Long-Term Safety and Efficacy of Autologous Hematopoietic Cell Transplantation for Patients with Progressive Systemic Sclerosis

Autologous hematopoietic cell transplantation (HCT) has been introduced in patients with progressive systemic sclerosis, given the dismal prognosis with conventional therapy. We aimed to assess the long-term efficacy and safety of HCT modality for severe and progressive systemic sclerosis refractory to conventional therapy.

We retrospectively studied all consecutive adult patients, with an established diagnosis of progressive systemic sclerosis refractory to conventional therapy, who were referred to our JACIE-accredited Unit from 2005 to 2024. Peripheral blood stem cells (PBSCs) were collected using cyclophosphamide (4gr/m²) and GCSF. An immunoablative conditioning regimen of cyclophosphamide (200 mg/kg) and anti-thymocyte globulin (ATG; 7.5 mg/kg) was administered. Disease assessments were done before and after mobilization treatment and post-transplant, focusing on skin sclerosis and ulcers, pulmonary function, cardiac involvement, gastrointestinal manifestations, the necessity for additional immunosuppressive therapy and their overall well - being. The evaluation at each time included clinical examination, assessment of modified Rodnan's skin score (mRSS), diffusing capacity of lung for carbon monoxide (DLCO), forced expiratory volume in the first second (FEV1) for pulmonary function, cardiology assessment including MRI and questionnaires regarding daily functional ability and quality of life.

A total of 17 patients underwent HCT, 14 females (82%) and 3 males (18%). Median age was 34 (range 21-50) with median disease onset 3 (2-13) years. Before transplantation, 13/17 (76%) of the patients had diffuse skin involvement with a mean mRSS of 31 (2-49), 2/17 (12%) pulmonary hypertension and 13/17 (76%) visceral involvement. Skin sclerosis improvement was significant, depicted via mRSS mean overall reduction of 77%, lung function assessed by DLCO and FEV1, remained stable in 8/15 (53%), improved in 5/15 (33%) and deteriorated in 2/15 (13%). Gastrointestinal manifestations were improved in 12/14 (86%) while all patients (16/16) reported a great impact on their quality of life. 10/16 (63%) of the patients were free of immunosuppressive drugs after the HCT. Overall survival was 16/17 (94.2%). Concerning TRM, there was 1 death early post-transplant in a heavily pre-treated patient with severe pulmonary disease. The patient died due to sepsis and multiorgan failure in ICU.

In conclusion, autologous HCT with an immunoablative regimen with cyclophosphamide and ATG improves skin and gastrointestinal manifestations, stabilises lung function and alters the quality of patients' life radically. These results are in line with international experience and support HCT as a viable therapeutic alternative. In the era of novel cellular therapies in autoimmune diseases, personalized selection of patients is warranted.

Gavriilaki:AstraZeneca Pharmaceuticals: Honoraria; Omeros Pharmaceuticals: Honoraria; Sanofi Pharmaceuticals: Honoraria; Sobi Pharmaceuticals: Honoraria; Jazz Pharmaceuticals: Research Funding. Yannaki:bluebird bio, Inc.: Research Funding.