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Autologous stem cell transplant for patients with diffuse systemic sclerosis (SSc), without selecting for a particular hematopoietic cell type, performed about as well in a new single-arm trial as was seen earlier with CD34+ stem cell transplant.

Three-quarters of the study's 20 patients survived 5 years without relapse or recurrence, and overall 5-year survival was 85%, according to George Georges, MD, of Northwestern University in Chicago, and colleagues.

Transplantation was far from problem-free, however: eight patients needed intensive care in the days following the procedure and two died from related complications, the group .

Patients with renal impairment fared the worst, Georges and colleagues noted. But for those with normal kidney function and no history of renal crisis, the procedure followed in the trial "appears to be a highly effective treatment" for SSc, albeit with a "moderate incidence of [intensive care unit] admission."

Stem cell transplant for diffuse SSc has become a hot topic insofar as conventional therapies, including biologic drugs as well as older immunosuppressants, have largely failed to deliver increased improved survival, Georges and colleagues observed (although a study reported earlier this year disputed that assessment). The condition often involves progressive organ dysfunction; a pegged the 10-year survival rate after diagnosis at 62.5% for all SSc forms.

Two transplant approaches have been tested in randomized trials, called Autologous Stem Cell Transplantation International Scleroderma () and Scleroderma: Cyclophosphamide or Transplantation (). Both showed substantial survival gains relative to conventional treatment with cyclophosphamide; however, SCOT also involved a myeloablative conditioning regimen and, in both studies, patients' peripheral blood stem cells (PBSCs) were processed to extract CD34+ cells for autologous transplant.

In the current study, called (Scleroderma Treatment With Autologous Transplant), Georges and colleagues used a non-ablative conditioning regimen and transplanted unselected PBSCs, to be followed by indefinite maintenance treatment with mycophenolate mofetil (MMF) or mycophenolic acid (MPA). Conditioning entailed cyclophosphamide at 200 mg/kg accompanied by horse anti-thymocyte globulin, similar to the ASTIS procedure. At months 2-4 after transplant, patients were placed on maintenance with target doses of 1,000 mg MMF or 720 mg MPA twice daily but titrated to tolerance.

Eligibility criteria included disease duration (from symptom onset) of 5 years or less and either lung/kidney involvement or rapidly progressive and extensive skin manifestations for no more than 2 years; they also had to have received at least 4 months of conventional treatment without benefit. Patients with severe pulmonary or cardiac impairment were excluded.

Participants ranged in age from 13 to 70, with a mean of 46. Fifteen were women. Most had been diagnosed within the previous 2 years. All but two had interstitial lung disease; in five, their estimated glomerular filtration rate (eGFR) was 75 mL/min/1.73 m² or less. Patients were followed for at least 5 years (excepting those who died earlier) and up to 11 years.

The two transplant-related deaths occurred 37 and 44 days after transplantation. Significantly, both had renal impairment, with eGFR values of 57 and 43 mL/min/1.73 m². For other patients needing intensive care, renal and/or pulmonary events were largely the immediate problems. One eventually required a kidney transplant. There was also one death occurring 8 years post-transplant: this patient developed myelodysplastic syndrome that progressed to acute myelogenous leukemia.

Overall, five participants incurred SSc relapse (four of whom survived to end of follow-up) and two developed organ failure (not counting the two who died early).

Adherence to the MMF/MPA maintenance was incomplete. Five patients never started it, and two discontinued within 2 years; another four had quit by year 5.

Still, every patient who remained event-free by month 3 had "stable or improved" kidney function, the investigators reported. Similarly, "available follow-up echocardiograms and electrocardiograms for the 14 patients with long-term EFS [event-free survival] were stable/unchanged."

Also, among the 18 patients surviving the transplant, two-thirds showed at least 50% sustained reduction in skin involvement. Certain autoantibody species disappeared in a minority of participants, although Georges and colleagues noted that "a clinically favorable response to transplant did not require conversion to seronegativity."

The investigators concluded that the conditioning regimen was probably "too toxic" for patients with low eGFR values. They were also uncertain whether their non-myeloablative regimen was actually superior to the ablative procedure used in SCOT, which incorporated total body irradiation. Georges and colleagues observed that the latter might be less immediately toxic, but they had decided not to include it because of the risk for secondary malignancies. That could be revisited, they suggested.

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