclerosis.

Abstract

Systemic sclerosis (SSc) is an autoimmune disease which is characteristic of diffuse scleroderma and visceral organ fibrosis. Various kinds of therapies including immunosuppressive drugs have been attempted yet all proved ineffective. In order to reconstitute the immune system and cure SSc patients, we started a clinical trial of nonmyeloablative hematopoietic stem cell transplantation (NST) for the treatment of SSc. The inclusion criteria consisted of an age younger than 70 years, SSc as defined by Ministry of Health, Labor, and Welfare, a duration of less than 4 years since the diagnosis of SSc, a skin score of more than 15 points, and moderate organ failure. We herein describe the first patient to take part in this trial. A 52-year-old female suffered from scleroderma and we diagnosed to have SSc in 2000. Although she was treated with prednisolone, cyclophosphamide, penicilamine, and prostagrandin, the scleroderma was progressive (skin score 30 points) and the interstitial pneumonia also worsened (%VC 66.5 %, serum KL-6 level 1080 U/mL). In November 2003, we enrolled her as the first patient to undergo NST after her informed consent was obtained. After conditioning therapy consisting of low dose TBI (200 cGy) and fludarabine (30mg/m2, 3days), G-CSF-mobilized peripheral blood stem cells from an HLA- identical brother were infused.Graft-versus-host disease (GVHD) prophylaxis consisted of cyclosporine and mycophenolate mofetil. No blood transfusion was performed. Complete donor chimerism was obtained and has continued since 1 month after NST. The cyclosporine dosage was tapered gradually, and no apparent acute or chronic GVHD was seen. Three months after NST, the patient's skin score improved to 19 points and a skin biopsy showed mild lymphocyte infiltration. At 8 months after NST, the area of interstitial pneumonia decreased according to the computed tomography findings and the %VC levels and serum KL-6 level were both found to have substantially improved (70.3 % and 746 U/mL, respectively). Although the duration after NST is still short, the clinical course for this patient is presently appears to be promising.