The role of autologous haemopoietic stem cell transplantation in the treatment of autoimmune disorders.

Autologous haemopoietic stem cell transplantation (HSCT) has been used for over 30 years for malignant haematological diseases, such as myeloma and lymphoma, with considerable success. More recently this procedure has been adopted as a form of high dose immunosuppression in selected patients with autoimmune diseases that are resistant to conventional therapies. Animal models have previously outlined the rationale and validity of HSCT in patients with these non-malignant, but in many cases, life-threatening conditions. Recent data have that deletion of putative autoreactive immune clones with reconstitution of a thymic driven, tolerant immune system occurs in HSCT for auto-immune patients. Two randomised control trials have confirmed that HSCT is superior to monthly cyclophosphamide in systemic sclerosis with a highly significant disease free and overall survival benefit demonstrated in the Autologous Stem cell Transplantation International Scleroderma trial. Over 2000 patients worldwide with autoimmune conditions have been treated with HSCT - the commonest indications being multiple sclerosis (MS) and systemic sclerosis. Encouraging relapse free survival of 70-80% at 4 years, in heavily pre-treated MS patients, has been demonstrated in Phase II trials. A Phase III trial in MS patients who have failed interferon is currently accruing patients. Future challenges include improvements in safety of HSCT, particularly in cardiac assessment of systemic sclerosis patients, cost-benefit analyses of HSCT compared to standard therapy and establishment of centres of excellence to continue to enhance the safety and benefit of this exciting new therapy.

Potentially preventable tuberculosis among HIV-infected persons in the era of highly active antiretroviral treatment.

OBJECTIVE: To characterize the proportion of tuberculosis (TB) cases that could have been prevented among human immunodeficiency virus (HIV) infected persons receiving care in the era of highly active antiretroviral treatment (HAART). DESIGN: We conducted an observational cohort study among HIV-infected patients with >or=2 out-patient visits at the Comprehensive Care Center, Nashville, Tennessee, USA, between 1 January 1998 and 31 December 2005. METHODS: A potentially preventable TB case was defined as a case in which the patient received no screening tuberculin skin test (TST) prior to TB diagnosis or a case in which a patient with a positive screening TST did not complete treatment for latent infection. RESULTS: Of 3601 HIV-infected persons in care (13 905 person-years [p-y] of follow-up), 29 developed TB (230/100,000 p-y). Of the 29, 20 (69%) had not had TST performed as part of routine screening. Of the nine patients screened, four had a positive test, three of whom completed treatment for latent TB infection. Of 29 TB cases, 21 (72%) were therefore potentially preventable. CONCLUSIONS: Most TB cases in this cohort were potentially preventable had the patients undergone a screening TST followed by treatment of latent infection if they had a positive TST.