Efficacy and safety of autologous haematopoietic stem cell transplantation in systemic sclerosis: a systematic review of the literature

Abstract

We aimed to assess the efficacy of autologous haematopoietic stem cell transplantation (HSCT) for skin sclerosis (SSc) and lung function in SSc. We performed a systematic literature review in the PubMed and Scopus databases from the earliest records to March 2016. We assessed study quality using the Cochrane tool for randomized studies, the Newcastle-Ottawa Scale for controlled cohort studies and an 18-item quality-appraisal checklist for case series. The primary outcome was the improvement of skin thickening using the modified Rodnan Skin Score (mRSS). The secondary outcome was efficacy on lung function, using diffusing capacity of the lungs for carbon monoxide and forced vital capacity (FVC). The safety of the procedure was evaluated. The literature search identified 431 citations. There were 38 studies involving a total of 344 patients who fulfilled our inclusion criteria. No meta-analysis was performed due to a high heterogeneity. There was a significant improvement in mRSS in the majority of the reports (P < 0·05), and the results were sustained for up to 8 years after autologous HSCT. The randomized studies and the four cohort studies each showed a slight but statistically significant improvement in FVC at 1 or 2 years. The treatment-related mortality calculated by pooling patients of 35 studies (336 patients with a follow-up up to 146 months) was 8·3% after autologous HSCT and 1% in cyclophosphamide-treated groups. Despite heterogeneity among the studies, we determined that autologous HSCT significantly improved cutaneous fibrosis and slightly improved FVC. Safety of autologous HSCT is acceptable given the severity of the disease. This systematic review was registered on PROSPERO, number CRD42016027951.

Autologous Hematopoietic Stem Cell Transplantation for Treatment of Systemic Sclerosis

“…All the patients in the AHSCT arm experienced a significant improvement in the mRSS and functional capacity (HAQ, Disability Index). These results are consistent with previous observations from observational, pilot studies and registries that showed a marked impact of AHSCT on skin thickness ( 1 ). At the moment, no other studies on therapeutic intervention in diffuse scleroderma have shown to be so effective in stopping and reversing scleroderma skin involvement.…”

“…Several case reports and different phase I-II studies formed the basis for randomized controlled studies (RCTs) with AHSCT in SSc ( 1 – 4 ). All the RCTs have similar eligibility criteria and control treatment but exact comparability of cohorts, procedures and outcomes is questionable (see Tables 2 , 3 ).…”

“…Hematopoietic stem cell transplantation, commonly used to treat hematological malignancies, has evolved in the last 20 years as a specific therapy for severe and therapy-refractory autoimmune diseases. Since the first case series, and following prospective and retrospective studies [recently reviewed by Eyraud et al ( 1 )] reporting the feasibility and efficacy of AHSCT in SSc on skin thickening and stabilization of internal organ function, randomized controlled trials have recently provided evidence that AHSCT is a real disease-modifying treatment for diffuse SSc inducing better long-term survival in comparison with intravenous cyclophosphamide ( 2 – 4 ). These data have provided convincing proof of the superiority of AHSCT over conventional therapies even considering the intrinsic risk of the procedure.…”

A randomised, open-label trial to assess the optimal treatment strategy in early diffuse cutaneous systemic sclerosis: the UPSIDE study protocol

“…[7][8][9] In addition, three systematic reviews were published on the efficacy and safety of HSCT in SSc. [10][11][12] In all reviews, it was concluded that HSCT provided a survival benefit, improved skin involvement and stabilised pulmonary function compared with intravenous CYC for 12 months. Heterogeneity between studies, however, prevented meta-analysis, yet a trend towards better outcome was observed in patients with a shorter disease duration before HSCT.…”

Avaliação do impacto do transplante autólogo de células-tronco hematopoiéticas sobre a vasculopatia em pacientes com esclerose sistêmica

“…Os principais ensaios clínicos fase 2 e 3 (ASSIST, ASTIS e SCOT), compararam o TCTH com terapia convencional com doses endovenosas de ciclofosfamida. Os resultados destes estudos indicaram uma superioridade do tratamento com transplante, sumarizados através de uma metanálise de 2018, na qual se conclui que houve melhora nos níveis de CVF após 1 a 2 anos do tratamento (EYRAUD et al, 2018).…”