Meur Grégoire Le, Plesa Adriana, Larcher Marie-Virginie, Fossard Gaëlle, Barraco Fiorenza, Loron Sandrine, Balsat Marie, Ducastelle-Leprêtre Sophie, Gilis Lila, Thomas Xavier, Ghesquières Hervé, Tigaud Isabelle, Hayette Sandrine, Huet Sarah, Sujobert Pierre, Renault Myriam, Thérèse Rubio Marie, Michallet Mauricette, Labussière-Wallet Hélène, Heiblig Maël
Department of Hematology, Lyon-Sud Hospital, Hospices Civils de Lyon, Pierre Bénite, France; Université Claude Bernard, Lyon, France.
Laboratory of Cytology and Immunology, Lyon-Sud Hospital, Hospices Civils de Lyon, Pierre Bénite, France.
Transplant Cell Ther. 2023 Jan;29(1):38.e1-38.e9. doi: 10.1016/j.jtct.2022.09.003. Epub 2022 Sep 13.
Allogeneic hematopoietic stem cell transplantation (allo-HSCT) after conditioning with a sequential association of fludarabine, amsacrine, and cytosine arabinoside (FLAMSA) followed by a reduced-intensity conditioning regimen has emerged for patients with high-risk acute myeloid leukemia (AML), especially in refractory or relapsing patients. Here we aimed to address retrospectively the impact of pretransplantation minimal residual disease (MRD) by flow cytometry on the outcomes of high-risk AML patients who underwent allo-HSCT after sequential FLAMSA-busulfan (FLAMSA-Bu)-based conditioning regimens. We included 165 high-risk AML patients who underwent transplantation after FLAMSA-BU in this retrospective single-center "real life" study. All patients received in vivo T cell depletion with antithymocyte globulin (5 mg/kg). MRD detection was based on a leukemia-associated immunophenotype using the European LeukemiaNet recommendations, with a threshold of .1%. Univariate and multivariate analyses were performed using R version 4.1.1 (R Foundation for Statistical Computing, Vienna, Austria). With a median follow-up of 4.0 years post-transplantation, the median overall survival (OS) was 54.9 months. Overall, 41 patients (24.8%) relapsed post-transplantation, with a resulting cumulative incidence of relapse (CIR) of 26.7% at 2 years and 34.0% at 5 years. Detectable MRD preceding allo-HSCT and refractory status were associated with worse median OS and CIR rates compared with patients without detectable MRD; however, OS was not significantly different between pre-HSCT MRD-positive and refractory patients (median, .7 year versus 2.0 years; P = .3). Conversely, pre-HSCT MRD negativity was associated with a reduced 2-year CIR. Neither European LeukemiaNet risk stratification nor age had a significant influence on OS. In the multivariate analysis, only pre-HSCT MRD positivity and lower conditioning regimen intensity were significantly associated with a poorer OS. The cumulative incidence of extensive chronic graft-versus-host disease at 2 years was 26.15%. The estimated nonrelapse mortality (NRM) of the entire cohort at 2 years was 23.1%, with age and unrelated donor identified as risk factors for higher NRM. Our data ahow that FLAMSA-Bu conditioning did not reverse the pejorative effect of detectable pre-HSCT MRD, suggesting that such patients should be offered alternative strategies before HSCT to reach deeper remission.
对于高危急性髓系白血病（AML）患者，尤其是难治或复发患者，在使用氟达拉滨、安吖啶和阿糖胞苷（FLAMSA）序贯联合预处理后再进行减低强度预处理方案的异基因造血干细胞移植（allo-HSCT）已逐渐兴起。在此，我们旨在回顾性研究流式细胞术检测的移植前微小残留病（MRD）对接受基于FLAMSA-白消安（FLAMSA-Bu）序贯预处理方案的allo-HSCT的高危AML患者预后的影响。在这项回顾性单中心“真实世界”研究中，我们纳入了165例接受FLAMSA-Bu预处理后进行移植的高危AML患者。所有患者均接受抗胸腺细胞球蛋白（5 mg/kg）进行体内T细胞清除。MRD检测基于欧洲白血病网的建议，采用白血病相关免疫表型，阈值为0.1%。使用R 4.1.1版本（奥地利维也纳的R统计计算基金会）进行单因素和多因素分析。移植后中位随访4.0年，中位总生存期（OS）为54.9个月。总体而言，41例患者（24.8%）移植后复发，2年时累积复发率（CIR）为26.7%，5年时为34.0%。与未检测到MRD的患者相比，allo-HSCT前可检测到MRD及难治状态与较差的中位OS和CIR率相关；然而，HSCT前MRD阳性和难治患者的OS无显著差异（中位值，0.7年对2.0年；P = 0.3）。相反，HSCT前MRD阴性与2年CIR降低相关。欧洲白血病网风险分层和年龄对OS均无显著影响。在多因素分析中，只有HSCT前MRD阳性和较低的预处理方案强度与较差的OS显著相关。2年时广泛慢性移植物抗宿主病的累积发生率为26.15%。整个队列2年时估计的非复发死亡率（NRM）为23.1%，年龄和无关供体被确定为较高NRM的危险因素。我们的数据表明，FLAMSA-Bu预处理并未逆转HSCT前可检测到MRD的不良影响，提示此类患者在HSCT前应采用替代策略以达到更深的缓解。
