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Machine learning predicts stem cell transplant response in severe scleroderma.

Jennifer M Franks1,2, Viktor Martyanov1,2, Yue Wang1,2

  • 1Molecular and Systems Biology, Dartmouth College Geisel School of Medicine, Hanover, New Hampshire, USA.

Annals of the Rheumatic Diseases
|September 16, 2020
PubMed
Summary
This summary is machine-generated.

Patients with the fibroproliferative subtype of scleroderma (SSc) significantly benefit from hematopoietic stem cell transplant (HSCT) over cyclophosphamide (CYC). This finding suggests subset stratification can guide SSc treatment decisions for HSCT.

Keywords:
cyclophosphamidesystemic sclerosistreatment

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Area of Science:

  • Immunology
  • Genomics
  • Rheumatology

Background:

  • The Scleroderma: Cyclophosphamide or Transplantation (SCOT) trial showed hematopoietic stem cell transplant (HSCT) offers clinical benefits over cyclophosphamide (CYC) for scleroderma.
  • Peripheral blood cell (PBC) samples from the SCOT trial were analyzed to explore treatment response predictors.

Purpose of the Study:

  • To determine if intrinsic gene expression subsets of scleroderma predict long-term response to HSCT versus CYC.
  • To identify differential gene expression patterns associated with treatment response in scleroderma patients.

Main Methods:

  • Gene expression analysis of PBCs from 63 SCOT trial participants at baseline and follow-up.
  • Stratification of participants by intrinsic gene expression subsets and evaluation of event-free survival (EFS).
  • Analysis of differentially expressed genes (DEGs) between treatment arms and subsets.

Main Results:

  • Participants in the fibroproliferative subset showed significantly improved EFS with HSCT compared to CYC (p=0.0091).
  • No significant EFS difference was observed between HSCT and CYC for normal-like (p=0.77) or inflammatory (p=0.1) subsets.
  • HSCT arm exhibited more DEGs and significant immune pathway alterations compared to the CYC arm.

Conclusions:

  • The fibroproliferative subset of scleroderma patients derives the most substantial long-term benefit from HSCT.
  • Intrinsic subset stratification may identify scleroderma patients who will significantly benefit from HSCT, optimizing treatment selection.