Systemic scleroderma (SSc) is an autoimmune disease, manifesting as skin and internal organ fibrosis and vasculopathy. Nowadays despite the advances in immunosuppression there are still many patients with treatment-refractory SSct, which may lead to multiple organ failure and a fatal income. Stem cell transplantation seems to be a promising modern therapeutic approach to this problem.
To assess the efficacy of autologous haematopoietic stem cell transplantation (HSCT) in patients with treatment-refractory SSc.
A total of 23 female patients with SSc with involvement of internal organ and skin, aged 42.91±7.82 (M±SD) underwent HSCT. Disease duration was 8.52±6.16 years. Before cell therapy all patients received standard treatment such as immunosuppression and glucocorticosteroids.
Patients were treated with HSCT according to the scheme – 0-3-6-12 months. The operation was conducted in two stages: 1) mielotransplantation with following biotechnological separation of hematopoietic stem cells fraction; 2) intravenous cells infusion at 50 ml/hr. The amount of viable cell was not less than 96%. The follow-up period was 12 months.
Skin involvement was assessed both clinically by changes in modified Rodnan skin score and histologically by light microscopy after hematoxylin and eosin (H&E) and Masson’s trichrome stain.
Results were also evaluated by serological features (ESR, CRP, γ-globulin, fibrinogen and ANA) and instrumental examination (spirography, EGDS with biopsy on collagen and echocardiography).
All patients who underwent HSCT demonstrated clinically improved in the Rodnan skin score from 18.45±5.18 in the first visit to 15.58±8.27, 13.14±7.00 and 10.66±4.39 after 3, 6 and 12 months respectively (p<0.01). Decrease of the skin score was accompanied by morphological changes in derma, that established a biodegradation process of fibrous tissue. Thus, the microscopy of derma before HSCT showed dystrophy with deposit of keratin, an atrophy of appendages and proliferation of the connective tissue. 12 months later microscopy revealed a proliferation of basal cells with small newly formed vessels and reduction of connective tissue fibers.
Moreover serological manifestations such as levels of ESR, CRP, fibrinogen, γ-globulin, ANA also decreased. E.g. CRP decreased from 9.04±2.19 to 2.20±0.67 mg/l after a period 12 months (p=0.02), the level of ESR had the same dynamic – from 25.39±7.95 to 18.81±6.72 mm/h (p=0.01). ANA declined to within the normal range.
Results analysis also demonstrated stabilization of lung function and significant improvement in pulmonary hypertension according to mean pulmonary artery pressure.
During 12 month we didn’t observed any complications of stem cell transplantation.
HSCT in patients with refractory systemic sclerosis has demonstrated decrease of skin fibrosis, improvement in serological markers, stabilisation of internal organ function and regression of fibrosis morphologically. These findings indicated HSCT appears beneficial in treatment of patients with SSc refractory to conventional treatment options.