Department of Hematology, Kyoto University Hospital, Kyoto, Japan.
Department of Hematology and Oncology, Nagoya University Graduate School of Medicine, Nagoya, Aichi, Japan.
Hematol Oncol. 2022 Aug;40(3):442-456. doi: 10.1002/hon.3000. Epub 2022 Apr 12.
The introduction of tyrosine kinase inhibitors (TKIs) in chronic myeloid leukemia (CML) treatment has dramatically improved the prognosis of CML patients and reduced the number of patients receiving allogeneic stem cell transplantation (allo-SCT). However, the impact of the newest-generation TKIs on the overall survival (OS) after allo-SCT has not been well described. To investigate the beneficial effects of TKIs on the prognosis after allo-SCT, we conducted a retrospective observational study using the Transplant Registry Unified Management Program database in Japan. We analyzed 1188 patients (male/female: 738/450; median age: 44 years; range: 16-75) who underwent their first allo-SCT between January 2001 and December 2018. We divided the patients into two groups according to the TKI treatment used before allo-SCT: group 1 was treated with the first generation TKI imatinib; group 2 was treated with the second generation TKIs nilotinib, dasatinib, or bosutinib and/or the third generation TKI ponatinib. We compared the post allo-SCT OS between the two groups. The 3-year OS rates (95%CI) of groups 1 and 2 were 59.3% (54.8%-63.5%) and 65.8% (61.6%-69.6%), respectively (p = 0.017). Multivariate analysis confirmed that group 2 had superior OS after allo-SCT compared to group 1 (p = 0.002). Other factors associated with superior prognosis were age ≤65, performance status (PS) 0/1, a 6/6 HLA-matched donor and chronic-phase (CP) disease status at allo-SCT. A subgroup analysis showed poor prognoses for patients who could not obtain a molecular response before allo-SCT and patients with positive T315I mutation in the BCR/ABL gene. In group 2, early allo-SCT was correlated with superior OS in patients with a blast-crisis disease status at allo-SCT (p = 0.001). The cumulative incidence of non-relapse mortality rate significantly decreased in group 2 (p = 0.0005). The post allo-SCT OS was improved both by pre- and post-management of allo-SCT and by the introduction of newer TKIs.
酪氨酸激酶抑制剂 (TKI) 在慢性髓性白血病 (CML) 治疗中的引入极大地改善了 CML 患者的预后，并减少了接受异基因造血干细胞移植 (allo-SCT) 的患者数量。然而，最新一代 TKI 对 allo-SCT 后总生存 (OS) 的影响尚未得到很好的描述。为了研究 TKI 对 allo-SCT 后预后的有益影响，我们使用日本移植登记统一管理计划数据库进行了回顾性观察研究。我们分析了 1188 例 (男/女：738/450；中位年龄：44 岁；范围：16-75) 于 2001 年 1 月至 2018 年 12 月期间首次接受 allo-SCT 的患者。我们根据 allo-SCT 前使用的 TKI 治疗将患者分为两组：组 1 接受第一代 TKI 伊马替尼治疗；组 2 接受第二代 TKI 尼洛替尼、达沙替尼或博舒替尼和/或第三代 TKI 泊那替尼治疗。我们比较了两组患者 allo-SCT 后的 OS。组 1 和组 2 的 3 年 OS 率 (95%CI) 分别为 59.3% (54.8%-63.5%) 和 65.8% (61.6%-69.6%)，差异有统计学意义 (p=0.017)。多变量分析证实，与组 1 相比，组 2 在 allo-SCT 后具有更好的 OS(p=0.002)。其他与预后较好相关的因素包括年龄≤65 岁、表现状态 (PS) 0/1、6/6 HLA 匹配供体和 allo-SCT 时处于慢性期 (CP) 疾病状态。亚组分析显示，allo-SCT 前无法获得分子反应的患者和 BCR/ABL 基因中存在 T315I 突变的患者预后较差。在组 2 中，早期 allo-SCT 与 allo-SCT 时处于急变期疾病状态的患者的 OS 改善相关 (p=0.001)。非复发死亡率的累积发生率在组 2 中显著降低 (p=0.0005)。allo-SCT 前后的管理以及新型 TKI 的引入均改善了 allo-SCT 后的 OS。
