Autologous Non-Myeloablative Hematopoietic Stem Cell Transplantation for Refractory Systemic Vasculitis.

Background Current mortality rate in systemic vasculitis (SV) patients with the use of cytotoxic / immunosuppressive therapy is over 20 % at 5 years in some studies. For patients refractory to conventional therapy new strategies aimed at aggressive induction of remission and relapse prevention are being sought. We here report our single center experience in treating 4 patients with refractory SV employing non-myeloablative autologous hematopoietic stem cell transplantation (HSCT). Patients and Methods Four patients with refractory SV (2 - with neurovascular Behcet’s disease, 1 - with neurovascular Sjogren’s syndrome, and 1 - with Wegener’s granulomatosis) were involved in an IRB and FDA approved phase I clinical trial of high dose chemotherapy and autologous HSCT. Peripheral blood stem cells were mobilized with cyclophosphamide (Cy) 2g/m2 IV and granulocyte-colony stimulating factor 10 mcg/kg/day SQ and were CD34+ enriched. Conditioning regimen consisted of Cy 200 mg/kg and rabbit anti-thymocyte globulin 5.5 mg/kg IV. Disease activity and cumulative organ damage were assessed using Birmingham Vasculitis Activity Score (BVAS) and Vasculitis Damage Index (VDI), respectively. Primary and secondary endpoints were transplant-related toxicity, survival and change in BVAS and VDI after the transplant. Results All 4 patients tolerated HSCT well without transplant related mortality or any significant toxicity. At median follow up of 28 (range 22–35) months all patients are alive. Three patients (1 each with Behcet’s, Sjogren’s, and Wegener’s) entered a sustained remission at 6, 6 and 24 months after the transplant. Both, BVAS and VDI, markedly decreased within 6 months post-transplant. In a patient with WG C-ANCA levels became undetectable at 24 month evaluation corresponding to clinical and radiological improvement. All 3 patients who achieved remission discontinued immunosuppressive therapy at the time of transplant and have not required since. Two patients with pre-transplant steroid dependency discontinued prednisone at 6 and 14 months after HSCT. One patient with BD who is positive HLA-B51, now 22 months since HSCT, has never achieved remission and is still requiring immunosuppressive therapy. Conclusion We suggest autologous HSCT utilizing a non-myeloablative regimen is a safe and effective treatment for select patients with SV refractory to conventional immunosuppressive therapies. However, in patients with significant genetic predisposition, more aggressive approach such as allogeneic HSCT or cord blood transplantation might be considered.