Autologous Hematopoietic Stem Cell Transplantation without Total Body Irradiation for Diffuse Scleroderma. Rapid Improvement of Skin Score.

Background & Aims Scleroderma is an immune mediated vasculopathy of unknown etiology. There is no known therapy that could alter the natural course of the disease. Patients with diffuse cutaneous disease or visceral involvement has an overall 10-year survival of 35 to 68%. Hematopoietic stem cell transplantation (HSCT) has been performed in the US, but with substantial toxicity, may be due to regimens that utilize total body irradiation (TBI). We performed autologous HSCT without TBI. Methods We conducted a phase I HSCT study in 5 patients with diffuse scleroderma with poor clinical features. Candidates were less than 65 years old with modified Rodnan skin score (mRSS) of more than 14 or lung diffusion capacity (DLCO) less than 80%, interstitial lung disease, elevated ESR, renal involvement, or abnormal electrocardiogram. 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 not manipulated. The conditioning regimen consisted of 200mg/kg cyclophosphamide (CY), and 7.5mg/kg rabbit antithymocyte globulin (ATG). Results The procedure was well tolerated with anticipated cytopenias, neutropenic fever, and fluid overload that were easy to manage and without mortality. The median days for neutrophil and platelet engraftment were 8 (range 7–9) and 8 (range 0–10), respectively. The median infused CD34+ and CD3+ cell counts were 9.27 x 106/kg (range 2.35–14.7) and 2.34 x 108/kg (range 1.48–6.83), respectively. Improvement of mRSS and changes of pulmonary function {DLCO, total lung capacity (TLC)}, cardiac function {left ventricular ejection fraction (LVEF), pulmonary artery pressure (PA pressure)} and renal function (creatinine) pre-HSCT, at 6 months and at 12 months post-HSCT are in table 1. After median follow-up of 19 months (range 8–20), all patients had improvement of skin score while pulmonary, cardiac and renal function remained stable. Conclusion Autologous HSCT with CY/ATG is safe and may be effective. Randomized studies will be needed to confirm the efficacy of this therapy. table 1 | patient | | skin score (mRSS) | DLCO % | TLC % | LVEF % | PA pressure mmHg | Creatinine mg/dl | |:------- | --------- | ----------------- | ------ | ----- | ------ | ---------------- | ---------------- | | 1 | pre HSCT | 26 | 48 | 71 | 60 | 23 | 0.7 | | | 6 months | 13 | 39 | 73 | 63 | normal | 0.7 | | | 12 months | 6 | 44 | 74 | 64 | 20 | 1 | | 2 | pre HSCT | 31 | 86 | 114 | 58 | 33 | 0.7 | | | 6 months | 17 | 62 | 106 | 60 | unable to obtain | 0.8 | | | 12 months | 17 | 118 | 112 | 60 | 28 | 1 | | 3 | pre HSCT | 31 | 57 | 73 | 70 | 36 | 0.8 | | | 6 months | 18 | 55 | 64 | 60 | 35 | 0.7 | | | 12 months | 18 | 48 | 69 | 65 | 43 | 0.7 | | 4 | pre HSCT | 24 | 59 | 83 | 55 | unable to obtain | 0.5 | | | 6 months | 8 | 52 | 79 | 55 | 26 | 0.5 | | | 12 months | 5 | 45 | 73 | 50 | unable to obtain | 0.4 | | 5 | pre HSCT | 30 | 48 | 94 | 55 | 25 | 0.6 | | | 6 months | 8 | 54 | 80 | 55 | normal | 0.7 |