Donor lymphocyte infusion for prevention of relapse after unmanipulated haploidentical PBSCT for very high-risk hematologic malignancies.
Donor lymphocyte infusion for prevention of relapse after unmanipulated haploidentical PBSCT for very high-risk hematologic malignancies.
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供体淋巴细胞输注用于预防极高危血液恶性肿瘤未经操作的半相合 PBSCT 后复发
DOI：
10.1007/s00277-018-3482-7
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发表时间：
2019-01
影响因子：
3.5
通讯作者：
Liu DH
中科院分区：
文献类型：
--
作者：
Gao XN;Lin J;Wang SH;Huang WR;Li F;Li HH;Chen J;Wang LJ;Gao CJ;Yu L;Liu DH
未经处理的单倍体相合外周血干细胞移植(Haplo-PBSCT)已成为治疗高危白血病/淋巴瘤的公认疗法。复发是复发/难治性疾病或具有非常高风险的基因突变(如TP53、TET2和DNMT3a)的患者治疗失败的主要原因。在这项研究中，我们旨在建立预防性供者淋巴细胞输注(DLI)与G-CSF启动的外周血祖细胞输注(DLI)的耐受性和有效性，以防止这些高危患者在单核/单核细胞移植后复发。在连续45例极高风险白血病/淋巴瘤患者中，31例在移植后中位数77天给予预防性DLI。Cd~(3+)细胞输注中位数为1.8 × ~(107)/kg。DLI后100天急性移植物抗宿主病(GVHD)2~4级和3~4级的发生率分别为55.3%和10.2%。慢性移植物抗宿主病和重度慢性移植物抗宿主病的2年发生率分别为52.0%和18.2%。2年无复发死亡率和复发率分别为33.1%和32.5%。2年总生存率和无复发生存率分别为40.1%和31.9%。低风险基因突变(p= 0.029)、移植前未缓解状态的疾病(p= 0.005)、40岁以上的供者(p= 0.043)与移植后复发有关。在多变量分析中，移植前处于未缓解状态的疾病是复发的独立危险因素(危险比 = 为4.079；p= 0.035)。这些数据表明预防性DLI在单核-外周血干细胞移植环境中的可行性以及在极高风险白血病/淋巴瘤中的抗白血病效果。
Unmanipulated haploidentical peripheral blood stem cell transplantation (haplo-PBSCT) has been an established treatment to cure high-risk leukemia/lymphoma. Relapse is the main cause of treatment failure for patients with relapsed/refractory disease or with very high-risk gene mutations such asTP53,TET2, andDNMT3a. In this study, we aimed to establish the tolerance and efficacy of prophylactic donor lymphocyte infusion (DLI) with G-CSF-primed peripheral blood progenitors for prevention of relapse in these very high-risk patients after haplo-PBSCT. The prophylactic DLI was given at a median of 77 days after transplantation in 31 of 45 consecutive patients with very high-risk leukemia/lymphoma. The median dose of CD3+cells for infusion was 1.8 × 107/kg. The 100-day incidences of acute graft-versus-host disease (GVHD) grades 2–4 and 3–4 after DLI were 55.3% and 10.2%. The 2-year incidences of chronic GVHD and severe chronic GVHD were 52.0% and 18.2%. The 2-year incidences of non-relapse mortality and relapse were 33.1% and 32.5%. The 2-year probabilities of overall survival and relapse-free survival were 40.1% and 31.9%. Poor-risk gene mutations (p= 0.029), disease in non-remission status prior to transplantation (p= 0.005), and donors older than 40 years of age (p= 0.043) were associated with relapse after DLI. In multivariate analysis, disease in non-remission status prior to transplantation was an independent risk factor of relapse (hazard ratio = 4.079;p= 0.035). These data showed the feasibility of the prophylactic DLI in the haplo-PBSCT setting and the anti-leukemic efficacy in very high-risk leukemia/lymphoma.
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影响因子：
45.3
作者：
Schlenk, Richard F.;Doehner, Konstanze;Doelmer, Hartmut
通讯作者：
Doelmer, Hartmut
影响因子：
6.5
作者：
Middeke, Jan M.;Herold, Sylvia;Schetelig, Johannes
通讯作者：
Schetelig, Johannes
影响因子：
4.8
作者：
Locke, F.;Agarwal, R.;Kunnavakkam, R.;van Besien, K.;Larson, R. A.;Odenike, O.;Godley, L. A.;Liu, H.;Le Beau, M. M.;Gurbuxani, S.;Thirman, M. J.;Sipkins, D.;White, C.;Artz, A.;Stock, W.
通讯作者：
Stock, W.
晚期急性白血病患者在 HLA 不匹配/半相合、T 细胞充足的造血 SCT 后使用粒细胞 CSF 引发的 PBPC 预防复发：回顾性危险因素分析
影响因子：
4.8
作者：
Wang, Y.;Liu, D-H;Huang, X-J
通讯作者：
Huang, X-J
影响因子：
4.3
作者：
Liga, Maria;Triantafyllou, Evangelia;Spyridonidis, Alexandros
通讯作者：
Spyridonidis, Alexandros