Background/Purpose: Systemic sclerosis (SSc) comprises diverse clinical phenotypes with variable disease courses. Some SSc patients take miserable and fatal clinical course due to rapid progressive skin sclerosis and organ fibrosis in spite of intensive treatments. Establishment of effective therapy for severe SSc has been awaited. Autologous hematopoietic stem cell transplantation (HSCT) enables the patients to be given enough high dose of cyclophosphamide (CY) to delete autoreactive lymphocytes and lead to normal immune reconstruction. A randomized clinical trial showed HSCT led SSc patients to longer event-free survival than conventional CY therapy, however, HSCT has limited evidence on its feasibility and long-term efficacy for patients with severe SSc.

Methods: We conducted a phase II clinical trial approved by the local ethics committee. Patients with SSc diagnosed within the last three years and the following clinical features were included: rapidly progressive diffuse skin sclerosis, refractory digital ulcer, or interstitial lung disease. Patients over 60 years with severe organ failure were excluded. The mobilization regimen comprised intravenous CY (4 g/m²) and recombinant human granulocyte colony-stimulated factor. HSCT was performed after treatment with intravenous CY (200 mg/kg, divided into four days). We used the modified Rodman total thickness skin score (mRTSS) to assess the improvement of skin sclerosis. Good response was defined as more than a 50% decrease in mRTSS from baseline within six months after HSCT. Pulmonary function was also evaluated using spirometry, high resolution CT, and serum KL-6 level.

Results: Between 2000 and 2012, 15 patients who met the criteria and signed the informed consent were enrolled in the trial and 14 patients were given HSCT; one was not transplanted because of her mobilization failure. Median follow-up period was 137 months. Eight patients (57%) showed a good response to HSCT in the improvement of skin sclerosis, but skin sclerosis relapsed in two patients and interstitial lung disease progressed in another patient. Five patients (36%) kept a long-term efficacy of HSCT. Four in six patients without a good response to HSCT required additional treatments due to progression of diffuse skin sclerosis or interstitial lung disease. Adverse effects related to HSCT occurred in five patients (36%). Engraftment syndrome developed in two patients and hemophagocytic syndrome in one patient, successfully treated with corticosteroids. Hemorrhagic cystitis associated with Adeno Virus occurred in one patient, leading to irreversible vesicoureteral reflux requiring urinary catheter. Cardiopulmonary arrest due to severe cardiomyopathy occurred in two patients. One patient could be rescued after intensive care including percutaneous cardiopulmonary support and intra-aortic balloon pumping, but another one couldn’t.

Conclusion: Although HSCT brings the favorable results to some patients with severe SSc, we should carefully consider the selection of the patients for HSCT as the treatment of SSc.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/long-term-follow-up-report-on-japanese-patients-with-severe-systemic-sclerosis-after-autologous-hematopoietic-stem-cell-transplantation/