预处理强度对T细胞充足的单倍体相合干细胞移植治疗急性白血病的影响：欧洲血液与骨髓移植协会急性白血病工作组的报告
Impact of conditioning intensity in T-replete haplo-identical stem cell transplantation for acute leukemia: a report from the acute leukemia working party of the EBMT.
作者信息
Rubio Marie T, Savani Bipin N, Labopin Myriam, Piemontese Simona, Polge Emmanuelle, Ciceri Fabio, Bacigalupo Andrea, Arcese William, Koc Yener, Beelen Dietrich, Gülbas Zafer, Wu Depei, Santarone Stella, Tischer Johanna, Afanasyev Boris, Schmid Christoph, Giebel Sebastian, Mohty Mohamad, Nagler Arnon
机构信息
Service d'Hématologie et de Thérapie cellulaire, Saint Antoine Hospital, Paris, France.
INSERM UMR 938, Paris, France.
出版信息
J Hematol Oncol. 2016 Mar 15;9:25. doi: 10.1186/s13045-016-0248-3.
BACKGROUND
Increasing numbers of patients are receiving haplo-identical stem cell transplantation (haplo-SCT) for treatment of acute leukemia with reduced intensity (RIC) or myeloablative (MAC) conditioning regimens. The impact of conditioning intensity in haplo-SCT is unknown.
METHODS
We performed a retrospective registry-based study comparing outcomes after T-replete haplo-SCT for patients with acute myeloid (AML) or lymphoid leukemia (ALL) after RIC (n = 271) and MAC (n = 425). Regimens were classified as MAC or RIC based on published criteria.
RESULTS
A combination of post-transplant cyclophosphamide (PT-Cy) with one calcineurin inhibitor and mycophenolate mofetil (PT-Cy-based regimen) for graft-versus-host disease (GVHD) prophylaxis was used in 66 (25%) patients in RIC and 125 (32%) in MAC groups. Patients of RIC group were older and had been transplanted more recently and more frequently for AML with active disease at transplant. Percentage of engraftment (90 vs. 92%; p = 0.58) and day 100 grade II to IV acute GVHD (24 vs. 29%, p = 0.23) were not different between RIC and MAC groups. Multivariable analyses, run separately in AML and ALL, showed a trend toward higher relapse incidence with RIC in comparison to MAC in AML (hazard ratio (HR) 1.34, p = 0.09), and no difference in both AML and ALL in terms of non-relapse mortality (NRM) chronic GVHD and leukemia-free survival. There was no impact of conditioning regimen intensity in overall survival (OS) in AML (HR = 0.97, p = 0.79) but a trend for worse OS with RIC in ALL (HR = 1.44, p = 0.10). The main factor impacting outcomes was disease status at transplantation (HR ≥ 1.4, p ≤ 0.01). GVHD prophylaxis with PT-Cy-based regimen was independently associated with reduced NRM (HR 0.63, p = 0.02) without impact on relapse incidence (HR 0.99, p = 0.94).
CONCLUSIONS
These data suggest that T-replete haplo-SCT with both RIC and MAC, in particular associated with PT-Cy, are valid options in first line treatment of high risk AML or ALL.
背景
越来越多的患者正在接受单倍体相合干细胞移植（haplo-SCT），用于采用减低强度（RIC）或清髓性（MAC）预处理方案治疗急性白血病。预处理强度在单倍体相合干细胞移植中的影响尚不清楚。
方法
我们进行了一项基于登记处的回顾性研究，比较了接受RIC（n = 271）和MAC（n = 425）预处理后急性髓系白血病（AML）或淋巴细胞白血病（ALL）患者进行全T细胞单倍体相合干细胞移植后的结局。根据已发表的标准将预处理方案分类为MAC或RIC。
结果
66例（25%）RIC组患者和125例（32%）MAC组患者采用了移植后环磷酰胺（PT-Cy）联合一种钙调神经磷酸酶抑制剂和霉酚酸酯（基于PT-Cy的方案）预防移植物抗宿主病（GVHD）。RIC组患者年龄较大，且最近因移植时处于活动期的AML接受移植的频率更高。RIC组和MAC组之间的植入率（90%对92%；p = 0.58）和100天II至IV级急性GVHD发生率（24%对29%，p = 0.23）无差异。在AML和ALL中分别进行的多变量分析显示，与MAC相比，RIC组AML的复发率有升高趋势（风险比（HR）1.34，p = 0.09），在AML和ALL中，非复发死亡率（NRM）、慢性GVHD和无白血病生存率方面无差异。预处理方案强度对AML的总生存期（OS）无影响（HR = 0.97，p = 0.79），但ALL中RIC组OS有变差趋势（HR = 1.44，p = 0.10）。影响结局的主要因素是移植时的疾病状态（HR≥1.4，p≤0.01）。基于PT-Cy的方案预防GVHD与降低NRM独立相关（HR 0.63，p = 0.02），对复发率无影响（HR 0.99，p = 0.94）。
结论
这些数据表明，采用RIC和MAC的全T细胞单倍体相合干细胞移植，尤其是与PT-Cy联合使用，是高危AML或ALL一线治疗的有效选择。
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