Stem Cell Benefits Persist In Scleroderma Patients

ABANO TERME, ITALY — Autologous stem cell transplantation has produced durable benefits in a small series of patients with severe systemic sclerosis, based on 2 years of follow-up data, Dr. Irene Miniati reported at a congress on skin, rheumatism, and autoimmunity.

Rapidly progressive diffuse systemic sclerosis carries a poor prognosis, with an estimated mortality of 40%–50% at 5 years. Stem cell transplantation has emerged as a promising new approach to treatment, with the aim of providing a new immune system that can reacquire the self-tolerance lost in autoimmunity, Dr. Miniati said.

Four patients who had not responded to treatment with intravenous cyclophosphamide underwent the procedure; their mean age was 48.5 years, and they had a mean disease duration of 28 months. The protocol involved mobilization with cyclophosphamide plus granulocyte colony-stimulating factor, then apheresis, followed by conditioning with cyclophosphamide plus rabbit antithymocyte globulin. One additional patient was considered a mobilization failure because an adequate number of CD34+ stem cells could not be obtained during apheresis.

At baseline all patients had very high modified Rodnan skin scores, and all showed reduced carbon monoxide diffusion capacity (DLCO) on lung function tests. (See chart.) Two patients had mild to moderate pulmonary hypertension. High-resolution computed tomography revealed the presence of pulmonary fibrosis in three patients and ground glass areas in two, said Dr. Miniati of the University of Florence (Italy).

After the autologous stem cell transplantation, skin scores improved rapidly with the improvement persisting for at least 2 years. There also was a reduction in the ventricular-atrial gradient on Doppler echocardiography, stabilization of lung function, and improved quality of life as measured by the Health Assessment Questionnaire, she said.

None of the patients has developed opportunistic infections during the 2 years of follow-up. No arrhythmias occurred during the infusions, and despite concerns about cardiac toxicity with the administration of cyclophosphamide to patients with underlying cardiac injury, no toxicity has been seen.

Data on capillaroscopy patterns in these patients were covered in an abstract she presented at last year's meeting of the European League Against Rheumatism (EULAR), Dr. Miniati said in response to a question. Nailfold videocapillaroscopy (NVC) is a technique for visualizing and evaluating microvascular damage in scleroderma using an optical probe connected to image analysis software. NVC patterns have been classified as early, active, and late (Rheumatology [Oxford] 2004;43:719–26).

In Dr. Miniati's EULAR presentation, she reported that all four patients in her series showed a typical late pattern before stem cell transplantation, with few giant capillaries, large avascular areas, and vascular architectural disorganization. Three months after the transplantation, the NVC pattern had improved and was classified as active, characterized by numerous giant capillaries, hemorrhages, an absence of avascular areas, and disorganization of the normal capillary array with ramified/bushy capillaries. This pattern suggests angiogenesis and has persisted for 2 years (Ann. Rheum. Dis. 2005;64[suppl. 3]:289).