Allogeneic hematopoietic cell transplantation (HCT) offers a potential cure in Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL); nonetheless, relapses are common and the major cause of mortality. One strategy to prevent relapse is tyrosine kinase inhibitor (TKI) maintenance post-HCT, but published clinical experience is primarily with the first-generation TKI imatinib while data with newer generation TKIs are limited. We conducted a retrospective analysis of 185 Ph+ ALL patients who underwent HCT followed by TKI maintenance from 2003 to 2021 at City of Hope. Initially, 50 (27.0%) received imatinib, 118 (63.8%) received a second-generation TKI (2G-TKI), and 17 (9.2%) received ponatinib. A total of 77 patients (41.6%) required a dose reduction of their initial TKI due to toxicity. Sixty-six patients (35.7%) did not complete maintenance due to toxicity; 69 patients (37.3%) discontinued 1 TKI, and 11 (5.9%) discontinued 2 TKIs due to toxicity. Initial imatinib versus 2G-TKI versus ponatinib maintenance was discontinued in 19 (38.0%) versus 68 (57.6%) versus 3 (17.6%) patients due to toxicity (p = .003), respectively. Patients on ponatinib as their initial TKI had a longer duration of TKI maintenance versus 2G-TKI: 576.0 days (range, 72–921) versus 254.5 days (range, 3–2740; p = .02). The most common reasons for initial TKI discontinuation include gastrointestinal (GI) intolerance (15.1%), cytopenia (8.6%), and fluid retention (3.8%). The 5-year overall survival and progression-free survival for the total population were 78% and 71%, respectively. Our findings demonstrate the challenges of delivering post-HCT TKI maintenance in a large real-world cohort as toxicities leading to TKI interruptions, discontinuation, and dose reduction were common.

中文翻译：

---

费城染色体阳性急性淋巴细胞白血病同种异体造血细胞移植后维持酪氨酸激酶抑制剂的相关毒性


同种异体造血细胞移植（HCT）为费城染色体阳性（Ph+）急性淋巴细胞白血病（ALL）提供了潜在的治愈方法；然而，复发很常见，并且是死亡的主要原因。预防复发的一种策略是 HCT 后维持酪氨酸激酶抑制剂 (TKI)，但已发表的临床经验主要是第一代 TKI 伊马替尼，而新一代 TKI 的数据有限。我们对 2003 年至 2021 年在 City of Hope 接受 HCT 后接受 TKI 维持治疗的 185 名 Ph+ ALL 患者进行了回顾性分析。最初，50 例（27.0%）接受伊马替尼治疗，118 例（63.8%）接受第二代 TKI（2G-TKI）治疗，17 例（9.2%）接受帕纳替尼治疗。共有 77 名患者 (41.6%) 由于毒性需要减少初始 TKI 剂量。 66 名患者（35.7%）因毒性而未完成维持治疗； 69 名患者 (37.3%) 停用 1 种 TKI，11 名患者 (5.9%) 因毒性停用 2 种 TKI。初始伊马替尼、2G-TKI 和帕纳替尼维持治疗分别有 19 名 (38.0%)、68 名 (57.6%) 和 3 名 (17.6%) 患者因毒性而停止 ( p = 0.003)。与 2G-TKI 相比，接受普纳替尼作为初始 TKI 的患者的 TKI 维持时间更长：576.0 天（范围，72-921）对比 254.5 天（范围，3-2740； p = .02）。最初停止 TKI 的最常见原因包括胃肠道 (GI) 不耐受 (15.1%)、血细胞减少 (8.6%) 和液体潴留 (3.8%)。总人群的 5 年总生存率和无进展生存率分别为 78% 和 71%。 我们的研究结果表明，在大型现实世界队列中提供 HCT 后 TKI 维持治疗面临着挑战，因为导致 TKI 中断、停药和剂量减少的毒性很常见。