Autologous Nonmyeloablative Hematopoietic Stem Cell Transplantation for Diffuse Cutaneous Systemic Sclerosis: Identifying Disease Risk Factors for Toxicity and Long‐Term Outcomes in a Prospective, Single‐Arm Trial
Year: 2024
Type: article
Study design: Clinical Trial
Abstract: OBJECTIVE: Two randomized trials for patients with diffuse systemic sclerosis (SSc) demonstrated an overall survival (OS) and event-free survival (EFS) advantage of autologous hematopoietic stem cell transplantation (AHSCT) using CD34+ selected peripheral blood stem cells (PBSCs) compared with monthly cyclophosphamide (CY). We asked if an unmodified PBSC graft followed by maintenance mycophenolate mofetil (MMF) after AHSCT, instead of a CD34+ selected graft, could provide comparable AHSCT outcomes. METHODS: Twenty patients with high-risk SSc were enrolled in a prospective, single-arm trial with CY 200 mg/kg and horse antithymocyte globulin (ATG; CY200/ATG), followed by unmanipulated autologous PBSC, and then MMF maintenance starting at 2 months after AHSCT. RESULTS: Point estimates of OS and EFS at 5 years after AHSCT were 85% (95% confidence interval [CI] 60.4%-94.9%) and 75% (95% CI 50%-88.7%), respectively. Median follow-up was 7.5 years (range 5.6-11.6) after transplant for living patients. Eight patients (40%) required intensive care unit treatment early after transplant. Early transplant-related mortality occurred in two patients (10%). Five patients developed relapse/progression of SSc after AHSCT. Four of nine patients with anti-RNA polymerase III antibodies had prior scleroderma renal crisis and the lowest quartile of estimated glomerular filtration rate (eGFR) on study entry; all four patients developed prolonged organ failure/death early after transplant. CONCLUSION: We observed favorable OS and EFS after AHSCT for patients with SSc, using CY200/ATG, unmanipulated PBSCs, and MMF posttransplant maintenance, which was comparable to trials with CD34+ graft selection. We identified a possible risk factor, pretransplant low eGFR, for adverse outcomes after AHSCT.
Source: Arthritis & Rheumatology
DOI: 10.1002/art.43072
Institutions: Northwestern University, University of Washington, Fred Hutch Cancer Center, University of Michigan, Michigan Medicine, City Of Hope National Medical Center, The University of Texas Health Science Center at Houston, Dartmouth College, Boston University, Boston Medical Center, The University of Texas MD Anderson Cancer Center, University of California, Los Angeles, University of Colorado Anschutz, Duke University, Duke Medical Center, Colorado Blood Cancer Institute
Language: English
Subfield: Pathology and Forensic Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $4,940
OpenAlex ID: W4404975323