WASHINGTON, DC—Non-myeloablative hematopoietic stem cell transplantation may be a safe and effective treatment option for patients with severe scleroderma and should be studied further, according to researchers who presented phase I safety data at the 70th Annual Meeting of the American College of Rheumatology (ACR) in Washington, DC.¹

Richard K. Burt, MD, and colleagues from Northwestern University Medical Center in Chicago reported that although two of 10 patients with severe scleroderma relapsed in skin scores after the stem cell transplantation, eight of 10 remain progression-free, and some have continued to improve beyond 3 years.

"We never use the word cure, but to see a reversal in skin and organ damage is encouraging. [However], we don't know what will happen in the long run to these patients," Dr. Burt said.

Cure for scleroderma?

The 10 patients in the study were treated with a "reduced intensity" lymphoablative regimen of 200 mg/kg cyclophosphamide and 7.5 mg/kg rabbit antithymocyte globulin (rATG) after peripheral blood stem cells had been mobilized with cyclophosphamide and granulocyte colony-stimulating factor, harvested, and cryopreserved without manipulation. The median number of infused CD34+ cells was 7.38 x 106/kg. The median number of infused CD3+ cells was 2.14 x 108/kg.

At the study's inception, patients had modified Rodnan skin scores greater than 14 and were aged 26 through 56 years. Patients had a disease duration spanning 10 to 56 months; most had interstitial lung involvement, and almost all had electrocardiogram abnormalities.

Following re-infusion of the harvested stem cells, most patients showed significant softening of skin and improvements in modified Rodnan skin scores. Moreover, there were no transplant-related deaths and no changes in ejection fraction, pulmonary artery pressure, or renal function.

On average, patients remained in the hospital for 2 to 3 weeks. Neutrophil and platelet engraftment both occurred a median of 9 days after stem cell infusion.

Five patients developed fever, but there were no cases of sepsis reported. One patient died of complications related to scleroderma. That patient had advanced disease and poor performance status before transplant, had improved skin scores after transplant, but died in a nursing home 2 years after transplant.

"These results are encouraging for visceral organ function," Dr. Burt said.  "We have had patients with locked elbows who were able to straighten them out to normal."

Two patients had recurrence of skin thickening (at 12 and 24 months after transplant). After initiation of mycophenylate mofitel treatment, one patient's skin problems stabilized and the other patient's improved.

Lead study author Walter G. Barr, MD, professor of rheumatology at Northwestern University Medical School, said he was encouraged by the results, adding that the next step is a randomized controlled trial.

Light approach focuses on safety

Comparing the current trial to the Scleroderma: Cyclophosphamide Or Transplantation (SCOT) study, Dr. Burt pointed out that the SCOT study uses myeloablative radiation and CD34 selection. "We broke away from the SCOT trial because of radiation," Dr. Burt said. He said that to date, researchers at Northwestern have treated 170 patients with this regimen, with a mortality rate of 1.3%. "We'd like it to be zero, but the point is that this can be done with low mortality," he said.

"If we can show that this is an effective therapy with reasonable morbidity and mortality, it is something we will shoot for," Stanley B. Cohen, MD, professor of medicine, Southwestern Medical School, University of Texas, in Dallas, told CIAOMed. "This is a horrible disease."

In conclusion, Dr. Cohen noted that questions remain regarding which patients make the best candidates for this therapy.


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