Service d'Hématologie Clinique et de Thérapie Cellulaire, Hôpital Saint Antoine, APHP, 184 rue du faubourg Saint-Antoine, 75571, Paris, Cedex 12, France.
Acute Leukemia Working Party Office, Hôpital Saint Antoine, APHP, Paris, France.
J Hematol Oncol. 2017 Jun 24;10(1):130. doi: 10.1186/s13045-017-0498-8.
Primary refractory acute myeloid leukemia (PRF-AML) is associated with a dismal prognosis. Allogeneic stem cell transplantation (HSCT) in active disease is an alternative therapeutic strategy. The increased availability of unrelated donors together with the significant reduction in transplant-related mortality in recent years have opened the possibility for transplantation to a larger number of patients with PRF-AML. Moreover, transplant from unrelated donors may be associated with stronger graft-mediated anti-leukemic effect in comparison to transplantations from HLA-matched sibling donor, which may be of importance in the setting of PRF-AML.
The current study aimed to address the issue of HSCT for PRF-AML and to compare the outcomes of HSCT from matched sibling donors (n = 660) versus unrelated donors (n = 381), for patients with PRF-AML between 2000 and 2013. The Kaplan-Meier estimator, the cumulative incidence function, and Cox proportional hazards regression models were used where appropriate.
HSCT provide patients with PRF-AML a 2-year leukemia-free survival and overall survival of about 25 and 30%, respectively. In multivariate analysis, two predictive factors, cytogenetics and time from diagnosis to transplant, were associated with lower leukemia-free survival, whereas Karnofsky performance status at transplant ≥90% was associated with better leukemia-free survival (LFS). Concerning relapse incidence, cytogenetics and time from diagnosis to transplant were associated with increased relapse. Reduced intensity conditioning regimen was the only factor associated with lower non-relapse mortality.
HSCT was able to rescue about one quarter of the patients with PRF-AML. The donor type did not have any impact on PRF patients' outcomes. In contrast, time to transplant was a major prognostic factor for LFS. For patients with PRF-AML who do not have a matched sibling donor, HSCT from an unrelated donor is a suitable option, and therefore, initiation of an early search for allocating a suitable donor is indicated.
原发性难治性急性髓系白血病（PRF-AML）预后不良。在疾病活动期进行异基因造血干细胞移植（HSCT）是一种替代治疗策略。近年来，无关供者的可用性增加以及移植相关死亡率的显著降低，为更多 PRF-AML 患者进行移植创造了可能。此外，与 HLA 匹配的同胞供者相比，无关供者的移植可能与更强的移植物介导的抗白血病效应相关，这在 PRF-AML 中可能很重要。
本研究旨在解决 PRF-AML 的 HSCT 问题，并比较 2000 年至 2013 年间 PRF-AML 患者接受同胞供者（n=660）与无关供者（n=381）HSCT 的结果。使用 Kaplan-Meier 估计器、累积发生率函数和 Cox 比例风险回归模型进行适当分析。
HSCT 可为 PRF-AML 患者提供约 25%和 30%的 2 年无白血病生存率和总生存率。多变量分析显示，细胞遗传学和诊断至移植时间是与无白血病生存率降低相关的两个预测因素，而移植时 Karnofsky 表现状态≥90%与无白血病生存率改善相关。关于复发发生率，细胞遗传学和诊断至移植时间与复发增加相关。降低强度的预处理方案是唯一与较低的非复发死亡率相关的因素。
HSCT 能够挽救约四分之一的 PRF-AML 患者。供者类型对 PRF 患者的结果没有影响。相反，移植时间是无白血病生存率的主要预后因素。对于没有匹配同胞供者的 PRF-AML 患者，无关供者的 HSCT 是一种合适的选择，因此，应尽早开始寻找合适的供者。
