Autologous Hematopoietic Stem Cell Transplantation in Refractory Systemic Vasculitis Involving Central Nervous System.

Background & Aims

Systemic vasculitides (SV) are a subset of vasculitis with significant morbidity and mortality. They are considered as systemic autoimmune diseases that affect entire organ systems. The main stay of the therapy is immunosuppressive drugs including corticosteroids and cyclophosphamide, but some cases do not respond and their 5-year mortality can be as high as 42%. Hematopoietic stem cell transplantation (HSCT) has been performed in various autoimmune diseases with dramatic success, but reports in SV are limited. We performed herein the systemic series of autologous HSCT for SV with central nervous involvement.

Methods

We conducted a phase I HSCT study in 3 patients with SV (one with Neuro-Behζet’s disease, one with neurovascular Sjögren’s syndrome, one with central nervous system Wegener’s granulomatosis). All patient failed conventional corticosteroids, cyclophosphamide and intravenous immunoglobulin or plasmapheresis and still had active disease manifestations as following. (1) Behζet’s: recurrent cognitive deficits due to recurrent multiple microinfarcts and findings consistent with central nervous system vasculitis on magnetic resonance angiogram. (2) Sjögren’s: recurrent visual loss and paraparesis due to recurrent optic neuritis and transverse myelitis. (3) Wegener’s: severe right exophthalmos, visual disturbance and pain in the orbit and sinus due to a mass in right orbit and on clivus. Candidates were less than 60 years old with established diagnosis of SV including Wegener’s granulomatosis, polyarteritis nodosa, Churg-Strauss syndrome, microscopic polyangitis, neurovascular Sjögren’s syndrome or neuro-Behζet’s disease and must have progressive or recurrent neurologic deficits or progressive organ dysfunction {FFS (five-factor scale) >2 or BVAS (Birmingham Vasculitis Activity Score) >20} despite conventional therapy. Patients with irreversible end-stage organ involvement were excluded. Peripheral blood stem cells were mobilized with cyclophosphamide and granulocyte colony-stimulating factor. The graft was CD34 enriched with Isolex 300i®. The conditioning regimen consisted of 200mg/kg cyclophosphamide (CY), and 5.5mg/kg rabbit antithymocyte globulin (ATG).

Results

The procedure was well tolerated with anticipated cytopenias, and neutropenic fever. The median days for neutrophil and platelet engraftment were 10 (range 9–13) and 10 (range 9–11), respectively. The median infused CD34⁺ and CD3⁺ cell counts were 2.71 x 10⁶/kg (range 2.52–12.46) and 2.91 x 10³/kg (range 1.47–9.84), respectively. One patient with Sjögren’s developed a temporary flare-up after engraftment that resolved quickly after treatment with intravenous corticosteroids and subsequently has been in remission. Otherwise, there has not been any significant post-HSCT complication. The neuro-Behζet patient entered into remission 6 months post-HSCT and has remained in remission 11 months post-HSCT. The neurovascular Sjögren’s patient has been free of symptoms except residual small chronic scotoma in one eye 4 months post-HSCT. The Wegener’s patient achieved a complete improvement of exophthalmos, visual disturbance and pain 2 months post-HSCT.

Conclusion

Autologous HSCT with CY/ATG for SV is safe and effective. A longer follow up is needed to confirm its curative potential.