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移植后环磷酰胺治疗导致单倍体造血细胞移植后不良结局的风险因素:来自两中心的分析。

Risk factors for adverse outcomes following haploidentical hematopoietic cell transplantation with posttransplant cyclophosphamide: a two-center analysis.

机构信息

Bone Marrow Transplantation Department, Hospital Israelita Albert Einstein, Guaramomis 480/64, São Paulo, SP, CEP 04076-010, Brazil.

Bone Marrow Transplantation Department, Instituto Nacional de Cancer, Rio de Janeiro, Brazil.

出版信息

Ann Hematol. 2022 Aug;101(8):1795-1802. doi: 10.1007/s00277-022-04865-0. Epub 2022 May 16.

Abstract

Allogeneic hematopoietic cell transplantation (HCT) is a potentially curative therapy for several malignant hematologic diseases and alternative donors, including haploidentical, play a significant role in HCT. Despite the increasing use of haplo-HCT with PTCy, some questions remain open. The objective of the present study was to investigate risk factors for adverse outcomes after haplo-HCT with PTCy. This is a retrospective study conducted at two Brazilian centers. A total of 103 patients with hematologic malignancies who underwent first allogeneic, haploidentical HCT with PTCy were included. Risk factors for death were age at transplant (HR = 1.03 for each year; p = 0.002) and high/very high disease risk index (DRI; HR = 2.77; p = 0.0007) and mother as the donor compared with other donors (HR = 3.53; p = 0.005). In multivariate analysis, PFS was significantly poorer for older patients (HR = 1.02; p = 0.006), high/very high DRI (HR = 2.39; p = 0.003), and mother as the donor compared with other donors (HR = 3.18; p = 0.006). Relapse rate was higher for high/very high DRI (HR = 4.01; p = 0.002) and mother as the donor compared with other donors (HR = 2.52; p = 0.05). NRM was higher for older patients (HR = 1.03 for each year; p = 0.03). Tacrolimus was a protective factor for grades II-IV aGVHD (HR = 0.46; p = 0.04) compared with cyclosporine. Peripheral blood (PBSC) was a risk factor for cGVHD (HR = 3.48; p = 0.006), while tacrolimus was protective (HR = 0.30; p = 0.009). Mother as the donor compared with other donors was also a risk factor for poorer OS, PFS, and relapse, suggesting that this combination should be avoided. Tacrolimus was protective for both grades II-IV aGVHD and cGVHD, suggesting that tacrolimus may be more effective than cyclosporine in preventing GVHD. PBSC was a risk factor for cGVHD without any impact on relapse. Prospective studies comparing tacrolimus with cyclosporine are awaited.

摘要

异基因造血细胞移植(HCT)是多种恶性血液病的潜在治愈疗法,供者包括单倍体相合,在 HCT 中发挥重要作用。尽管随着 PTCy 的应用,单倍体-HCT 的使用有所增加,但仍存在一些悬而未决的问题。本研究的目的是研究 PTCy 后单倍体-HCT 不良结局的危险因素。这是在巴西的两个中心进行的回顾性研究。共纳入 103 例接受异基因、单倍体 HCT 伴 PTCy 的血液系统恶性肿瘤患者。移植时年龄(每增加 1 岁 HR=1.03;p=0.002)和高/极高疾病风险指数(DRI;HR=2.77;p=0.0007)以及母亲作为供者与其他供者相比是死亡的危险因素(HR=3.53;p=0.005)。多变量分析显示,年龄较大(HR=1.02;p=0.006)、高/极高 DRI(HR=2.39;p=0.003)和母亲作为供者与其他供者相比(HR=3.18;p=0.006)的患者,PFS 明显较差。高/极高 DRI(HR=4.01;p=0.002)和母亲作为供者与其他供者相比(HR=2.52;p=0.05)的患者复发率较高。年龄较大(HR=1.03 每年;p=0.03)的患者 NRM 较高。与环孢素相比,他克莫司是 II-IV 级移植物抗宿主病(GVHD)的保护因素(HR=0.46;p=0.04)。外周血(PBSC)是 cGVHD 的危险因素(HR=3.48;p=0.006),而他克莫司具有保护作用(HR=0.30;p=0.009)。与其他供者相比,母亲作为供者也是 OS、PFS 和复发较差的危险因素,提示应避免这种组合。他克莫司对 II-IV 级 aGVHD 和 cGVHD 均有保护作用,提示他克莫司在预防 GVHD 方面可能比环孢素更有效。PBSC 是 cGVHD 的危险因素,但对复发无影响。期待进行比较他克莫司与环孢素的前瞻性研究。

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