Rubio Marie Thérèse, D'Aveni-Piney Maud, Labopin Myriam, Hamladji Rose-Marie, Sanz Miguel A, Blaise Didier, Ozdogu Hakan, Daguindeau Etienne, Richard Carlos, Santarone Stella, Irrera Giuseppe, Yakoub-Agha Ibrahim, Yeshurun Moshe, Diez-Martin Jose L, Mohty Mohamad, Savani Bipin N, Nagler Arnon
Service d'Hématologie et de Médecine interne, Hôpital Brabois, CHRU Nancy, Nancy, France.
IMoPA, CNRS UMR 7365, Nancy, France.
J Hematol Oncol. 2017 Jan 24;10(1):31. doi: 10.1186/s13045-016-0389-4.
The impact of the use of anti-thymocyte globulin (ATG) in allogeneic stem cell transplantation performed with HLA-identical sibling donors following fludarabine and 4 days intravenous busulfan myeloablative conditioning regimen has been poorly explored.
We retrospectively analyzed 566 patients who underwent a first HLA-identical allogeneic stem cell transplantation with this conditioning regimen for acute myeloid leukemia in first complete remission between 2006 and 2013 and compared the outcomes of 145 (25.6%) patients who received ATG (ATG group) to 421 (74.4%) who did not (no-ATG group). The Kaplan-Meier estimator, the cumulative incidence function, and Cox proportional hazards regression models were used where appropriate.
Patients in the ATG group were older, received more frequently peripheral blood stem cell grafts from older donors, and were transplanted more recently. With a median follow-up of 19 months, patients in the ATG group had reduced 2-year cumulative incidence of chronic graft-versus-host disease (GVHD) (31 vs. 52%, p = 0.0002) and of its extensive form (8 vs. 26%, p < 0.0001) but similar relapse incidence (22 vs. 27%, p = 0.23) leading to improved GVHD and relapse-free survival (GRFS) (60 vs. 40%, p = 0.0001). In multivariate analyses, the addition of ATG was independently associated with lower chronic GVHD (HR = 0.46, p = 0.0001), improved leukemia-free survival (HR = 0.67, p = 0.027), overall survival (HR = 0.65, p = 0.027), and GRFS (HR = 0.51, p = 4 × 10). Recipient age above 50 years was the only other factor associated with worse survivals.
These results suggest that the use of ATG with fludarabine and 4 days intravenous busulfan followed by HLA-identical sibling donor allogeneic stem cell transplantation for acute myeloid leukemia improves overall transplant outcomes due to reduced incidence of chronic GVHD without increased relapse risk.
对于采用氟达拉滨和4天静脉注射白消安进行清髓预处理方案、由人类白细胞抗原（HLA）匹配的同胞供者进行的异基因干细胞移植，抗胸腺细胞球蛋白（ATG）的使用影响尚未得到充分研究。
我们回顾性分析了2006年至2013年间566例首次接受该预处理方案进行HLA匹配的异基因干细胞移植以治疗首次完全缓解期急性髓系白血病的患者，并将145例（25.6%）接受ATG治疗的患者（ATG组）与421例（74.4%）未接受ATG治疗的患者（非ATG组）的结局进行比较。在适当情况下使用了Kaplan-Meier估计法、累积发病率函数和Cox比例风险回归模型。
ATG组患者年龄更大，更频繁地接受来自年龄较大供者的外周血干细胞移植，且移植时间更近。中位随访19个月，ATG组患者2年慢性移植物抗宿主病（GVHD）累积发病率降低（31%对52%，p = 0.0002）及其广泛型发病率降低（8%对26%，p < 0.0001），但复发率相似（22%对27%，p = 0.23），从而导致GVHD和无复发生存率（GRFS）提高（60%对40%，p = 0.0001）。在多变量分析中，加用ATG与较低的慢性GVHD独立相关（风险比[HR]=0.46，p = 0.0001）、改善无白血病生存率（HR = 0.67，p = 0.027）、总生存率（HR = 0.65，p = 0.027）和GRFS（HR = 0.51，p = 4×10）。50岁以上的受者年龄是唯一与较差生存率相关的其他因素。
这些结果表明，对于急性髓系白血病，在氟达拉滨和4天静脉注射白消安后使用ATG，继之以HLA匹配的同胞供者异基因干细胞移植，可改善总体移植结局，因为慢性GVHD发病率降低且不增加复发风险。
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