Background/Purpose

In the recent years, autologous haematopoietic stem cell transplantation (AHSCT) has been shown to represent an effective therapeutic option for patients (pts) suffering from rapidly progressive SSc, although the number of available clinical trials at present is relatively scant. Aim of the study was to retrospectively evaluate the efficacy of AHSCT in a long term in a number of patients with severe diffuse cutaneous SSc after a long lasting period of observation.

Methods

Since 2003, 18 pts  affected by diffuse cutaneous SSc (male 5, female 13; median age 40 years, range 20 – 62), underwent AHSCT using positively selected CD34+ cells. Pts were eligible if they had a rapidly progressive disease, a modified Rodnan Skin Score (mRSS) > 14 and a clinical activity score > 3 (evaluated according to the European Scleroderma Study Group – ESSG), in the absence of major organ involvement. Mobilisation was performed with CTX 4000 mg/m2 given over two days and G-CSF 10 μg/m2/day. Conditioning regimen included CTX 50 mg/kg/day on days -5 to -2 and rabbit ATG 2.5 mg/kg/day on days -3 to -1. The major outcome variables were treatment safety and clinical response, in terms of mRSS and ESSG improvements. The long-term follow-up of organ disfunction was evaluated by echocardiographic LEVF or PAPs, and functional respiratory parameters DLCO and VC.

Results

The median follow-up was of 37 months (range 6–138). Ninenty-four % (17/18) of the pts demonstrated a beneficial clinical response with significant reduction of mRSS > 30% and ESSG at Month 6,  and a further reduction of mRSS at year 1 of the most part of them was observed.

The mean mRSS was 19.8 (SD + 5.3) at baseline, 9.3 + 4.6 at Month 6, 6.21 + 7.4 at year 1 and 3.0 + 2.2 at year 5; all the reductions were statistically significant ( < 0.001). The mean ESSG was 5.3 + 0.85 at baseline, 2.1 + 0.8 at Month 6, 2.0 + 1.6 at year 1 and 1.5 + 0.96 at Year 5; all the reductions were statistically significant (p< 0.0001). Organ involvement was nearly unchanged during follow-up: mean value of DLCO at baseline 65.0% + 19%, at Year 1 67.2% + 17.8% and at Year 5 58.0% + 14.7% (p=ns); mean value of VC at baseline 81% + 23.6%, 82% + 15.7%, 89.2% + 26% (p=ns). No echocardiographic changes were identified during follow-up. Two patients died during follow-up of SSc from pulmonary and cardiac complications due to the disease. One patient died from interstitial pneumonia at day + 65, leading to a TRM of 5.6% (1/18).

Conclusion

Conclusion: This study confirms that AHSCT in selected patients with  rapidly progressive SSc results in sustained improvement of skin thickening and stabilisations of organ function up to 10 years after transplantation, so leading to a global clinical improvement, as showed by the persistent reduction in the ESSG clinical activity score. According to other experiences, TRM resulted reasonable, as a possible result of patients selection. These finding are in keeping with the view that AHSCT is effective in improving the active phase of SSc, while letting unchanged and stable the fibrosclerotic one. Further studies are needed to evaluate the importance of CD34 selection, the need of immunosuppressive therapy post-AHSCT and the best timing of HSCT in the treatment of SSc patients.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/efficacy-of-autologous-hematopoietic-stem-cell-transplantation-in-rapidly-progressive-systemic-sclerosis-prolonged-remission-of-disease-activity-in-a-long-term-follow-up/