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Treatment of Children and Adolescents with Juvenile Rheumatoid Arthritis and Severe Systemic Lupus Erythematodes with High Dose Chemotherapy and Autologous Stem Cell Transplantation



Treatment of Children and Adolescents with Juvenile Rheumatoid Arthritis and Severe Systemic Lupus Erythematodes with High Dose Chemotherapy and Autologous Stem Cell Transplantation



Blood 100(11): Abstract No 5479, November 16



ASCT has been proposed as a new therapeutic option for patients with severe autoimmune disease refractory to conventional treatment. Here, we report three children with a severe form of systemic JRA and two patients with severe systemic lupus erythematodes treated with ASCT in a phase I study. Patients: Three patients (age: 5, 9, 14 yrs) who developed severe systemic JRA with high spiking fever, rashes, hepatomegaly, polyarthritis, morning stiffness, ESR > 100 mm/h, CRP > 100 mg/l were refractory to NSAIDs, MTX, cyclophosphamide, steroids, etanercept after 2.5, 13 and 6 yrs. 2 patients (age: 16, 20 yrs) with SLE had a disease duration of 2.5 / 5.5 yrs with arthritis, carditis, pericarditis, hypertonus, reduced pulmonary capacity, increased Anti-ds DNA titre. SLE was refractory to steroids, MTX, IVIG, CsA and cyclophosphamide (total doses: TPN 340: 14,2 g/m2; TPN 373: 6,2 g/m2). TPN 373 had a WHO class IV glomerulonephritis with a creatinine clearance of 52 ml/min nonresponsive to i.v. cyclophosphamide. Stem cell harvest: After a priming dose of cyclophosphamide (2-3 g/m2) and mobilization with G-CSF (10 mug/kg/day) peripheral blood stem cells were collected using of a Cobe separator. Using a Clinimacs device, CD34-positive selection was performed yielding a final CD34+ -cell amount of 4.2 - 11.9 x 106/kg contaminated with zero to 3.2 x 104/kg CD3+ lymphocytes, respectively. Stem cells were stored in liquid nitrogen. Conditioning regimen: Fludarabine (30 mg/m2): days -7 and -6; cyclophosphamide (50 mg/kg): days -5 to -2; ATG (5 -10 mg/kg): days -6 to -2; methylprednisolone (1g/m2): days -4 to -2. On day 0, the frozen CD34+ cells were thawed and infused. Results: All drugs but prednisolone were stopped before ASCT. Prednisolone was tapered and stopped 2 months after transplant. The conditioning of the patients with cyclophosphamide and G-CSF for CD34+ mobilisation was well tolerated without symptoms of reactivation of rheumatic arthritis and SLE. Rapid engraftment of neutrophils > 1.0 GPT/l: days +10 to +13; platelets > 20 GPT/l: days +6 to +19. Lymphocytes showed a tendency of normalisation during 5 months posttransplant in patients with JRA. One patient with SLE acquired on day + 45 EBV infection with LPD which was treated successfully with ganciclovir, cidofovir and rituximab. Patients were discharged from hospital on day + 24 to + 53 and remained free from active JRA and SLE with no immunosuppressive medication for 4, 17, 19, 29 and 29 months, respectively. CHAQ score showed a clear improvement at evaluation 6-12 months after ASCT. The SLEDAI scores decreased continuously (TPN 340: day +365: 0; TPN 373: day +115: 4). After a traumatic injury one patient with JRA developed a gonarthritis 17 months after ASCT without symptoms of her initial disease as spiking fever, rash, morning stiffness. Conclusion: ASCT is a possible new approach that offers hope to such patients.

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Accession: 035980366

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