Japanese researchers report promising phase I–II trial results showing that high-dose cyclophosphamide (CY) supported by autologous peripheral blood stem cell transplantation (PBSCT) is feasible and may be effective in the treatment of severe and refractory autoimmune diseases including systemic sclerosis (SSc), systemic lupus erythematosus (SLE), amyopathic dermatomyositis (ADM) and Wegener's granulomatosis (WG). The new findings appear in the August 26, 2005, online first edition of the Annals of Rheumatic Disease.¹

No treatment-related mortality

Researchers mobilized peripheral blood stem cells (PBSCs) during hematologic recovery after relatively high-dose CY (2 g/m² for 2 days) followed by administration of granulocyte colony stimulating factor (G-CSF). After collecting PBSCs (>e;2x10⁶ CD34+cells/kg) by apheresis, CD34+ cells were immunologically selected and cryopreserved. According to the new findings, hematopoietic reconstitution was "rapid and sustained."

While regimen-related toxicity included various infections such as pneumonia, sepsis, cystitis, herpes zoster, and acute heart failure, there was no treatment-related mortality.

 

Specifically, sclerosis of the skin was markedly improved in all 6 patients with SSc. Researchers noted significant improvement  among SSc patients when interstitial pneumonia (IP) was evaluated by PaO₂, serum KL-6 levels, and pulmonary high-resolution computed tomography. In a patient with ADM, severe and progressive IP was also markedly improved. In a patient with WG, the size of the left orbital granuloma decreased substantially, resulting in reduction of the exophthalmos.

 

"We have first demonstrated the clinical effects of high-dose CY with autologous PBSCT on IP of SSc and on granuloma of WG," conclude the researchers, led by Hiroshu Tsukamoto, MD, of the Kyushu University Graduate School of Medical Sciences in Fukuoka, Japan. "A prospective study with longer follow-up time and more patients will be necessary to assess the efficacy of this treatment modality in the treatment of autoimmune disease."

Steven Pavletic, MD, head of the Graft-versus-Host and Autoimmunity Unit of the Experimental Transplantation and Immunology Branch at the National Cancer Institute in Bethesda, Maryland, points out that this is another study demonstrating the "already well documented safety and impressive therapeutic potential of autologous transplantation in patients with severe autoimmune disease, in this case systemic sclerosis. [Because] there are so few therapies with effect on fibrotic processes, these results are even more important," he tells CIAOMed.

Going forward, a National Institutes of Health–sponsored US multicenter randomized trial for SSc that was initiated this year should give the definitive answer to the question of how this treatment compares to conventional approaches, he says.

Still, Dr. Pavletic cautions, "without active engagement of rheumatologists nationwide in identifying and referring patient candidates to the transplant centers who participate in this trial, we will not be able to address the question of whether autologous transplantation should become a standard therapy for patients with severe and refractory systemic sclerosis."

Stem cell transplantation shows promise in severe, refractory RA

CIAOMed recently reported promising results on new research that helps delineate some of the benefits and potential limitations of high-dose chemotherapy followed by autologous hematopoietic stem cell transplantation in patients with severe refractory rheumatoid arthritis.

The new study, released in Arthritis & Rheumatism,² followed eight transplant patients for 5 years. According to the findings, improvements in functionality and health status were most marked during the first 9 months after transplantation and lasted up to 2 years.

References

1.  Tsukamoto H, Nagafuji K,  Horiuchi T, et al. Phase I–II trial of autologous peripheral blood stem cell transplantation in the treatment of refractory autoimmune disease. Ann Rheum Dis Online. Published August 26, 2005.

2. Teng YK, Verburg RJ, Sont JK, et al. Long-term follow-up of health status in patients with severe rheumatoid arthritis after high-dose chemotherapy followed by autologous hematopoietic stem cell transplantation. Arthritis Rheum. 2005;52:2272-2276.