High-Dose Immunosuppressive Therapy (Cyclophosphamide and Campath-1H) Followed by Autologous Hematopoietic Stem Cell Transplantation In the Treatment of Systemic Sclerosis.

Abstract 4594

Systemic sclerosis (SSc) is an autoimmune disease characterized by vasculopathy and fibrosis. Patients with diffuse cutaneous subset and organ involvement have poor prognosis and require more effective therapeutic strategies. Recent data show that high-dose immunosuppressive therapy and autologous hematopoietic stem cell transplantation (autoHSCT) may result in clinical improvement in two thirds of those patients when applied in the early course of disease. Between 2003 and 2010 six patients suffering from severe SSc were treated with autoHSCT in Hematology and BMT Department of Medical University of Silesia (SUM) in Katowice, Poland in cooperation with Department of Internal Medicine and Rheumatology of SUM in Katowice. Patients with diffuse SSc (modified Rodnan skin score (mRSS) 16 or greater) and organ (respiratory or cardiac) involvement were enrolled. Patients with progressive pulmonary disease defined as at least 15% decrease in forced vital capacity (FVC) or diffusion capacity of the lung for carbon monoxide (DLCO) in the previous 6 months were also included. Study group characteristic before autoHSCT: 6 patients with diffuse subset of SSc (4 women, 2 men), median age 54 years (30-68), disease duration 24 months (10-87), mRSS 19 (17-34), DLCO 51% (32-77), forced vital capacity (FVC) 70% (62-101), left ventricle ejection fraction 61% (60-70), serum creatinine level 0.8 mg/dL (0.5-1.1), organ dysfunction: lung (4/6 pts); kidney (0/6); heart (3/6); gastrointestinal tract (3/6), autoantibodies: antinuclear (5/6), Scl-70 (5/6), prior therapy: corticosteroids (4/6), cyclophosphamide (5/6). Peripheral blood stem cells were mobilized with G-CSF (10μ g/kg/d) subcutaneously with the first apheresis scheduled on day 5. The number of aphereses required for collection of stem cells was 3.5 (1-5). Cell selection before transplantation was not performed. Conditioning regimen included cyclophosphamide at total dose 200mg/kg given on days -6 to -3 and Campath-1H at total dose 60mg on days -3 to -1 as iv vivo purging of lymphocytes. The median number of transplanted CD34+ cells was 2.6 (2.1-8.1). One patient (68 years old woman with cardiac and lung involvement before transplantation) died three days after autoHSCT because of circulatory insufficiency. All remaining five patients engrafted. Hematopoietic recovery was as follows: neutrophil count above 500/μ l 12 days (9-16), platelet count above 20 000/μ l 8 (7-14). Main early complications after transplantation were infections (bacterial pneumonia – 1 pt, CMV reactivation – 1, FUO – 3, mucositis - 3) and cardiac arrhythmias. Five of six patients are alive at a median observation time 2.5 years (0.5-7). All of them achieved disease improvement after autoHSCT. Major improvement was seen in skin (mRSS) and disability index. Organ function remained stable. Autoantibodies are still detectable. In one case disease progression occured 1.5 years after transplantation requiring systemic treatment. Remaining 4 patients have sustained response without post-transplant therapy. Despite small number of cases this report shows that durable responses can be achieved in the majority of patients with diffuse SSc after autoHSCT. Early qualification to the procedure before severe organ dysfunction occurs is essential to achieve sustained remissions and reduce transplant related mortality. Our findings are consistent with outcomes reported in the literature. Results from prospective randomized clinical trials, such as ASTIS and SCOT trials, comparing high-dose immunoablation and autoHSCT with standard cyclophosphamide therapy will finally determine efficacy of this new treatment modality.