School of Medicine in Katowice, Department of Hematology and Bone Marrow Transplantation, Medical University of Silesia, Dąbrowski street 25, 40-032, Katowice, Poland.
School of Medicine in Katowice, Department of Rheumatology, Medical University of Silesia, Katowice, Poland.
Clin Rheumatol. 2018 Jun;37(6):1709-1714. doi: 10.1007/s10067-017-3954-5. Epub 2017 Dec 18.
Autologous hematopoietic stem cell transplantation (AHSCT) is thought to be effective therapeutic approach in patients with poor prognosis systemic sclerosis; however, the toxicity remains a challenge. Between years 2003 and 2016, we enrolled 18 patients with systemic sclerosis at median age at transplant of 52 years (range 24-68). The median duration of disease before AHSCT was 14 months (range 2-85). Peripheral blood stem cells were mobilized with cyclophosphamide (CY) and granulocyte colony-stimulating factor. Conditioning regimen included CY (200 mg/kg) and alemtuzumab (median dose, 60 mg) [n = 11], melphalan (MEL; 140 mg/m2) and alemtuzumab [n = 2], CY and rabbit anti-thymocyte globulin (rATG; 7.5 mg/kg) [n = 4], and CY alone (n = 1). Four deaths occurred early after transplant. There were three males and one female at median age at death of 51 years (range 24-68). The AHSCT-related deaths have been observed on days + 1, + 4, + 9, and + 15 after procedure. The causes of death included bilateral pneumonia followed by multi-organ failure in three patients and myocardial infarction in one. Three patients expired late during post-transplant follow-up, after 5, 21, and 42 months. The causes of death were disease progression in two patients and sudden heart attack in one. Eleven patients are alive after median follow-up after AHSCT of 42.0 months (range 0-95). Before proceeding to AHSCT in systemic sclerosis, there is a strong need to optimize patient selection to reduce toxicity. The administration of alemtuzumab should be avoided due to high risk of life-threatening infectious complications.
自体造血干细胞移植(AHSCT)被认为是预后不良的系统性硬化症患者的有效治疗方法;然而,毒性仍然是一个挑战。在 2003 年至 2016 年间,我们共纳入 18 例系统性硬化症患者,移植时的中位年龄为 52 岁(范围 24-68 岁)。AHSCT 前疾病的中位持续时间为 14 个月(范围 2-85 个月)。外周血造血干细胞采用环磷酰胺(CY)和粒细胞集落刺激因子动员。预处理方案包括 CY(200mg/kg)和阿仑单抗(中位剂量 60mg)[n=11]、马法兰(MEL;140mg/m2)和阿仑单抗[n=2]、CY 和兔抗胸腺细胞球蛋白(rATG;7.5mg/kg)[n=4]以及单独使用 CY[n=1]。4 例患者在移植后早期死亡。死亡患者的中位年龄为 51 岁(范围 24-68 岁),其中男性 3 例,女性 1 例。AHSCT 相关死亡发生在移植后第 1、4、9 和 15 天。死亡原因包括 3 例患者的双侧肺炎继发多器官功能衰竭和 1 例患者的心肌梗死。3 例患者在移植后随访期间死亡,中位时间分别为 5、21 和 42 个月。死亡原因分别为 2 例患者疾病进展和 1 例患者突发心脏病。11 例患者在 AHSCT 后中位随访 42.0 个月(范围 0-95)后仍存活。在进行系统性硬化症的 AHSCT 之前,强烈需要优化患者选择以降低毒性。由于存在危及生命的感染并发症的高风险,应避免使用阿仑单抗。