Winters Amanda C, Bosma Grace, Abbott Diana, Minhajuddin Mohd, Jordan Craig, Pollyea Daniel A, Gutman Jonathan A
Center for Cancer & Blood Disorders, Department of Pediatrics, University of Colorado, Aurora, Colorado.
Center for Innovative Design & Analysis, University of Colorado, Aurora, Colorado.
Transplant Cell Ther. 2022 Oct;28(10):694.e1-694.e9. doi: 10.1016/j.jtct.2022.07.022. Epub 2022 Jul 25.
Allogeneic hematopoietic stem cell transplantation (SCT) after a patient with acute myeloid leukemia (AML) achieves a remission from intensive chemotherapy (IC) is given with curative intent. Recently, venetoclax-based regimens have become the standard of care for patients with newly diagnosed AML who are unfit for IC. If these patients achieve remission, they may also be considered for potentially curative consolidation with SCT. There are limited data comparing outcomes after SCT with these different induction strategies. The purpose of the current study was to evaluate depth of remission before SCT and outcomes after SCT in adults with nonrelapsed/refractory AML receiving pre-SCT therapy with either venetoclax/azacitidine (ven/aza) or IC. This was a retrospective, single-institution analysis of 169 patients receiving SCT in first remission after IC or ven/aza. Patient demographics and AML risk features were collected, as well as pre-SCT measurable residual disease (MRD) assessed by flow cytometry and molecular methods. Relapse, transplantation-related mortality, incidence of acute and chronic graft-versus-host-disease (GVHD), and death from any cause were also recorded. Descriptive and survival statistics were applied to these data to compare IC and ven/aza groups. Cox proportional hazard models were used for univariate and multivariate analyses. We demonstrate that despite differences in baseline factors between these groups, outcomes were similar. Relapse-free and overall survival, as well as cumulative incidences of transplantation-related mortality, relapse, and acute and chronic GVHD were comparable between groups. Exploring survival in younger (<65 years) versus older (≥65 years) patients by treatment group did not alter these results. Finally, although pre-SCT MRD by flow cytometry was significantly predictive of post-SCT relapse and survival in the IC + SCT patients, it was not significantly predictive of relapse and survival in the ven/aza + SCT patients. Although these findings require prospective validation in a larger cohort of patients, they suggest that ven/aza followed by SCT is a reasonable management strategy for transplantation candidates at any age.
急性髓系白血病（AML）患者在强化化疗（IC）后达到缓解后进行异基因造血干细胞移植（SCT）旨在治愈。最近，基于维奈克拉的方案已成为不适合IC的新诊断AML患者的标准治疗方法。如果这些患者达到缓解，也可考虑进行可能治愈性的SCT巩固治疗。比较这些不同诱导策略后SCT结果的数据有限。本研究旨在评估接受维奈克拉/阿扎胞苷（ven/aza）或IC进行SCT前治疗的非复发/难治性AML成人患者SCT前的缓解深度和SCT后的结果。这是一项对169例在IC或ven/aza后首次缓解时接受SCT的患者进行的回顾性单机构分析。收集了患者的人口统计学和AML风险特征，以及通过流式细胞术和分子方法评估的SCT前可测量残留病（MRD）。还记录了复发、移植相关死亡率、急性和慢性移植物抗宿主病（GVHD）的发生率以及任何原因导致的死亡。对这些数据应用描述性和生存统计来比较IC组和ven/aza组。使用Cox比例风险模型进行单变量和多变量分析。我们证明，尽管这些组之间的基线因素存在差异，但结果相似。两组之间的无复发生存率和总生存率，以及移植相关死亡率、复发率以及急性和慢性GVHD的累积发生率相当。按治疗组探索年轻（<65岁）与年长（≥65岁）患者的生存情况并未改变这些结果。最后，尽管流式细胞术检测的SCT前MRD在IC + SCT患者中对SCT后复发和生存有显著预测作用，但在ven/aza + SCT患者中对复发和生存并无显著预测作用。尽管这些发现需要在更大的患者队列中进行前瞻性验证，但它们表明ven/aza后进行SCT是任何年龄移植候选者的合理管理策略。
