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