Bone Marrow Transplantation Program, Department of Internal Medicine, American University of Beirut Medical Center, Beirut, Lebanon.
EBMT Statistical Unit, Saint Antoine Hospital, Sorbonne University, Paris, France.
Bone Marrow Transplant. 2024 Sep;59(9):1239-1246. doi: 10.1038/s41409-024-02300-8. Epub 2024 Jun 4.
T-cell acute lymphoblastic leukemia (T-ALL) predominantly affects individuals in late childhood and young adulthood. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a curative modality particularly in the setting of poor risk genetics and/or persistent minimal residual disease. Limited studies have directly explored the impact of patient- and transplant-related factors on post-transplant outcomes in T-ALL. Using a large dataset from the European Society for Blood and Marrow Transplantation registry, we identified 1907 adult T-ALL patients (70% male) who underwent their first allo-HSCT in first complete remission (CR1) from matched sibling donors (MSD; 45%), unrelated donors (UD; 43%) or haploidentical donors (12%) between 2010 and 2021. The median age at transplant was 33.4 years (18.1-75). The median follow up was 2.9 years. Most patients underwent total body irradiation (TBI)-based myeloablative conditioning (69%). The 2-year overall survival (OS) was 69.4%, and leukemia -free survival (LFS) was 62.1%. In multivariate analysis, advanced age at transplant negatively affected LFS (for each 10-year increment, HR = 1.11, p = 0.004), GVHD-free, relapse-free survival (GRFS) (HR = 1.06, p = 0.04), OS (HR = 1.12, p = 0.002), and non-relapse mortality (NRM) (HR = 1.23, p < 0.001). More recent years of allo-HSCT were associated with improved GFRS (For each 3-year increment, HR = 0.89, p < 0.001), OS (HR = 0.9, p = 0.02), and decreased NRM (HR = 0.82, p = 0.008). TBI improved LFS. (HR = 0.79, p = 0.02), GRFS (HR = 0.83, p = 0.04), and relapse incidence (RI) (HR = 0.65, p < 0.001). Female-to-male transplant negatively affected GRFS (HR = 1.21, p = 0.02) and OS (HR = 1.23, p = 0.048). In vivo T-cell depletion significantly improved GFRS (HR = 0.74, p < 0.001). This large study identified prognostic factors, such as age at transplant conditioning regimen, in influencing post-transplant in adult T-ALL patients undergoing allo-HSCT. Importantly, a significant improvement over time was noted. These findings hold great promise for new adapted treatment strategies and can serve as a benchmark for future studies in that setting.
T 细胞急性淋巴细胞白血病（T-ALL）主要影响儿童晚期和青年期的个体。同种异体造血干细胞移植（allo-HSCT）是一种治愈方法，特别是在遗传风险高和/或持续存在微小残留疾病的情况下。有限的研究直接探讨了患者和移植相关因素对 T-ALL 患者移植后结局的影响。利用欧洲血液和骨髓移植协会注册中心的一个大型数据集，我们确定了 1907 例成年 T-ALL 患者（70%为男性），他们在 2010 年至 2021 年间在首次完全缓解（CR1）期从匹配的同胞供体（MSD；45%）、无关供体（UD；43%）或单倍体供体（12%）接受了他们的首次 allo-HSCT。移植时的中位年龄为 33.4 岁（18.1-75 岁）。中位随访时间为 2.9 年。大多数患者接受了基于全身照射（TBI）的清髓性预处理（69%）。2 年总生存率（OS）为 69.4%，无白血病生存率（LFS）为 62.1%。多变量分析显示，移植时年龄较大对 LFS 有负面影响（每增加 10 岁，HR=1.11，p=0.004）、GVHD 无复发生存率（GRFS）（HR=1.06，p=0.04）、OS（HR=1.12，p=0.002）和非复发死亡率（NRM）（HR=1.23，p<0.001）。较近年份的 allo-HSCT 与改善的 GFRS 相关（每增加 3 年，HR=0.89，p<0.001）、OS（HR=0.9，p=0.02）和降低的 NRM（HR=0.82，p=0.008）。TBI 改善了 LFS（HR=0.79，p=0.02）、GRFS（HR=0.83，p=0.04）和复发率（RI）（HR=0.65，p<0.001）。女性对男性的移植对 GRFS（HR=1.21，p=0.02）和 OS（HR=1.23，p=0.048）有负面影响。体内 T 细胞耗竭显著改善了 GFRS（HR=0.74，p<0.001）。这项大型研究确定了一些预后因素，如移植时的年龄和预处理方案，这些因素会影响接受 allo-HSCT 的成年 T-ALL 患者的移植后结果。重要的是，我们注意到随着时间的推移有显著的改善。这些发现为新的适应性治疗策略提供了巨大的希望，并可以作为该领域未来研究的基准。
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