Division of Hematology, Jichi Medical University Saitama Medical Center, Saitama.
Division of Hematology, Jichi Medical University Saitama Medical Center, Saitama, Japan; Division of Emerging Medicine for Integrated Therapeutics (EMIT), Center for Molecular Medicine, Jichi Medical University, Shimotsuke.
Haematologica. 2024 Nov 1;109(11):3593-3601. doi: 10.3324/haematol.2024.285256.
The recent progress with ruxolitinib treatment might improve quality of life as well as overall survival in patients with primary myelofibrosis. Therefore, the optimal timing of allogeneic hematopoietic cell transplantation (HCT) in the ruxolitinib era remains to be elucidated. We constructed a Markov model to simulate the 5-year clinical course of transplant candidates with primary myelofibrosis and compared outcomes between those who underwent immediate HCT and those whose HCT was delayed until after ruxolitinib failure. Since older age was associated with an increased risk of mortality, we analyzed patients aged <60 and ≥60 years separately in subgroup analyses. Life expectancy was consistently longer in the groups undergoing delayed HCT after ruxolitinib failure regardless of the patients' age. Regarding quality-adjusted life years, a baseline analysis showed that immediate HCT was inferior to delayed HCT after ruxolitinib failure (2.19 vs. 2.26). In patients aged <60 years, immediate HCT was equivalent to delayed HCT after ruxolitinib failure (2.31 vs. 2.31). On the other hand, in patients aged ≥60 years, immediate HCT was inferior to delayed HCT after ruxolitinib failure (1.98 vs. 2.21). A one-way sensitivity analysis showed that the utility of being alive without chronic graft-versus-host disease after immediate HCT was the most influential parameter for quality-adjusted life years, and that a value higher than 0.836 could reverse the superiority of delayed HCT after ruxolitinib failure. As a result, delayed HCT after ruxolitinib failure is expected to be superior to immediate HCT, especially in patients aged ≥60 years, and is also a promising strategy even in those aged <60 years.
芦可替尼治疗的最新进展可能会改善原发性骨髓纤维化患者的生活质量和总体生存率。因此，在芦可替尼时代，异体造血细胞移植（HCT）的最佳时机仍有待阐明。我们构建了一个马尔可夫模型来模拟原发性骨髓纤维化移植候选者的 5 年临床病程，并比较了立即进行 HCT 与在芦可替尼治疗失败后延迟 HCT 的患者的结局。由于年龄较大与死亡率增加相关，我们在亚组分析中分别分析了年龄<60 岁和≥60 岁的患者。无论患者年龄如何，在芦可替尼治疗失败后延迟 HCT 的患者的预期寿命始终更长。关于质量调整生命年，基线分析表明，立即进行 HCT 不如在芦可替尼治疗失败后延迟 HCT（2.19 比 2.26）。在年龄<60 岁的患者中，立即进行 HCT 与在芦可替尼治疗失败后延迟 HCT 相当（2.31 比 2.31）。另一方面，在年龄≥60 岁的患者中，立即进行 HCT 不如在芦可替尼治疗失败后延迟 HCT（1.98 比 2.21）。单向敏感性分析表明，在立即进行 HCT 后无慢性移植物抗宿主病的生存效用是质量调整生命年的最具影响力的参数，并且该值高于 0.836 可以逆转在芦可替尼治疗失败后延迟 HCT 的优势。因此，在芦可替尼治疗失败后延迟 HCT 预计优于立即进行 HCT，尤其是在年龄≥60 岁的患者中，即使在年龄<60 岁的患者中也是一种有前途的策略。
