The concept of hematoimmunoablation followed by autologous hemopoietic stem cell transplantation (HSCT) as a treatment for severe autoimmune disease has gained momentum in the past several years. Almost from the beginning, international consensus was reached concerning principles of patient selection and treatment regimens, and several phase-I and -II pilot studies were commenced. It was also agreed to collect as much data as possible following mobilisation in order to develop a databased risk assessment of the procedure and later to balance this against benefit. Under the auspices of the EBMT and EULAR, a database was established, which was later extended to include Australian and US cases. The current database includes over 150 cases and has been presented in several forums. In addition, the IBMTR contains similar cases and case reports, and small series have been published. The majority of cases have been MS, followed by scleroderma (systemic sclerosis or SSc), RA, juvenile arthritis, SLE, and others.
A preliminary analysis of the international data base showed a transplant-related mortality of 9%, comparable to that seen in a group of lymphoma patients treated in the EBMT centres over the same period (6%). So far, no fatalities have been published in the literature.
Several issues have emerged as the experience grows. The most important is patient selection and exclusion. The original loose guidelines of `potentially sick enough to justify the risk but not too severe to be either irreversible or too ill for the treatment' have proven difficult to quantify. Potential disease-specific aspects contribute to transplant-related mortality (eg cardiac involvement in SSc and cyclophosphamide toxicity) and to transplant-related problems (eg age of patient and general medical condition). The unwanted events have been generally consistent with previous BMT experience, with the possible exception of mobilisation complications in SSc.
Several subgroups have been formed under the auspices of the EBMT to look at disease-specific aspects in SSc, RAS/JCA, MS, and SLE/vasculitis, and these findings will be published.
Concerning mobilisation-related events, a suggestion of growth factor-related autoimmune disease (AD) flare is subject to a separate ongoing study. The current feeling is that in systematically active AD, such as Still's disease, SLE, and vasculitis, cyclophosphamide should be given prior to growth factor until more data are available. Only a few patients have experienced failed mobilisation, and this was successful at second mobilisation in most.
No conditioning regimen has so far proven superior with respect to remission induction and/or maintenance. Regimens have mostly followed published guidelines, with a suggestion of more infectious complications following heavy T-cell purging.
Efficacy has ranged from dramatic to none and death from disease progression. In general, outcome measurement has not been standardised between groups but is well defined within the individual centres. Around two thirds have been reported as `improved or stabilized,' and more data are required, including relapse rates and severity.
Data collection is critical, with a current liaison group working toward standardising MED A and MED B equivalent data collection in Europe and the US. In particular, standardised measurements of immune or B-cell phenotype in peripheral blood has been associated with successful or unsuccessful outcome. As predicted, heavy T-cell purging was associated with more prolonged T-cell CD4-penia and increased infection. This is also subject to a subgroup working party. Eventually, the final place of such a treatment, if it exists, will be established through prospective comparative trials.