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在极高危急性髓系白血病患者中,比较亲缘单倍体与同胞相合供者 PBSCT 后预防性供者淋巴细胞输注的安全性和有效性。

Comparison of the safety and efficacy of prophylactic donor lymphocyte infusion after haploidentical versus matched-sibling PBSCT in very high-risk acute myeloid leukemia.

机构信息

Department of Hematology, Chinese PLA General Hospital, Medical School of Chinese PLA, 28 Fuxing Road, Beijing, 100853, China.

Institute of Basic Medicine, Chinese PLA General Hospital, Medical School of Chinese PLA, 28 Fuxing Road, Beijing, 100853, China.

出版信息

Ann Hematol. 2019 May;98(5):1267-1277. doi: 10.1007/s00277-019-03636-8. Epub 2019 Feb 12.

Abstract

Donor lymphocyte infusion (DLI) might be used prophylactically to reduce relapse after allogeneic hematopoietic stem cell transplantation for very high-risk leukemia/lymphoma without effective targeted therapy. To compare the safety and efficacy of prophylactic DLI for prevention of relapse after allogeneic peripheral blood stem cell transplantation from haploidentical donors (HID-SCT) and matched-sibling donors (MSD-SCT) in patients with very high-risk acute myeloid leukemia (AML), we performed a retrospective analysis in a cohort of 21 HID-SCT and 13 MSD-SCT recipients, displaying similar baseline characteristics except for donor's gender distribution. Grade 2-4 acute graft-versus-host disease (GVHD) at 100-day post-DLI was higher in HID-SCT group than that in MSD-SCT group (59.5% vs. 30.8%, p = 0.05). The grade 3-4 acute GVHD (17.5% vs. 7.7%), 1-year chronic GVHD (36.6% vs. 33.2%), and severe chronic GVHD (15.3% vs. 27.3%) were not statistically significant different between groups. One-year non-relapse mortality was higher in HID-SCT group than that in MSD-SCT group with marginal significance (27.9% vs. 0.0%, p = 0.061). One-year relapse rate was not statistically significant different between HID-SCT group and MSD-SCT group (21.6% vs. 36.5%, p = 0.543). For HID-SCT recipients, 1-year relapse rate was lower in patients receiving prophylactic DLI than that in a control cohort of eight patients with same very high-risk features but not receiving prophylactic DLI (62.5% vs. 28.3%, p = 0.037). No statistically significant difference was observed in 1-year overall survival (OS, 55.1% vs. 83.9%, p = 0.325) and relapse-free survival (RFS, 50.1% vs. 74.0%, p = 0.419) rates between HID-SCT group and MSD-SCT group. In multivariate analyses, non-remission status prior to transplant, poor-risk gene mutations, and donor's age ≥ 48 years predicted a higher risk of relapse after DLI. Non-remission status prior to transplant predicted inferior OS and RFS. Patient's age ≥ 40 years also predicted an inferior OS. In conclusion, prophylactic DLI was very safe and efficient for reducing relapse in patients with very high-risk AML receiving MSD-SCT. In the recipients of HID-SCT, the application of prophylactic DLI could reduce the risk of relapse, although with a higher incidence of DLI-associated acute GVHD than those of MSD-SCT.

摘要

供者淋巴细胞输注(DLI)可用于预防异基因造血干细胞移植后高危白血病/淋巴瘤的复发,而无有效靶向治疗。为了比较预防 DLI 在预防高危急性髓系白血病(AML)患者同种异体外周血造血干细胞移植(HID-SCT)和匹配同胞供体(MSD-SCT)后复发的安全性和有效性,我们对 21 例 HID-SCT 和 13 例 MSD-SCT 受者进行了回顾性分析,除供者性别分布外,两组具有相似的基线特征。HID-SCT 组与 MSD-SCT 组相比,100 天 DLI 后 2-4 级急性移植物抗宿主病(GVHD)发生率较高(59.5% vs. 30.8%,p=0.05)。3-4 级急性 GVHD(17.5% vs. 7.7%)、1 年慢性 GVHD(36.6% vs. 33.2%)和严重慢性 GVHD(15.3% vs. 27.3%)无统计学差异。HID-SCT 组 1 年非复发死亡率高于 MSD-SCT 组,具有显著意义(27.9% vs. 0.0%,p=0.061)。HID-SCT 组和 MSD-SCT 组 1 年复发率无统计学差异(21.6% vs. 36.5%,p=0.543)。对于 HID-SCT 受者,接受预防性 DLI 的患者 1 年复发率低于未接受预防性 DLI 的 8 例具有相同高危特征的对照组患者(62.5% vs. 28.3%,p=0.037)。HID-SCT 组和 MSD-SCT 组 1 年总生存率(OS,55.1% vs. 83.9%,p=0.325)和无复发生存率(RFS,50.1% vs. 74.0%,p=0.419)无统计学差异。移植前未缓解状态、高危基因突变和供者年龄≥48 岁是 DLI 后复发风险较高的预测因素。移植前未缓解状态预测 OS 和 RFS 预后不良。患者年龄≥40 岁也预测 OS 预后不良。总之,预防性 DLI 对预防高危 AML 患者接受 MSD-SCT 后复发非常安全有效。在 HID-SCT 受者中,预防性 DLI 的应用可以降低复发风险,尽管与 MSD-SCT 相比,DLI 相关的急性 GVHD 发生率更高。

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