Intense Immunosuppression and Stem-Cell Transplantation for Patients With Severe Rheumatic Autoimmune Disease: A Review

Jacob M. van Laar, MD, Alan Tyndall, MD


Cancer Control. 2003;10(1) 

In This Article

Systemic Lupus Erythematosus

With its wide array of serum autoantibodies, linkage to genes encoding complement activation and apoptosis, and responsiveness to immunosuppressive medication, SLE is the prototype multisystem autoimmune dis-ease. The prognosis of lupus patients has improved with the introduction of corticosteroids and cyclophosphamide pulse-therapy for nephritis and central nervous system involvement. Nevertheless, some patients do not respond to this therapy and need renal replacement therapy in case of renal failure. Chronic immunosuppressive treatment and intrinsic immune abnormalities account for the high number of infectious complications observed in patients with severe lupus. At the time of this writing, 23 SLE patients treated with intensive immunosuppression and SCT have been reported so far, most as case reports or in small series.[51,52,53,54] The majority of patients received conditioning with cyclophosphamide (200 mg/kg) and ATG. Disease activity was significantly decreased in all patients after conditioning, but 8 patients needed immunosuppressive medication again after transplant. Six of 13 patients with renal involvement improved, and another 4 regained normal kidney function. One patient died after mobilization from disseminated mucormycosis. In the patient with the longest follow-up, reappearance of serum autoantibodies preceded renal relapse after a 3-year corticosteroid-free remission. High-dose cyclophosphamide (200 mg/kg) without stem-cell rescue has been successfully used in a small cohort of lupus patients.[55] This regimen was well tolerated and no serious adverse events were recorded, despite prolonged thrombocytopenia. A number of patients in this cohort had not previously been treated with standard pulse-therapy cyclophosphamide, however, and it remains to be established that similar responses can be attained in patients with refractory disease.

Of the 51 patients registered in the EBMT/EULAR database, disease manifestations at baseline involved kidneys (27 patients), central nervous system (21), skin (31), joints (23), hematologic abnormalities (24), vasculitis (9), serositis (6), lungs (9), peripheral nervous system (2), and other (10), reflecting its multisystem character. Investigators reported that 27 of the patients improved, 14 improved initially and then relapsed, and 7 died. Of the 7 deaths, 5 were considered transplant related (2 of septicemia, 1 of thrombotic thrombocytopenia, 1 of bleeding complication, and 1 of secondary leukemia), while 1 patient died of progressive disease (bronchiolitis obliterans) and another as a result of an accident. Thus, the treatment-related mortality in this cohort was 11% (95% confidence interval, 2%-20%).


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