Department of Hematology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China.
Department of Hematology, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, China.
Leukemia. 2021 Jul;35(7):2054-2063. doi: 10.1038/s41375-020-01090-4. Epub 2020 Nov 17.
Relapse is a major cause of treatment failure in Philadelphia-chromosome-positive acute lymphoblastic leukemia (Ph+ALL) undergoing allogeneic hematopoietic cell transplantation (allo-HCT). This study aimed to evaluate the effect of a new pre-emptive tyrosine kinase inhibitors (TKIs) strategy on relapse in Ph+ALL patients with complete remission undergoing allo-HCT. Pre-emptive TKIs initiation was based on BCR/ABL molecular monitoring. TKIs choice was based on BCR/ABL mutations. Donor lymphocyte infusion was recommended in those with poor response to TKIs. Prophylactic TKIs from historical data were as control. The primary endpoint was relapse. One hundred and sixty-seven Ph+ALL patients were enrolled in this study, including 103 in the pre-emptive group and 64 in the prophylactic group. The 3-year cumulative incidence of relapse was 11% and 31% in the pre-emptive and prophylactic groups (P = 0.001), respectively. The 3-year overall survival (OS) was 87% and 66% (P = 0.001), and leukemia-free survival (LFS) was 83% and 61% (P = 0.000), respectively, in the pre-emptive and prophylactic groups. Multivariate analysis showed that the pre-emptive strategy was the protective factor for relapse, OS, and LFS (P = 0.005, P = 0.005, and P = 0.003, respectively). Our data suggest that this new pre-emptive TKIs strategy based on BCR/ABL molecular monitoring might reduce relapse and improve survival for Ph+ALL patients undergoing allo-HCT. ClinicalTrials.Gov Identifier (NCT01883219).
复发是接受异基因造血细胞移植（allo-HCT）的费城染色体阳性急性淋巴细胞白血病（Ph+ALL）治疗失败的主要原因。本研究旨在评估在接受 allo-HCT 的完全缓解的 Ph+ALL 患者中，新的抢先酪氨酸激酶抑制剂（TKI）策略对复发的影响。抢先 TKI 启动基于 BCR/ABL 分子监测。TKI 的选择基于 BCR/ABL 突变。对于 TKI 反应不佳的患者，建议进行供者淋巴细胞输注。来自历史数据的预防性 TKI 作为对照。主要终点是复发。本研究共纳入 167 例 Ph+ALL 患者，其中抢先组 103 例，预防性组 64 例。抢先组和预防性组的 3 年累积复发率分别为 11%和 31%（P=0.001）。抢先组和预防性组的 3 年总生存率（OS）分别为 87%和 66%（P=0.001），无白血病生存率（LFS）分别为 83%和 61%（P=0.000）。多变量分析表明，抢先策略是复发、OS 和 LFS 的保护因素（P=0.005、P=0.005 和 P=0.003）。我们的数据表明，这种基于 BCR/ABL 分子监测的新的抢先 TKI 策略可能降低 Ph+ALL 患者接受 allo-HCT 后的复发率并提高生存率。ClinicalTrials.Gov 标识符（NCT01883219）。
