Allogeneic Blood and Marrow Transplantation Program, Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, Toronto, Canada.
Allogeneic Blood and Marrow Transplantation Program, Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, Toronto, Canada.
Biol Blood Marrow Transplant. 2018 Nov;24(11):2259-2264. doi: 10.1016/j.bbmt.2018.07.008. Epub 2018 Aug 7.
Haploidentical hematopoietic stem cell transplantation (haploHSCT) with conditioning regimens using post-transplant cyclophosphamide (PTCy) for peripheral blood stem cell (PBSC) grafts is limited by comparably higher rates of acute and chronic graft-versus-host disease (GVHD). Antithymocyte globulin (ATG) may mitigate this risk. We evaluated haploHSCT after reduced-intensity conditioning (RIC) with ATG, PTCy, and cyclosporine to prevent rejection and GVHD. Fifty adults underwent haploHSCT from August 2016 to February 2018. RIC included fludarabine (30 mg/m/day on days -5 to -2), busulfan (3.2 mg/m/day on days -3 and -2), and total body irradiation (200 cGy) on day -1. Unmanipulated PBSCs were infused on day 0. GVHD prophylaxis included ATG (4.5 mg/kg over days -3 to -1), PTCy (50 mg/kg/day on days +3 and +4), and cyclosporine from day +5. Median age was 56 years (range, 22 to 70 years); 25 (73.5%) patients were in first complete remission (CR1), 5 (14.7%) were in second complete remission (CR2), and 8 (23.5%) had active disease. Median time to neutrophil engraftment was 16 days (range, 8 to 43 days). At day +100, the cumulative incidence of acute GVHD of any grade, and grades III to IV was 38.3% and 5.2%, respectively. Mild chronic GVHD was seen in 15.5%. Cytomegalovirus (CMV) reactivation occurred in 37 (74%) cases and CMV disease occurred in 4 (11.5%) cases. Epstein-Barr virus (EBV) reactivation occurred in 21 (61.8%) patients. The incidence of histologically confirmed post-transplantation lymphoproliferative disorder (PTLD) was 5.8%. Four patients received rituximab. There were no CMV, EBV, or PTLD-related deaths. Six-month and 1-year overall survival (OS), cumulative incidence of relapse (CIR), and nonrelapse mortality (NRM) were 73.9%, 10.2%, and 19.4%, respectively, and 48.1%, 16% and 38.2%, respectively. Infection was the most common cause of death (18%). Unmanipulated haploidentical PBSC transplantation following RIC with ATG, PTCy, and cyclosporine as a GVHD prevention strategy results in low rates of acute and chronic GVHD.
单倍体造血干细胞移植(haploHSCT)联合外周血干细胞(PBSC)移植后环磷酰胺(PTCy)预处理方案用于治疗疾病,会导致急性和慢性移植物抗宿主病(GVHD)发生率较高。抗胸腺细胞球蛋白(ATG)可能会降低这种风险。我们评估了使用 ATG、PTCy 和环孢素进行的减低强度预处理(RIC)后行haploHSCT 预防排斥和 GVHD 的效果。
50 例成年人于 2016 年 8 月至 2018 年 2 月接受了单倍体 HSCT。RIC 方案包括氟达拉滨(30mg/m,每天,在-5 至-2 天)、白消安(3.2mg/m,每天,在-3 和-2 天)和全身照射(200cGy,在-1 天)。非清髓性 PBSC 在第 0 天输注。GVHD 预防方案包括 ATG(4.5mg/kg,在-3 至-1 天)、PTCy(50mg/kg,每天,在+3 和+4 天)和环孢素(从+5 天开始)。
中位年龄为 56 岁(范围:22-70 岁);25 例(73.5%)患者处于完全缓解 1 期(CR1),5 例(14.7%)处于完全缓解 2 期(CR2),8 例(23.5%)处于疾病活跃期。中性粒细胞植入的中位时间为 16 天(范围:8-43 天)。在第 100 天,急性 GVHD 的累积发生率为任何级别和 3-4 级分别为 38.3%和 5.2%。轻度慢性 GVHD 为 15.5%。37 例(74%)发生巨细胞病毒(CMV)再激活,4 例(11.5%)发生 CMV 疾病。21 例(61.8%)患者发生 EBV 再激活。组织学证实的移植后淋巴增殖性疾病(PTLD)发生率为 5.8%。4 例患者接受了利妥昔单抗治疗。无 CMV、EBV 或 PTLD 相关死亡。6 个月和 1 年总生存率(OS)、累积复发率(CIR)和非复发死亡率(NRM)分别为 73.9%、10.2%和 19.4%和 48.1%、16%和 38.2%。感染是导致死亡的最常见原因(18%)。
RIC 联合 ATG、PTCy 和环孢素作为 GVHD 预防策略,用于非清髓性单倍体 PBSC 移植,可降低急性和慢性 GVHD 的发生率。