A small cohort of eight adolescents and young adults with treatment-refractory juvenile-onset systemic sclerosis (JSSc) has shown that autologous stem cell transplantation (ASCT) is a viable treatment option in young people.

The prospective US study, published in Annals of the Rheumatic Diseases [link here], found durable multi-system improvement including an event-free survival of 100% at a median follow-up of 30 months.

All patients were able to discontinue immunosuppression from ASCT with only one reinitiating after disease flare at 20 months.

“Our findings suggested that for patients who fail multiple DMARDs, including MMF, rituximab, and tocilizumab, ASCT remains a viable and potentially transformative option,” it said.

“These data also raise the possibility that earlier consideration of ASCT in carefully selected high-risk patients, particularly those demonstrating early nonresponse to initial therapy, may improve long-term outcomes.”

The patients, aged from 14 to 21 years at the time of ASCT, had moderate-to-severe disease defined as severe state or progression of ILD, skin thickening, or musculoskeletal involvement, and were refractory to at least 2 DMARDs. The median duration of disease from onset to ASCT was 5.5 years.

Regarding the primary outcome of safety, the study found post-transplant complications were limited to viral infections including COVID-19. No patients had scleroderma renal crisis or developed new JSSc manifestations.

Event-free survival, defined as the absence of death, respiratory failure, renal failure, or cardiomyopathy, was achieved by all patients.

In secondary endpoints:

• All patients showed skin improvement with median mRSS score declining from 24 to 5 at 6 months and to 2 at 12 months.
• Patients transplanted for pulmonary indications had an initial decline in FVC or DLCO followed by stabilisation.
• Both patients with pulmonary hypertension (pHTN) showed normalised pulmonary pressures.
• No patients demonstrated cardiac worsening or progression.
• No patients experienced renal involvement.
• All patients reported clinically meaningful improvement in quality of life in the first six months after ASCT, and functional recovery “…with meaningful life changes such as return to school, employment, travel, and family planning.”
• Musculoskeletal outcomes including finger-to-palm flexion distance, oral aperture and joint contractures improved across the cohort.
• GI symptom outcomes using the Gastrointestinal Tract (GIT) score improved in most patients.
• Raynaud’s phenomenon and digital vasculopathy symptoms improved.

“In our cohort of 8 paediatric and young adult patients, ASCT using a reduced-dose total body irradiation regimen was safe, feasible, and associated with clinically meaningful multisystem improvement as early as 3 months, sustained for up to 4 years posttransplant,” the study said.

The investigators, from the University of Pittsburgh Medical Center, said the findings were consistent with those seen in adults with SSc undergoing ASCT.

“Despite severe, heterogeneous disease and prolonged disease courses, ASCT was safe and resulted in durable clinical responses, suggesting that disease duration, subtype, and severity should not be absolute contraindications to ASCT consideration in JSSc.”

“Importantly, although pHTN has historically been an exclusion criterion in adult ASCT trials due to cardiac risk, both patients with pHTN in our cohort tolerated ASCT well and demonstrated improvement in pulmonary artery pressures, allowing de-escalation of vasodilator therapy.”

They said despite modified radiation, ongoing surveillance would be necessary for potential late effects such as endocrine dysfunction, growth impairment, cataracts, and secondary malignancies.