Introduction

Disease relapse is the most common cause of therapy failure in NHL patients undergoing RIC alloHCT. Whether increasing TBI dose from 2Gy to 4Gy in RIC-platform can provide improved disease control without increasing non-relapse mortality (NRM) is not known. Using the CIBMTR database we evaluated the outcomes of NHL patients receiving RIC alloHCT with either Flu/2Gy TBI vs. Flu/4Gy TBI.

Methods

In the CIBMTR registry, 413 adult NHL patients underwent a first alloHCT using either a matched related or unrelated donor between 2008-2017, utilizing a RIC regimen with either Flu/2Gy TBI (n=349) or Flu/4Gy TBI (n=64). Graft-versus-host disease (GVHD) prophylaxis was calcineurin inhibitor-based. The primary endpoint was overall survival (OS). Secondary endpoints included acute (a) and chronic (c) GVHD, NRM, relapse/progression and progression-free survival (PFS). Probabilities of OS and PFS were calculated using the Kaplan-Meier estimator. Multivariable regression analysis was performed for GVHD, relapse/progression, NRM, PFS, and OS. Covariates with a p<0.05 were considered significant.

Results

Baseline characteristics are shown in Figure 1. The Flu/2Gy TBI cohort had significantly fewer patients with KPS ≥90 and significantly more patients with HCT-CI ≥3. On multivariate analysis (Figure 2), the two conditioning cohorts were not significantly different in terms of risk of grade 3-4 aGVHD or cGVHD. Compared to Flu/2Gy TBI, the Flu/4Gy TBI conditioning was associated with a significantly higher risk of NRM (HR 1.79, 95%CI=1.11-2.89, p = 0.02), and inferior OS (HR 1.51, 95%CI=1.03-2.23, p = 0.03). No significant differences were seen in the risk of relapse/progression (HR 0.78, 95%CI=0.47-1.29, p = 0.33) or PFS (HR 1.09, 95%CI=0.78-1.54, p=0.61) between the two regimens. Comparing Flu/2Gy TBI vs. Flu/4Gy TBI cohorts the 5-year adjusted outcomes were; NRM (28% vs. 47%; p = 0.005), relapse/progression (35% vs. 29%; p = 0.28), PFS (37% vs. 24%; p = 0.03) and OS (51% vs. 31%; p = 0.001), respectively (Figure 3). Rate of graft failure at day100 in similar order was 0.6% vs. 1.6% (p = 0.54), respectively. Relapse was the most common cause of death in both cohorts.

Conclusions

In NHL patients undergoing Flu/TBI-based conditioning, augmenting TBI dose from 2Gy to 4Gy is associated with higher NRM and inferior OS, without any significant benefit in terms of disease control. 2Gy is optimal dose in the RIC Flu/TBI platform for lymphomas.

中文翻译：

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在接受异基因造血细胞移植（alloHCT）的非霍奇金淋巴瘤（NHL）患者中，氟达拉滨（Flu）/基于TBI的降低强度调节（RIC）方案中较高的全身辐射（TBI）剂量与较低的生存率相关。

介绍

在接受RIC alloHCT的NHL患者中，疾病复发是治疗失败的最常见原因。尚不知道在RIC平台中将TBI剂量从2Gy增加到4Gy是否可以改善疾病控制而不增加非复发死亡率（NRM）。使用CIBMTR数据库，我们评估了使用flu / 2Gy TBI与Flu / 4Gy TBI接受RIC alloHCT的NHL患者的预后。

方法

在CIBMTR注册中心，2008年至2017年之间，使用匹配的相关或不相关供体，对413名成年NHL患者进行了首次alloHCT，采用RIC方案结合Flu / 2Gy TBI（n = 349）或Flu / 4Gy TBI（n = 64）。 ）。预防移植物抗宿主病（GVHD）是基于钙调神经磷酸酶抑制剂的。主要终点是总体生存期（OS）。次要终点包括急性（a）和慢性（c）GVHD，NRM，复发/进展和无进展生存期（PFS）。使用Kaplan-Meier估计器计算OS和PFS的概率。对GVHD，复发/进展，NRM，PFS和OS进行了多变量回归分析。p <0.05的协变量被认为是显着的。

结果

基线特征如图1所示。Flu/ 2Gy TBI队列中KPS≥90的患者明显减少，而HCT-CI≥3的患者明显更多。在多变量分析中（图2），两个条件队列在3-4级aGVHD或cGVHD的风险方面无显着差异。与Flu / 2Gy TBI相比，Flu / 4Gy TBI调理与NRM的风险显着较高（HR 1.79，95％CI = 1.11-2.89，p = 0.02）和OS较低（HR 1.51，95％CI = 1.03-2.23，p ＝ 0.03）。两种方案在复发/进展风险（HR 0.78，95％CI = 0.47-1.29，p = 0.33）或PFS（HR 1.09，95％CI = 0.78-1.54，p = 0.61）方面无显着差异。比较Flu / 2Gy TBI与Flu / 4Gy TBI队列的5年调整结局。NRM（28％vs. 47％; p = 0.005），复发/进展（35％vs. 29％; p = 0.28），PFS（37％vs. 24％；p = 0.03）和OS（分别为51％和31％； p = 0.001）（图3）。在第100天，移植失败率以相似的顺序分别为0.6％和1.6％（p = 0.54）。复发是两个队列中最常见的死亡原因。

结论

在接受基于Flu / TBI的调理的NHL患者中，将TBI剂量从2Gy增加到4Gy与更高的NRM和较差的OS相关，在疾病控制方面没有任何明显的益处。在RIC Flu / TBI平台中，2Gy是淋巴瘤的最佳剂量。