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Autologous stem cell transplantation for juvenile idiopathic arthritis

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Between 5% and 10% of children with systemic or polyarticular onset juvenile idiopathic arthritis (JIA) do not response adequately to treatment with non-steroidal antiinflammatory drugs and immunosuppressive drugs such as methotrexate and corticosteroids. Among such children severe joint destruction, growth retardation, drug toxicity, and psychological distress are common and some (around 2–4% of children with systemic onset disease) die of the disease. The main causes of death are drug toxicity, infection, amyloidosis, and the later development of diseases such as systemic lupus erythematosus or scleroderma. Anti-tumour necrosis factor (anti-TNF) treatment has proved effective for children with polyarticular onset disease but less so in those with active systemic onset disease.

If standard immunosuppression is effective treatment for most children with JIA then perhaps intense immunosuppression and autologous stem cell transplantation (ASCT) would be effective for children with more severe, refractory disease? Since 1997, 41 children in Europe are known to have had ASCT for refractory polyarticular or systemic onset JIA. The findings on follow up of 34 of these children at nine European centres have been reported (

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There were 19 boys and 15 girls. Their mean age at disease onset was 3 years 11 months (range 8 months to 10 years 2 months) and at ASCT 9 years 5 months (range 4 years 3 months to 18 years 3 months). Twenty-nine had systemic onset and five polyarticular onset JIA. Ten had been treated unsuccessfully with anti-TNF therapy. All had delayed growth and 27 had osteoporosis. Other evidence of drug toxicity included hypertension, myelosuppression, vertebral fractures, avascular necrosis of the femoral head, and cataracts.

All 34 children had successful engraftment with full haematological recovery. Three children died as a result of transplantation, at 10 days, 18 days, and 4 months post ASCT. Posttransplant morbidity included infection (24 children, 6 with septicaemia), varicella-zoster virus infection (11 patients at 3–18 months), and cytomegalovirus infection (6 reactivation, 1 primary, at 1–12 months). The mean duration of follow up at the time of reporting was 2 years and 4 months. Eighteen children had complete drug-free remission of their disease, six had a partial response, and seven had no lasting response. Among the patients who eventually achieved complete remission there were five whose disease got worse when prednisone dosage was tapered at 3–6 months. These flare-ups responded to standard management. The seven patients classified as non-responders all improved soon after ASCT but their JIA relapsed after 3–17 months. The six patients with a partial response were more responsive to standard treatments after transplantation. Two achieved 30% improvement, three 50%, and one 70%. Wellbeing and pain scores generally improved greatly in the first 3-6 months and improvement was maintained.

ASCT induced drug-free remission in over half of these children with severe, refractory JIA and substantial improvement in another six of the 34. Marked increase in general wellbeing was noticeable. Three children died and posttransplant morbidity was common. It is proposed that in future total body irradiation will not be used as part of the conditioning regimen and antiviral drugs and intravenous immunoglobulin will be given prophylactically until the CD4+T cell count is normal.

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