Stem Cell Transplantation for Severe Systemic Sclerosis

Very few treatments are effective in severe systemic sclerosis. Thus, any good news is highly welcome. A study[1] from the Netherlands presented at the American College of Rheumatology Scientific Sessions suggested that stem cell transplantation is beneficial for patients with severe systemic sclerosis. The conclusion that "This EMBT/EULAR database analysis shows durable responses in two thirds of patients up to three years after HSCT," projecting five-year probability of survival at 72%, is potentially very exciting.

The abstract, however, is misleading. Very few data about the patients are given in the abstract itself. Although 57 patients entered the study, only 10 were studied out to 3 years. In fact, the number of patients available at time points of interest was as follows:

Although the authors speak of 64% partial remission and 28% complete remission (in 50 patients), the denominator must apply to patients followed for less than six months, at which time they are barely getting through the preparation therapy. Scleroderma is a very chronic and progressive illness. As presented (recognizing that the full details are not available in the abstract), with such short follow-up, the conclusions do not appear to be justified.

In addition, there is no hint of a control group; in fact, this is an open label study and therefore very suspect. Although the skin responses are commented upon, many scleroderma patients undergo regression of their skin lesions without treatment over time. The authors note that no significant changes were observed in pulmonary or renal function, two organ systems in which life-threatening disease might justify such a drastic treatment.

Further, 13 of the 57 patients died, of whom five died of treatment-related causes and eight of disease. The author notes that stem cell transplantation "incurs considerable TRM," meaning transplant-related mortality, and suggests that control studies be done.

This reviewer remains skeptical about the value of stem cell transplantation in the face of such severe toxicity. When the full article is available, clear demonstration that the studied patients were sufficiently ill that high morbidity and mortality is justified may make this a potentially more interesting treatment. In addition, true survival curves demonstrating sustained response beyond five years will be necessary to bring this sort of treatment to the marketplace.