Department of Hematology, Kanagawa Cancer Center, Yokohama, Japan.
Blood Disorders Center, Aiiku Hospital, Sapporo, Japan.
Transplant Cell Ther. 2022 Jun;28(6):321.e1-321.e8. doi: 10.1016/j.jtct.2022.03.009. Epub 2022 Mar 13.
The global standard therapy for chronic myeloid leukemia (CML) is tyrosine kinase inhibitors (TKIs). One of the causes of therapeutic resistance to some TKIs corresponds to point mutations in the BCR-ABL1 fusion gene. Allogeneic hematopoietic cell transplantation (HCT) is a treatment option for high-risk CML, including TKI resistance. Although BCR-ABL1 point mutations comprise a major factor in the assessment of the indications for HCT, there is limited evidence for their significance in relation to transplant outcomes. This study aimed to evaluate the profiles and transplant outcomes of BCR-ABL1 mutations in allografted patients with CML. The retrospective study used a nationwide registry data including adult patients with CML who underwent their first HCT between 2006 and 2016. The inclusion criterion was the evaluation of the status of the BCR-ABL1 mutation before HCT. The cohort included 315 patients with a median age of 44 years (range 16-70 years). Point mutations were detected in 152 patients, of which 101 (66%) harbored T315I mutations and 51 harbored mutations other than T315I (non-T315I). With a median follow-up period of 38 months (range 2-114 months), overall survival (OS) at 3 years was worse in the mutation group than in the no-mutation group (53% versus 71%; P = .002), which was validated by multivariate analysis (hazard ratio [HR] = 1.50; 95% confidence interval [CI], 1.0-2.2; P = .038); this difference was remarkable in the chronic phase of CML. OS in the non-T315I group was significantly worse than that in the no-mutation group (HR = 1.69; 95% CI, 1.0-2.8; P = .035). The nationwide study has successfully evaluated the BCR-ABL1 mutational profile and its outcomes in patients with CML who received HCT. The mortality risk was significantly higher in patients with the BCR-ABL1 mutation than in patients without the mutation. These findings would be useful to understand the clinical significance of various BCR-ABL1 mutations in CML and provide insight into the on mid need for treatment strategies for cases of CML with BCR-ABL1 mutations.
全球慢性髓性白血病（CML）的标准治疗方法是酪氨酸激酶抑制剂（TKI）。一些 TKI 治疗耐药的原因对应于 BCR-ABL1 融合基因的点突变。异基因造血细胞移植（HCT）是高危 CML 的治疗选择，包括 TKI 耐药。尽管 BCR-ABL1 点突变是评估 HCT 适应证的一个重要因素，但关于其与移植结果的相关性的证据有限。本研究旨在评估 CML 异基因移植患者中 BCR-ABL1 突变的特征和移植结果。这项回顾性研究使用了一个全国性的登记数据，包括 2006 年至 2016 年间接受首次 HCT 的成人 CML 患者。纳入标准是在 HCT 前评估 BCR-ABL1 突变状态。该队列包括 315 名中位年龄为 44 岁（范围 16-70 岁）的患者。在 152 名患者中检测到点突变，其中 101 名（66%）携带 T315I 突变，51 名携带非 T315I 突变（非 T315I）。中位随访 38 个月（范围 2-114 个月）后，突变组的总生存（OS）明显差于无突变组（53%对 71%；P=0.002），这在多变量分析中得到了验证（风险比[HR]1.50；95%置信区间[CI]1.0-2.2；P=0.038）；在 CML 的慢性期差异显著。非 T315I 组的 OS 明显差于无突变组（HR 1.69；95%CI，1.0-2.8；P=0.035）。全国性研究成功评估了接受 HCT 的 CML 患者的 BCR-ABL1 突变谱及其结果。与无突变患者相比，BCR-ABL1 突变患者的死亡风险显著更高。这些发现有助于了解 CML 中各种 BCR-ABL1 突变的临床意义，并为了解 CML 中 BCR-ABL1 突变病例的治疗策略需求提供了深入的见解。
