{
  "abstract": "Introduction Diffuse cutaneous systemic sclerosis (dcSSc) carries high morbidity and mortality. Several treatments aim to modify disease course, including immunosuppressants and autologous hematopoietic stem cell transplantation (HSCT). The optimal timing of HSCT remains unclear, particularly whether it should be used upfront or reserved for patients refractory to immunosuppressive therapy. This open-label randomized trial compares two strategies for early dcSSc: (A) upfront HSCT versus (B) conventional immunosuppressants, with rescue HSCT for treatment failure. Here, we present preliminary interim data on enrolment and safety.Material and Methods Patients with early progressive dcSSc with poor prognosis were recruited from seven sites across three European countries. Patients with extensive organ damage or prior cyclophosphamide (CYC) or DMARD use >12 months were excluded. Arm A (upfront HSCT) included mobilization with CYC, CD34+ selection, and conditioning with ATG and CYC. Arm B received 12 monthly CYC pulses (750 mg/m 2) followed by at least one year of mycophenolate mofetil. Criteria for rescue HSCT or DMARD use post-HSCT were predefined and reviewed by the study team. Patients will be followed for 5 years and the primary outcome is the global rank composite score taking into account death, event-free survival, forced vital capacity, Health Assessment Questionnaire - Disability Index, and Modified Rodnan Skin Score (mRSS), at 2 years after randomisation.Results From October 2020 to October 2025, 52 patients were randomized (26 per study arm; recruitment target is 60). Mean age was 48.6 years (SD 10.6), 46% was female, mean disease duration 11.4 months (SD 7), mean mRSS 23.6 (SD 8.1) and interstitial lung disease present in 62% ( table 1). During follow-up 11 (42%) patients in arm B required rescue HSCT, while 3 (12%) needed DMARDs post-HSCT.There were 23 severe adverse events (SAE) in arm A and 12 in arm B, of which respectively 30% and 33% were definitely treatment-related. The most frequent SAEs was infection with 39% vs 8% cases. The infections were viral (37.5%), bacterial (25%), and fungal (37.5%). Two deaths occurred in arm A, one due to disease progression and one related to cytokine release syndrome. In arm B, one patient died due to disease progression. Treatment related mortality (TRM) in arm A was 4% (N=1), TRM in the HSCT treated patients including rescue HSCTs (N=37) was 3% (N=1).Conclusions Early intensive treatment in high-risk dcSSc appears feasible and safe. In fact, the markedly lower HSCT-related mortality compared to previous trials might suggest that earlier intervention improves safety while maintaining efficacy.Abstract OC.54 Table 1Baseline characteristics",
  "authors": [
    {
      "affiliations": [
        "University Medical Centre Utrecht, Department of Rheumatology & Clinical Immunology, Utrecht, The Netherlands"
      ],
      "name": "Julia Spierings"
    },
    {
      "affiliations": [
        "University Medical Centre Utrecht, Department of Hematology, Utrecht, The Netherlands"
      ],
      "name": "Anna Van Rhenen"
    },
    {
      "affiliations": [
        "Sheffield Teaching Hospitals NHS Foundation Trust, Department of Rheumatology, Sheffield, UK"
      ],
      "name": "Mohammed Akil"
    },
    {
      "affiliations": [
        "IRCCS Ospedale San Raffaele s.r.l, Unit of Hematology and Bone Marrow Transplantation, MIlan, Italy"
      ],
      "name": "Fabio Ciceri"
    },
    {
      "affiliations": [
        "ASST G. Pini-CTO, Scleroderma Clinic, Rheumatology Department, Milan, Italy"
      ],
      "name": "Nicoletta Del Papa"
    },
    {
      "affiliations": [
        "Amsterdam University Medical Centre, Department of Hematology, Amsterdam, The Netherlands"
      ],
      "name": "Arjan A van de Loosdrecht"
    },
    {
      "affiliations": [
        "University Medical Centre Utrecht, Department of Rheumatology & Clinical Immunology, Utrecht, The Netherlands"
      ],
      "name": "Anne Karien CA Marijnissen"
    },
    {
      "affiliations": [
        "Leiden University Medical Center, Department of Hematology, Leiden, The Netherlands"
      ],
      "name": "Erik WAF Marijt"
    },
    {
      "affiliations": [
        "Radboud University Medical Center, Department of Hematology, Nijmegen, The Netherlands"
      ],
      "name": "Mieke WH Roeven"
    },
    {
      "affiliations": [
        "Sheffield Teaching Hospitals NHS Foundation Trust, Department of Hematology, Sheffield, UK"
      ],
      "name": "John Snowden"
    },
    {
      "affiliations": [
        "Radboud University Medical Center, Department of Rheumatology, Nijmegen, The Netherlands"
      ],
      "name": "Madelon C Vonk"
    },
    {
      "affiliations": [
        "Amsterdam University Medical Centre, Department of Rheumatology, Amsterdam, The Netherlands"
      ],
      "name": "Alexandre E Voskuyl"
    },
    {
      "affiliations": [
        "Leiden University Medical Center, Department of Rheumatology, Leiden, The Netherlands"
      ],
      "name": "Jeska K de Vries-Bouwstra"
    },
    {
      "affiliations": [
        "University Medical Centre Utrecht, Department of Rheumatology & Clinical Immunology, Utrecht, The Netherlands"
      ],
      "name": "Paco MJ Welsing"
    },
    {
      "affiliations": [
        "University Medical Centre Utrecht, Department of Rheumatology & Clinical Immunology, Utrecht, The Netherlands"
      ],
      "name": "Jacob M van Laar"
    }
  ],
  "title": "OC.54 Timing matters: early autologous stem cel transplantation shows a lower mortality in high-risk diffuse cutaneous systemic sclerosis – preliminary results from the upside trial",
  "uid": "18e32468-fda2-5825-ba43-157fa4f83bd6"
}