Hematopoietic stem cell transplantation for systemic sclerosis: Brazilian experience

Abstract

Background In the past 20 years, hematopoietic stem cell transplantation (HSCT) has been investigated as treatment for systemic sclerosis (SSc). The goal of HSCT is to eradicate the autoreactive immune system, which is replaced by a new immune repertoire with long-lasting regulation and tolerance to autoantigens. Here, we describe the clinical outcomes of severe and refractory SSc patients that underwent HSCT at a single Brazilian center. Patients and methods This is a longitudinal and retrospective study, including 70 adult SSc patients, with an established diagnosis of SSc, and who underwent autologous HSCT from 2009 to 2016. The procedure included harvesting and cryopreservation of autologous hematopoietic progenitor cells, followed by administration of an immunoablative regimen and subsequent infusion of the previously collected cells. Patients were evaluated immediately before transplantation, at 6 months and then yearly until at least 5-years of post-transplantation follow-up. At each evaluation time point, patients underwent clinical examination, including modified Rodnan’s skin score (mRSS) assessment, echocardiography, high-resolution computed tomography of the lungs and pulmonary function. Results Median (range) age was 35.9 (19–59), with 57 (81.4%) female and median (range) non-Raynaud’s disease duration of 2 (1–7) years. Before transplantation, 96% of the patients had diffuse skin involvement, 84.2%, interstitial lung disease and 67%, positive anti-topoisomerase I antibodies. Skin involvement significantly improved, with a decline in mRSS at all post-transplantation time points until at least 5-years of follow-up. When patients with pre-HSCT interstitial lung disease were analyzed, there was an improvement in pulmonary function (forced vital capacity and diffusing capacity of lung for carbon monoxide) over the 5-year follow-up. Overall survival was 81% and progression-free survival was 70.5% at 8-years after HSCT. Three patients died due to transplant-related toxicity, 9 patients died over follow-up due to disease reactivation and one patient died due to thrombotic thrombocytopenic purpura. Conclusions Autologous hematopoietic progenitor cell transplantation improves skin and interstitial lung involvement. These results are in line with the international experience and support HSCT as a viable therapeutic alternative for patients with severe and progressive systemic sclerosis.

Perspective on Stem Cell Therapy in Organ Fibrosis: Animal Models and Human Studies

“…The most clinically detectable outcome of HSC administration at 5 years post transplantation was improved skin thickness, assessed by modified Rodnan's skin score (mRSS). Of note, enhanced pulmonary function (forced vital capacity and diffusing capacity of carbon monoxide) was also observed [251]. These data are consistent with previous results from three randomized controlled trials that demonstrated the superiority of autologous HSC transplantation over the standard cyclophosphamide treatment: American Scleroderma Stem Cell versus Immune Suppression Trial (ASSIST, phase II) [252], Autologous Stem Cell Transplantation International Scleroderma Trial (ASTIS, phase III) [253], and Scleroderma: Cyclophosphamide or Transplantation (SCOT, phase II) [254].…”

“…Several clinical studies demonstrated the possible benefits of HSC and MSC (mostly SVF/ASC) therapy in SS patients (Table 1). In a recent paper, Henrique-Neto et al [251] reported the results of a longitudinal study that included 70 adult SS patients with a severe SS profile who received autologous HSCs at a mean dose of 5.63 (3.21) × 10 6 CD34 + cells/kg body weight. The most clinically detectable outcome of HSC administration at 5 years post transplantation was improved skin thickness, assessed by modified Rodnan's skin score (mRSS).…”

Life after Autologous Hematopoietic Stem Cell Transplantation for Systemic Sclerosis

“…Disease progression rates varied from 11.9% at 2 years to 30.4% at 4.4 years after ASHCT. 30,31 For studies with longer follow-up, the 8-year progression rate ranged from 10.5% to 24%, 29,37 reaching 42% at 11 years. 34 These different rates are probably secondary to differences in patient selection, different criteria for progression and duration of follow-up.…”

“…16,18,30 Collectively, phase I/II studies show improvement of mRSS early after AHSCT, usually more pronounced within the first year after transplantation, and tending to stabilize thereafter. 16,30,32,37 Longer follow-up studies show sustained mRSS improvement for at least 60 and 96 months, respectively. 29,37 In a post-hoc analysis of a phase I/II non-randomized study, patients who underwent AHSCT with and without graft selection were compared.…”

“…16,30,32,37 Longer follow-up studies show sustained mRSS improvement for at least 60 and 96 months, respectively. 29,37 In a post-hoc analysis of a phase I/II non-randomized study, patients who underwent AHSCT with and without graft selection were compared. CD34+ graft selection had an overall positive influence on patient outcomes but was specifically associated with improvements in mRSS.…”