Department of Hematologic Oncology and Blood Disorders, Levine Cancer Institute, Atrium Health, Charlotte, North Carolina.
Department of Myeloma and Lymphoma, University of Texas, MD Anderson Cancer Center, Houston.
JAMA Oncol. 2020 Jul 1;6(7):1011-1018. doi: 10.1001/jamaoncol.2020.1278.
Reduced-intensity conditioning and nonmyeloablative conditioning (RIC-NMAC) regimens are frequently used in allogeneic hematopoietic cell transplant (HCT) for non-Hodgkin lymphoma. However, the optimal RIC-NMAC regimen in allogeneic HCT for non-Hodgkin lymphoma is not known.
To investigate whether RIC-NMAC regimens at a higher end of the intensity spectrum are associated with increased nonrelapse mortality and lower overall survival compared with RIC-NMAC regimens at the lower end of the intensity spectrum in patients with non-Hodgkin lymphoma undergoing allogeneic HCT.
DESIGN, SETTING, AND PARTICIPANTS: This cohort study used data from 1823 adult patients with non-Hodgkin lymphoma in the Center for International Blood and Marrow Transplant Research registry. Included patients underwent allogeneic HCT using matched related or unrelated donors between January 2008 and December 2016. Statistical analysis was performed from June 1, 2019, to February 10, 2020.
Patients received 1 of 4 RIC-NMAC regimens: fludarabine-intravenous busulfan (Flu-Bu), approximately 6.4 mg/kg (n = 458); fludarabine-melphalan (Flu-Mel140), 140 mg/m2 (n = 885); fludarabine-cyclophosphamide (Flu-Cy) (n = 391); or Flu-Cy with 2 Gy total body irradiation (Flu-Cy-2GyTBI) (n = 89).
The primary outcome was overall survival. Secondary outcomes were nonrelapse mortality, incidence of relapse, progression-free survival, and the incidence of acute and chronic graft-vs-host disease (GVHD).
Of 1823 patients, 1186 (65%) were male, with a mean (SD) age of 54.8 (9.9) years. The 4-year adjusted OS was 58% in the Flu-Bu cohort, 67% in the Flu-Cy-2GyTBI cohort, 49% in the Flu-Mel140 cohort, and 63% in the Flu-Cy cohort (P < .001). After adjustment for age, Karnofsky performance score, HCT comorbidity index, NHL subtype, remission status at HCT, and the use of antithymocyte globulin or alemtuzumab, the regression analysis showed a significantly higher mortality risk associated with Flu-Mel140 compared with Flu-Bu (hazard ratio [HR], 1.34; 95% CI, 1.13-1.59; P < .001). Compared with the Flu-Cy cohort, the Flu-Mel140 cohort had a higher risk of chronic GVHD (HR, 1.38; 95% CI, 1.15-1.65; P < .001). The Flu-Mel140 regimen was associated with a higher nonrelapse mortality risk (HR, 1.78; 95% CI, 1.37-2.31; P < .001) compared with the Flu-Bu regimen.
The findings suggest that use of the more intense RIC-NMAC regimen, Flu-Mel140, may have a negative association with overall survival and may be associated with higher nonrelapse mortality. The Flu-Bu and Flu-Cy regimens with or without 2GyTBI regimens appeared to provide comparable overall survival.
在异基因造血细胞移植（HCT）中，对于非霍奇金淋巴瘤，常采用低强度预处理和非清髓性预处理（RIC-NMAC）方案。然而，非霍奇金淋巴瘤异基因 HCT 中最佳的 RIC-NMAC 方案尚不清楚。
研究在非霍奇金淋巴瘤患者中，与 RIC-NMAC 方案低强度端相比，RIC-NMAC 方案高强度端是否与非复发死亡率增加和总体生存率降低相关，这些患者接受异基因 HCT。
设计、设置和参与者：本队列研究使用了国际血液和骨髓移植研究中心注册处的 1823 名非霍奇金淋巴瘤成年患者的数据。纳入的患者在 2008 年 1 月至 2016 年 12 月期间使用匹配的相关或无关供体接受了异基因 HCT。统计分析于 2019 年 6 月 1 日至 2020 年 2 月 10 日进行。
患者接受了 4 种 RIC-NMAC 方案之一：氟达拉滨静脉用白消安（Flu-Bu），约 6.4mg/kg（n=458）；氟达拉滨-美法仑（Flu-Mel140），140mg/m2（n=885）；氟达拉滨-环磷酰胺（Flu-Cy）（n=391）；或氟达拉滨-环磷酰胺联合 2Gy 全身照射（Flu-Cy-2GyTBI）（n=89）。
主要结局是总生存率。次要结局是无复发死亡率、复发率、无进展生存率以及急性和慢性移植物抗宿主病（GVHD）的发生率。
在 1823 名患者中，1186 名（65%）为男性，平均（SD）年龄为 54.8（9.9）岁。Flu-Bu 队列的 4 年调整 OS 为 58%，Flu-Cy-2GyTBI 队列为 67%，Flu-Mel140 队列为 49%，Flu-Cy 队列为 63%（P<0.001）。在调整年龄、Karnofsky 表现评分、HCT 合并症指数、NHL 亚型、HCT 时的缓解状态、使用抗胸腺细胞球蛋白或阿仑单抗后，回归分析显示 Flu-Mel140 与 Flu-Bu 相比，死亡率风险显著增加（HR，1.34；95%CI，1.13-1.59；P<0.001）。与 Flu-Cy 队列相比，Flu-Mel140 队列发生慢性 GVHD 的风险更高（HR，1.38；95%CI，1.15-1.65；P<0.001）。与 Flu-Bu 方案相比，Flu-Mel140 方案与非复发死亡率风险增加相关（HR，1.78；95%CI，1.37-2.31；P<0.001）。
研究结果表明，使用更强烈的 RIC-NMAC 方案（Flu-Mel140）可能与总体生存率呈负相关，并且可能与非复发死亡率增加有关。Flu-Bu 和 Flu-Cy 方案联合或不联合 2GyTBI 方案似乎提供了相当的总体生存率。
