Aydin Semra, Schmitz Jennifer, Dellacasa Chiara M, Dogliotti Irene, Giaccone Luisa, Busca Alessandro
Department of Oncology, Hematology, Immuno-Oncology and Rheumatology, University Hospital of Bonn, 53127 Bonn, Germany.
Division of Hematology, Department of Oncology, AOU Città della Salute e della Scienza di Torino, 10126 Turin, Italy.
Cancers (Basel). 2024 Sep 4;16(17):3070. doi: 10.3390/cancers16173070.
Post-transplant relapse of acute myeloid leukemia and myelodysplastic syndrome faces restricted effective salvage regimens. We retrospectively analyzed the use of Azacitidine-donor lymphocyte infusion (AZA/DLI) in this setting. Furthermore, data on bone marrow Wilms tumor gene 1 (WT1) expression were collected. A Cox proportional hazards model, an outcome-oriented approach for the lowest smoothed plot of the martingale residuals, was performed for the cut-point determination of the respective WT1 expression levels. Finally, a Cox proportional hazards model investigated the association of overall survival (OS) with predictors. An overall response of 41.4% with a median duration of 11.9 months for stable disease and 19.5 months for complete response (CR) patients was achieved. The disease risk index (DRI) high-/very high-risk patients had a shorter OS of 4.4 months than intermediate-risk patients, with 14.5 months, = 0.007. At transplant, WT1-overexpressing patients (>150 copies) had a shorter median OS of 5.3 months than low-WT1-expressing ones, with 13.5 months, = 0.024. Furthermore, patients with ≤1000 WT1 copies at relapse had a significantly longer OS with 15.3 months than patients overexpressing WT1, with 4.4 months, = 0.0002. DRI and WT1 expression associate significantly with OS after AZA/DLI. Hence, WT1 may represent an MRD marker, especially in CR patients at high risk.
急性髓系白血病和骨髓增生异常综合征移植后复发面临有效的挽救方案受限的问题。我们回顾性分析了阿扎胞苷-供体淋巴细胞输注（AZA/DLI）在此种情况下的应用。此外，收集了骨髓中威尔姆斯肿瘤基因1（WT1）表达的数据。针对各自WT1表达水平的切点确定，采用了Cox比例风险模型，这是一种基于鞅残差最低平滑图的以结果为导向的方法。最后，Cox比例风险模型研究了总生存期（OS）与预测因素之间的关联。实现了41.4%的总体缓解率，疾病稳定患者的缓解持续时间中位数为11.9个月，完全缓解（CR）患者为19.5个月。疾病风险指数（DRI）高/极高风险患者的OS为4.4个月，短于中风险患者的14.5个月，P = 0.007。移植时，WT1过表达患者（>150拷贝）的OS中位数为5.3个月，短于低WT1表达患者的13.5个月，P = 0.024。此外，复发时WT1拷贝数≤1000的患者的OS明显更长，为15.3个月，而WT1过表达患者为4.4个月，P = 0.0002。DRI和WT1表达与AZA/DLI后的OS显著相关。因此，WT1可能代表一种微小残留病标志物，尤其是在高危CR患者中。
