Autologous Hematopoietic Stem Cell Transplantation for Systemic Sclerosis

Francesca      Milanetti; Jurate      Bucha; Alessandro      Testori; Richard      K. Burt

Abstract

Systemic sclerosis is a rare disorder manifesting as skin and internal organ fibrosis, a diffuse vasculopathy, inflammation, and features of autoimmunity. Patients with diffuse cutaneous disease or internal organ involvement have a poor prognosis with high mortality. To date no therapy has been shown to reverse the natural course of the disease. Immune suppressive drugs are commonly utilized to treat patients, but randomized trials have generally failed to demonstrate any long-term benefit. In phase I/II trials, autologous hematopoietic stem cell transplantation (HSCT) has demonstrated impressive reversal of skin fibrosis, improved functionality and quality of life, and stabilization of internal organ function, but initial studies were complicated by significant treatment-related mortality. Treatment-related mortality was reduced by better pre-transplant evaluation to exclude patients with compromised cardiac function and by treating patients earlier in disease, allowing selected patients the option of autologous HSCT treatment. There are currently three ongoing randomized trials of autologous HSCT for systemic sclerosis: ASSIST (American Systemic Sclerosis Immune Suppression versus Transplant), SCOT (scleroderma cyclophosphamide versus Transplant), and ASTIS (Autologous Stem cell Transplantation International Scleroderma). The results from these trials should clarify the role of autologous HSCT in the currently limited therapeutic arsenal of severe systemic sclerosis.

Keywords: Scleroderma, systemic sclerosis, hematopoietic stem cell, transplantation, organ fibrosis, diffuse vasculopathy,, autoimmunity, diffuse cutaneous disease, ASSIST, SCOT, ASTIS, acro-sclerosis, Raynaud's phe-nomena, metacarpal-phalangeal joints, sclerodactyly, rheumatoid arthritis, systemic lupus erythematosus, polymyositis, Sjogren's syndrome, mixed connective tissue disease, anti-centromere antibodies, anti-topoisomerase antibodies, morphea, pulmonary fibrosis, biliary cirrhosis, retroperitoneal, myocardial fibrosis, gastrointestinal fibrosis, peristalsis, te-langiectasia, gastric an-tral vascular ectasis or GAVE, pleuritis, pericarditis, my-ositis, synovitis, alveolitis, Nailfold capillary microscopy (NBM), endothelial progenitor cells, angiogenesis, Medsger score, vascular endothelial growth, Anti-nuclear antibodies (ANA), anti-RNA polymerase III (anti-RNAPIII), antifibrillin-1 (anti-FBN1), extracellular matrix (ECM), Anticardiolipin antibodies (ACLA), thrombosis, antiphospholipid antibodies, lupus antico-agulant, univariate analysis, anaemia, erythrocyte sedimentation rate (ESR), proteinuria, tumor necrosis factor (sTNF), arrhythmia, nifedipine, amlodipine, bosentan (endothelin 1 inhibitor), sildenafil, prednisone, methotrexate, azathioprine, cyclophosphamide, mycophenolate mofetil, cyclosporine, chloroquine, D-penicillamine, interstitial lung disease (ILD), placebo, corticosteroids, T-lymphocytes, B-lymphocytes, macrophages, dendritic cells, leukapheresis, lymphopenia, neutropenia, telangiectasias, arthralgias, peripheral blood stem cells, cy-tomegalovirus, myeloablative, leukemia, myelodysplastic syndrome, total body irradiation, pul-monary hypoxia, pulmonary vascular resistance, pulmonary capillary wedge, cardiac output, high resolution computed tomography, total lung capacity (TLC), forced vital capacity (FVC), gastric antral vascular ectasia), ma-lignancies