Georges George E, Khanna Dinesh, Wener Mark H, Mei Matthew G, Mayes Maureen D, Simms Robert W, Sanchorawala Vaishali, Hosing Chitra, Kafaja Suzanne, Pawarode Attaphol, Holmberg Leona A, Kolfenbach Jason, Furst Daniel E, Sullivan Keith M, Huang Suiyuan, Gooley Ted, Nash Richard A
Northwestern University Feinberg School of Medicine, Chicago, Fred Hutchinson Cancer Center and University of Washington, Seattle.
University of Michigan, Ann Arbor.
Arthritis Rheumatol. 2025 May;77(5):571-581. doi: 10.1002/art.43072. Epub 2025 Jan 14.
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.
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.
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.
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.
两项针对弥漫性系统性硬化症（SSc）患者的随机试验表明，与每月使用环磷酰胺（CY）相比，采用CD34+选择的外周血干细胞（PBSC）进行自体造血干细胞移植（AHSCT）可带来总生存期（OS）和无事件生存期（EFS）优势。我们探讨了AHSCT后采用未修饰的PBSC移植物并继以霉酚酸酯（MMF）维持治疗，而非采用CD34+选择的移植物，是否能带来相似的AHSCT疗效。
20例高危SSc患者入组一项前瞻性单臂试验，接受200 mg/kg CY和马抗胸腺细胞球蛋白（ATG；CY200/ATG）治疗，随后接受未处理的自体PBSC，然后在AHSCT后2个月开始MMF维持治疗。
AHSCT后5年的OS和EFS点估计值分别为85%（95%置信区间[CI] 60.4%-94.9%）和75%（95% CI 50%-88.7%）。存活患者移植后的中位随访时间为7.5年（范围5.6-11.6年）。8例患者（40%）在移植后早期需要重症监护病房治疗。2例患者（10%）发生早期移植相关死亡。5例患者在AHSCT后出现SSc复发/进展。9例抗RNA聚合酶III抗体阳性患者中有4例既往有硬皮病肾危象且研究入组时估计肾小球滤过率（eGFR）处于最低四分位数；所有4例患者在移植后早期均出现长期器官衰竭/死亡。
我们观察到，对于SSc患者，采用CY200/ATG、未处理的PBSC以及移植后MMF维持治疗进行AHSCT后，OS和EFS情况良好，这与采用CD34+移植物选择的试验结果相当。我们确定了一个可能的危险因素，即移植前eGFR低，与AHSCT后的不良结局相关。
