Sockel Katja, Stölzel Friedrich, Hönl Franziska, Baldauf Henning, Röllig Christoph, Wermke Martin, von Bonin Malte, Teipel Raphael, Link-Rachner Cornelia, Brandt Kalina, Kroschinsky Frank, Hänel Mathias, Morgner Anke, Klesse Christian, Ehninger Gerhard, Platzbecker Uwe, Bornhäuser Martin, Schetelig Johannes, Middeke Jan Moritz
Medical Clinic and Policlinic I, University Hospital Carl Gustav Carus and Medical Faculty of the TU Dresden, Dresden, Germany.
Clinical Trials Unit, DKMS, Dresden, Germany.
Cancer Manag Res. 2022 Feb 15;14:547-559. doi: 10.2147/CMAR.S339846. eCollection 2022.
Allogeneic hematopoietic cell transplantation (HCT) during chemotherapy-induced aplasia may offer long-term survival in acute myeloid leukemia (AML) with otherwise poor prognosis including ELN adverse risk, relapsed or refractory disease. However, the value of residual morphologic disease prior HCT in this context has not been conclusively settled until yet. Therefore, we aimed to investigate variables predicting outcome in this unique setting of sequential conditioning therapy, with a focus on pretreatment morphologic blast count. In contrast to the most popular FLAMSA-RIC protocol, we used a melphalan-based conditioning regimen during aplasia.
We retrospectively analyzed data from 173 AML patients who underwent a sequential melphalan-based conditioning therapy between 2003 and 2015 at our centre. All patients participated either in the prospective Phase 2 BRIDGE trial (NCT01295307), the Phase 3 AML2003 study (NCT00180102) or were treated according to this protocol and underwent allogeneic HCT after melphalan-based conditioning in treatment-induced aplasia.
Median bone marrow blast count prior to conditioning was 10% (range, 0-96%). Four year probabilities of EFS and OS were 34% (95% CI, 28-43%) and 43% (95% CI, 36-52%), respectively. In multivariate analysis, blast count >20% was associated with worse EFS (HR = 1.93; = 0.009) and OS (HR = 1.80; = 0.026). This effect was not significant anymore for HCT during 1st line therapy.
Allogeneic HCT in aplasia with a melphalan-based conditioning regimen has the potential to cure a subset of adverse risk AML patients, even with persistent morphological disease prior HCT. However, a high pre-transplant blast count still indicates patients with a dismal prognosis, especially in the relapsed patient group, for whom post-transplant strategies should be considered to further optimize post HCT outcome.
化疗诱导再生障碍期间进行异基因造血细胞移植（HCT）可能使急性髓系白血病（AML）患者获得长期生存，这些患者预后原本较差，包括欧洲白血病网络（ELN）不良风险、复发或难治性疾病。然而，在此背景下，HCT前残留形态学疾病的价值尚未最终确定。因此，我们旨在研究在这种独特的序贯预处理治疗环境中预测结局的变量，重点关注预处理时的形态学原始细胞计数。与最常用的氟达拉滨-减低强度预处理（FLAMSA-RIC）方案不同，我们在再生障碍期间使用了基于美法仑的预处理方案。
我们回顾性分析了2003年至2015年间在我们中心接受基于美法仑的序贯预处理治疗的173例AML患者的数据。所有患者均参与了前瞻性2期BRIDGE试验（NCT01295307）、3期AML2003研究（NCT00180102），或按照该方案接受治疗，并在基于美法仑的预处理诱导治疗再生障碍后接受异基因HCT。
预处理前骨髓原始细胞计数中位数为10%（范围0-96%）。无事件生存期（EFS）和总生存期（OS）的4年概率分别为34%（95%置信区间，28-43%）和43%（95%置信区间，36-52%）。多变量分析中，原始细胞计数>20%与较差的EFS（风险比[HR]=1.93；P=0.009）和OS（HR=1.80；P=0.026）相关。对于一线治疗期间的HCT，这种影响不再显著。
采用基于美法仑的预处理方案在再生障碍期进行异基因HCT有可能治愈一部分不良风险AML患者，即使HCT前存在持续性形态学疾病。然而，移植前原始细胞计数高仍表明患者预后不佳，尤其是在复发患者组中，对此应考虑移植后策略以进一步优化HCT后的结局。
