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FRI0003 High dose chemotherapy without autologous stem cell reinfusion in the treatment of ra
  1. KD Pile,
  2. M Rischmueller,
  3. L Milazzo,
  4. W Jaksic,
  5. N Wickham
  1. Departments of Rheumatology and Haematology, Adelaide University Department of Medicine, TQEH, Adelaide, Australia

Abstract

Background With increasing use of high dose cytotoxic chemotherapy with autologous peripheral blood stem cell (APBSC) rescue for the treatment of severe autoimmune diseases, including RA, there is concern that the reinfusion of auto-aggressive T cells may reactivate the autoimmune process. High dose chemotherapy without the reinfusion of autologous stem cells permits a form of in vivo T cell depletion and stem cell selection that obviates the reinfusion of auto-aggressive T cells.

Objectives Evaluation of medium term outcome in patients undergoing high dose chemotherapy without autologous stem cell reinfusion in patients with severe RA.

Methods Three patients with RA and one with JRA, which was progressive and severe despite multiple DMARDs, were treated with Cyclophosphamide 50 mg/kg for four consecutive days, with G-CSF 300 mcg bd commencing from day five. Prior to this, APBSC were collected following priming with Cyclophosphamide and G-CSF. The APBSC were not intended for reinfusion unless prolonged cytopenias or severe infection occurred. DMARDs were discontinued at the time of high dose chemotherapy and low to moderate dose prednisolone was commenced in all patients. Immunophenotyping of lymphocyte subsets was performed to monitor immune regeneration.

Results High dose cyclophosphamide was well tolerated and all patients achieved haematological recovery without the need for APBSC reinfusion. Median time to neutrophil recovery (ANC >500/(L) and platelet transfusion independence was 17 and 16 days, respectively. All patients required antibiotics for neutropenic fever for between 2 – 8 days.

Absolute change and% change from baseline at 6 and 12 months is shown in the Table 1. All subjects have required recommencement of a DMARD between 6 and 12 months post therapy. One patient, who had been taking long term oral steroids, developed bilateral avascular necrosis of the femoral heads.

Abstract FRI0003 Table 1

Absolute and% change from baseline at 6 and 12 months post therapy (< 100% equals% improvement).

Conclusion Whilst high dose chemotherapy without stem cell reinfusion may be considered as a therapeutic option in cases of severe progressive rheumatoid arthritis, further research in maintaining the initial benefit is required.

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