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异基因造血干细胞移植后急性白血病或骨髓增生异常综合征中晚期微小残留病的预防性低剂量白细胞介素-2 或 DLI。

Preemptive low-dose interleukin-2 or DLI for late-onset minimal residual disease in acute leukemia or myelodysplastic syndrome after allogeneic hematopoietic stem cell transplantation.

机构信息

Bone Marrow Transplantation Center, The First Affiliated Hospital, Zhejiang University School of Medicine, 79 Qingchun Road, Hangzhou, 310003, China.

Institute of Hematology, Zhejiang University, Hangzhou, China.

出版信息

Ann Hematol. 2021 Feb;100(2):517-527. doi: 10.1007/s00277-020-04326-6. Epub 2020 Oct 31.

DOI:10.1007/s00277-020-04326-6
PMID:33128124
Abstract

Minimal residual disease (MRD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) heralds high risk of relapse. Whether preemptive recombinant interleukin-2 (pre-IL2) is effective for patients with late-onset MRD (LMRD) remains unknown. We retrospectively compared the efficacy and safety of pre-IL2 (n = 30) and pre-DLI (n = 25) for LMRD in patients receiving allo-HSCT for acute leukemia or myelodysplastic syndrome. The 1-year overall survival (OS) and disease-free survival (DFS) rates were 86.7% and 78.4% (P = 0.267), 83.3% and 75.6% (P = 0.329), the cumulative incidence of grades III-IV acute graft-versus-host disease (aGVHD) at 100 days post-preemptive intervention was 3.3% and 12.0% (P = 0.226) in the pre-IL2 group and pre-DLI group, respectively. The 1-year cumulative incidence of moderate/severe chronic GVHD (cGVHD), relapse (CIR), and non-relapse mortality (NRM) were 7.7% and 27.9% (P = 0.018), 13.6% and 20.0% (P = 0.561) and 3.3% and 5.5% (P = 0.321) in the two groups, respectively. No remarkable differences in CIR, OS, and DFS between the two intervention groups were found in multivariate analysis. The GVHD-free and relapse-free survival (GRFS) were better in the pre-IL2 group than in the pre-DLI group (HR = 0.31, 95% confidence interval (CI), 0.12-0.76; P = 0.011). In conclusion, preemptive low-dose IL2 and preemptive DLI yield comparable outcomes for patients with LMRD receiving allo-HSCT, in terms of aGVHD, NRM, relapse, OS, and DFS. However, preemptive low-dose IL2 has a lower incidence of moderate/severe cGVHD and a higher CRFS. Preemptive low-dose IL2 may be an alternative method for patients who develop LMRD after allo-HSCT, particularly for patients who cannot receive preemptive DLI.

摘要

异基因造血干细胞移植(allo-HSCT)后微小残留病(MRD)预示着复发风险高。对于发生迟发性 MRD(LMRD)的患者,预防性重组白细胞介素 2(pre-IL2)是否有效尚不清楚。我们回顾性比较了 allo-HSCT 治疗急性白血病或骨髓增生异常综合征患者中接受 LMRD 的患者使用 pre-IL2(n=30)和 pre-DLI(n=25)的疗效和安全性。1 年总生存率(OS)和无病生存率(DFS)分别为 86.7%和 78.4%(P=0.267),83.3%和 75.6%(P=0.329),在抢先干预后 100 天,预防性干预后 3.3%和 12.0%(P=0.226)的患者发生 III-IV 级急性移植物抗宿主病(aGVHD)的累积发生率在 pre-IL2 组和 pre-DLI 组中分别为 3.3%和 12.0%(P=0.226)。1 年累积中重度慢性移植物抗宿主病(cGVHD)、复发(CIR)和非复发死亡率(NRM)发生率分别为 7.7%和 27.9%(P=0.018),13.6%和 20.0%(P=0.561)和 3.3%和 5.5%(P=0.321)。多因素分析显示,两组之间 CIR、OS 和 DFS 无显著差异。与 pre-DLI 组相比,pre-IL2 组的 GVHD 无复发生存率(GRFS)和无复发生存率(DFS)更好(HR=0.31,95%置信区间(CI),0.12-0.76;P=0.011)。总之,对于接受 allo-HSCT 的 LMRD 患者,预防性低剂量 IL2 和预防性 DLI 在 aGVHD、NRM、复发、OS 和 DFS 方面的疗效相当。然而,预防性低剂量 IL2 的中重度 cGVHD 发生率较低,CRFS 较高。对于 allo-HSCT 后发生 LMRD 的患者,预防性低剂量 IL2 可能是一种替代方法,特别是对于不能接受预防性 DLI 的患者。

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