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移植后环磷酰胺为基础的单倍体相合与同胞供者减低强度预处理移植治疗霍奇金淋巴瘤：降低移植物抗宿主病和复发风险。

Lower Graft-versus-Host Disease and Relapse Risk in Post-Transplant Cyclophosphamide-Based Haploidentical versus Matched Sibling Donor Reduced-Intensity Conditioning Transplant for Hodgkin Lymphoma.

机构信息

University of Texas, MD Anderson Cancer Center, Houston, Texas.

National Cancer Institute, National Institutes of Health, Bethesda, Maryland.

出版信息

Biol Blood Marrow Transplant. 2019 Sep;25(9):1859-1868. doi: 10.1016/j.bbmt.2019.05.025. Epub 2019 May 25.

DOI:10.1016/j.bbmt.2019.05.025
PMID:31132455
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6755039/
Abstract

Classic Hodgkin lymphoma (cHL) patients with relapsed or refractory disease may benefit from allogeneic hematopoietic cell transplantation (allo-HCT), but many lack a matched sibling donor (MSD). Herein, we compare outcomes of 2 reduced-intensity conditioning (RIC) HCT platforms in cHL: T cell-replete related donor haploidentical (haplo) HCT with a post-transplant cyclophosphamide (PTCy)-based approach versus an MSD/calcineurin inhibitor (CNI)-based approach. The study included 596 adult patients who underwent a first RIC allo-HCT for cHL between 2008 and 2016 using either a haplo-PTCy (n = 139) or MSD/CNI-based (n = 457) approach. Overall survival (OS) was the primary endpoint. Secondary endpoints included acute graft-versus-host disease (aGVHD) and chronic GVHD (cGVHD), nonrelapse mortality (NRM), relapse/progression, and progression-free survival (PFS). On multivariate analysis, there was no significant difference between haplo/PTCy and MDS/CNI-based approaches in terms of OS (hazard ratio [HR], 1.07; 95% confidence interval [CI], .79 to 1.45; P = .66) or PFS (HR, .86; 95% CI, .68 to 1.10; P = .22). Haplo/PTCy was associated with a significantly higher risk of grades II to IV aGVHD (odds ratio [OR], 1.73, 95% CI, 1.16 to 2.59; P = .007), but the risk of grades III to IV aGVHD was not significantly different between the 2 cohorts (OR, .61; 95% CI, .29 to 1.27; P = .19). The haplo/PTCy platform provided a significant reduction in cGVHD risk (HR, .45; 95% CI, .32 to .64; P < .001), and a significant reduction in relapse risk (HR, .74; 95% CI, .56 to .97; P = .03). There was a statistically nonsignificant trend toward higher NRM with a haplo/PTCy approach (HR, 1.65; 95% CI, .99 to 2.77; P = .06). Haplo/PTCy-based approaches are associated with lower incidences of cGVHD and relapse, with PFS and OS outcomes comparable with MSD/CNI-based approaches. There was a leaning toward higher NRM with a haplo/PTCy-based platform. These data show that haplo/PTCy allo-HCT in cHL results in survival comparable with MSD/CNI-based allo-HCT.

