van Besien Koen, Hari Parameswaran, Zhang Mei-Jie, Liu Hong-Tao, Stock Wendy, Godley Lucy, Odenike Olatoyosi, Larson Richard, Bishop Michael, Wickrema Amittha, Gergis Usama, Mayer Sebastian, Shore Tsiporah, Tsai Stephanie, Rhodes Joanna, Cushing Melissa M, Korman Sandra, Artz Andrew
Department of Hematology/Oncology and Meyer Cancer Center - Stem Cell Transplant Program, Weill Cornell Medical College, New York, NY, USA
Center for International Bone Marrow Transplant Research, Medical College of Wisconsin, Milwaukee, WI, USA.
Haematologica. 2016 May;101(5):634-43. doi: 10.3324/haematol.2015.138594. Epub 2016 Feb 11.
Umbilical cord blood stem cell transplants are commonly used in adults lacking HLA-identical donors. Delays in hematopoietic recovery contribute to mortality and morbidity. To hasten recovery, we used co-infusion of progenitor cells from a partially matched related donor and from an umbilical cord blood graft (haplo-cord transplant). Here we compared the outcomes of haplo-cord and double-cord transplants. A total of 97 adults underwent reduced intensity conditioning followed by haplo-cord transplant and 193 patients received reduced intensity conditioning followed by double umbilical cord blood transplantation. Patients in the haplo-cord group were more often from minority groups and had more advanced malignancy. Haplo-cord recipients received fludarabine-melphalan-anti-thymocyte globulin. Double umbilical cord blood recipients received fludarabine-cyclophosphamide and low-dose total body irradiation. In a multivariate analysis, haplo-cord had faster neutrophil (HR=1.42, P=0.007) and platelet (HR=2.54, P<0.0001) recovery, lower risk of grade II-IV acute graft-versus-host disease (HR=0.26, P<0.0001) and chronic graft-versus-host disease (HR=0.06, P<0.0001). Haplo-cord was associated with decreased risk of relapse (HR 0.48, P=0.001). Graft-versus-host disease-free, relapse-free survival was superior with haplo-cord (HR 0.63, P=0.002) but not overall survival (HR=0.97, P=0.85). Haplo-cord transplantation using fludarabine-melphalan-thymoglobulin conditioning hastens hematopoietic recovery with a lower risk of relapse relative to double umbilical cord blood transplantation using the commonly used fludarabine-cyclophosphamide-low-dose total body irradiation conditioning. Graft-versus-host disease-free and relapse-free survival is significantly improved. Haplo-cord is a readily available graft source that improves outcomes and access to transplant for those lacking HLA-matched donors. Trials registered at clinicaltrials.gov identifiers 00943800 and 01810588.
脐带血干细胞移植常用于缺乏 HLA 相匹配供体的成年人。造血恢复延迟会导致死亡率和发病率升高。为了加速恢复，我们采用了将来自部分匹配的相关供体的祖细胞与脐带血移植物共同输注的方法（单倍体-脐带移植）。在此，我们比较了单倍体-脐带移植和双脐带移植的结果。共有 97 名成年人接受了减低强度预处理，随后进行单倍体-脐带移植，193 名患者接受了减低强度预处理，随后进行双脐带血移植。单倍体-脐带组的患者更多来自少数群体，且恶性肿瘤病情更严重。单倍体-脐带移植受者接受氟达拉滨-马法兰-抗胸腺细胞球蛋白治疗。双脐带血移植受者接受氟达拉滨-环磷酰胺和低剂量全身照射。在多变量分析中，单倍体-脐带移植的中性粒细胞（风险比[HR]=1.42，P=0.007）和血小板（HR=2.54，P<0.0001）恢复更快，II-IV 级急性移植物抗宿主病（HR=0.26，P<0.0001）和慢性移植物抗宿主病（HR=0.06，P<0.0001）的风险更低。单倍体-脐带移植与复发风险降低相关（HR 0.48，P=0.001）。无移植物抗宿主病、无复发生存率单倍体-脐带移植更佳（HR 0.63，P=0.002），但总生存率无差异（HR=0.97，P=0.85）。与使用常用的氟达拉滨-环磷酰胺-低剂量全身照射预处理的双脐带血移植相比，采用氟达拉滨-马法兰-抗胸腺细胞球蛋白预处理的单倍体-脐带移植能加速造血恢复，且复发风险更低。无移植物抗宿主病和无复发生存率显著提高。单倍体-脐带是一种易于获得的移植物来源，可改善缺乏 HLA 匹配供体者的移植结局并增加移植机会。试验在 clinicaltrials.gov 上注册，标识符分别为 00943800 和 01810588。