摘要

经典霍奇金淋巴瘤（cHL）患者在复发或难治时可能受益于同种异体造血细胞移植（allo-HCT），但许多患者缺乏匹配的同胞供体（MSD）。在此，我们比较了两种用于 cHL 的降低强度预处理（RIC）allo-HCT 平台的结果：T 细胞丰富相关供体单倍体（haplo）HCT 联合移植后环磷酰胺（PTCy）方案与 MSD/钙调磷酸酶抑制剂（CNI）方案。该研究纳入了 2008 年至 2016 年间接受首次 RIC allo-HCT 治疗的 596 例成人 cHL 患者，分别采用 haplo-PTCy（n=139）或 MSD/CNI 方案（n=457）。主要终点为总生存（OS）。次要终点包括急性移植物抗宿主病（aGVHD）和慢性移植物抗宿主病（cGVHD）、非复发死亡率（NRM）、复发/进展和无进展生存（PFS）。多因素分析显示，haplo/PTCy 与 MSD/CNI 方案在 OS（风险比[HR]，1.07；95%置信区间[CI]，0.79 至 1.45；P=0.66）或 PFS（HR，0.86；95%CI，0.68 至 1.10；P=0.22）方面无显著差异。haplo/PTCy 与 II 至 IV 级 aGVHD 的风险显著升高（比值比[OR]，1.73，95%CI，1.16 至 2.59；P=0.007），但两组间 III 至 IV 级 aGVHD 的风险无显著差异（OR，0.61；95%CI，0.29 至 1.27；P=0.19）。haplo/PTCy 方案可显著降低 cGVHD 风险（HR，0.45；95%CI，0.32 至 0.64；P<0.001），并显著降低复发风险（HR，0.74；95%CI，0.56 至 0.97；P=0.03）。与 haplo/PTCy 方案相比，NRM 呈统计学上的非显著增高趋势（HR，1.65；95%CI，0.99 至 2.77；P=0.06）。haplo/PTCy 方案与 MSD/CNI 方案相比，cGVHD 和复发的发生率较低，PFS 和 OS 结果相当。haplo/PTCy 方案与更高的 NRM 倾向相关。这些数据表明，haplo/PTCy 用于 cHL 的 allo-HCT 可产生与 MSD/CNI 为基础的 allo-HCT 相当的生存获益。

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[2]
Outcomes of Allogeneic Stem Cell Transplant in Patients with Relapsed/Refractory Hodgkin Lymphoma.

Curr Oncol. 2025-2-18

[3]
When to use stem cell transplantation for classical Hodgkin lymphoma.

Hematology Am Soc Hematol Educ Program. 2024-12-6

[4]
Optimization of T-cell-replete haploidentical hematopoietic stem cell transplantation: the Chinese experience.

Haematologica. 2025-3-1

[5]
PTCy-based graft-versus-host disease prophylaxis for matched sibling donor allogeneic hematopoietic cell transplantation.

Blood Adv. 2025-2-11

[6]
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[8]
Peripheral blood stem cell transplantation using HLA-haploidentical donor with post-transplant cyclophosphamide versus HLA-matched sibling donor for lymphoma.

Bone Marrow Transplant. 2024-5

[9]
Severity and organ distribution of chronic graft-versus-host disease with posttransplant cyclophosphamide-based versus methotrexate/calcineurin inhibitor-based allogeneic hematopoietic cell transplantation.

Bone Marrow Transplant. 2024-3

[10]
Optimizing Treatment for Relapsed/Refractory Classic Hodgkin Lymphoma in the Era of Immunotherapy.

Cancers (Basel). 2023-9-11

本文引用的文献

[1]
Recommendations for managing PD-1 blockade in the context of allogeneic HCT in Hodgkin lymphoma: taming a necessary evil.

Blood. 2018-5-2

[2]
Nivolumab for Relapsed/Refractory Classic Hodgkin Lymphoma After Failure of Autologous Hematopoietic Cell Transplantation: Extended Follow-Up of the Multicohort Single-Arm Phase II CheckMate 205 Trial.

J Clin Oncol. 2018-3-27

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Bone Marrow Transplant. 2018-4

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Biol Blood Marrow Transplant. 2017-11-29

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Post-Transplantation Cyclophosphamide-Based Haploidentical Transplantation as Alternative to Matched Sibling or Unrelated Donor Transplantation for Hodgkin Lymphoma: A Registry Study of the Lymphoma Working Party of the European Society for Blood and Marrow Transplantation.

J Clin Oncol. 2017-8-28

[7]
Mobilized Peripheral Blood Stem Cells Versus Unstimulated Bone Marrow As a Graft Source for T-Cell-Replete Haploidentical Donor Transplantation Using Post-Transplant Cyclophosphamide.

J Clin Oncol. 2017-9-10

[8]
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Blood. 2017-7-13

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Bone Marrow Transplant. 2017-5

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Blood. 2017-3-9

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