T cell-depleted partial matched unrelated donor transplant for advanced myeloid malignancy: KIR ligand mismatch and outcome.
T cell-depleted partial matched unrelated donor transplant for advanced myeloid malignancy: KIR ligand mismatch and outcome.
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用于晚期骨髓恶性肿瘤的 T 细胞耗尽部分匹配无关供体移植：KIR 配体不匹配和结果。
DOI：
10.1016/j.bbmt.2011.11.024
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发表时间：
2012
期刊：
影响因子：
--
通讯作者：
Miller,Jeffrey
中科院分区：
文献类型：
--
作者：
Weisdorf,Daniel;Cooley,Sarah;Devine,Steven;Fehniger,ToddA;DiPersio,John;Anasetti,Claudio;Waller,EdmundK;Porter,David;Farag,Sherif;Drobyski,William;Defor,Todd;Haagenson,Michael;Curtsinger,Julie;Miller,Jeffrey
为了评估高剂量预处理、CD 34选择和增强的自然杀伤（NK）细胞同种异体反应性在单倍体相合移植后的适用性，我们对缺乏相关或匹配良好的非相关供体（URD）的晚期/高危髓性白血病患者进行了相同的策略测试。在一项前瞻性多中心临床试验中，使用移植前预处理塞替派（5 mg/kg/天× 2）、氟达拉滨（40 mg/mg/M2/天× 5）和全身放疗（800 cGy）加胸腺球蛋白（2.5 mg/kg/天× 2），以及CD 34选择性非格司亭刺激的部分匹配URD外周血移植物，我们治疗了24例患者。患者（中位年龄40岁[范围：22-61岁]）与其供体在10个HLA位点中的1-3个位点上不匹配;所有患者在HLA-C位点上都不匹配。37%是少数民族或种族。24例中有21例迅速植入，1例原发性移植失败，2例早期死亡。II-IV级急性移植物抗宿主病（aGVHD）（34%，95%置信区间[CI]，14-54%）、慢性GVHD（20%，95% CI，2%-38%）和复发（26%，95% CI，8%-84%）的累积发生率不受KIR配体供体：受体错配（n = 5）与KIR配体匹配（n = 19）的影响。仅3例（12%）发生III-IV级GVHD。100天时无复发率为17%（95% CI，30%-31%），1年时为35%（95% CI，15%-55%）。两年生存率和无白血病生存率均为40%（95%CI，21%-59%），在KIR配体匹配或不匹配的患者中相似。感染，主要是在前2个月，是频繁的，并在5例患者（35%的死亡）的死亡原因。T细胞恢复和NK细胞增殖和功能成熟不受KIR配体匹配或错配状态的影响。对于这些高风险患者，这种高强度方案和T耗竭方法产生了令人满意的结局，但在为高风险、不稳定白血病患者安排URD移植物方面的后勤困难限制了增加。仍然需要改善移植围术期疾病控制和增加异基因移植物抗白血病效应的额外措施。
To evaluate the applicability of high-dose conditioning, CD34 selection, and enhanced natural killer (NK) cell alloreactivity reported as promising after haploidentical transplantation, we tested the same strategy for patients with advanced/high-risk myeloid leukemia lacking either related or well-matched unrelated donors (URD). In a prospective multicenter clinical trial using pretransplantation conditioning of thiotepa (5 mg/kg/day × 2), fludarabine (40 mg/mg/M2/day × 5), and total body radiation (800 cGy) plus thymoglobulin (2.5 mg/kg/day × 2), as well as a CD34 selected filgrastim stimulated peripheral blood graft from a partial matched URD, we treated 24 patients. The patients (median age 40 [range: 22-61]) were mismatched at 1-3 of 10 HLA loci with their donors; all were mismatched at HLA-C. Thirty-seven percent were ethnic or racial minorities. Twenty-one of 24 engrafted promptly with 1 primary graft failure and 2 early deaths. The cumulative incidence of grade II-IV acute graft-versus-host disease (aGVHD) (34%, 95% confidence interval [CI], 14-54%), chronic GVHD (20%, 95% CI, 2%-38%), and relapse (26%, 95% CI, 8%-84%) were unaffected by KIR ligand donor:recipient mismatch (n = 5) versus KIR ligand match (n = 19). Only 3 (12%) had grade III-IV GVHD. Nonrelapse occurred in 17% (95% CI, 30%-31%) by 100 days and in 35% (95% CI, 15%-55%) by 1 year. Two-year survival and leukemia-free survival were each 40% (95% CI, 21%-59%) and was similar in KIR ligand matched or mismatched patients. Infections, mostly in the first 2 months, were frequent, and were the cause of death in 5 patients (35% of deaths). T cell recovery and NK cell proliferation and functional maturation were not altered by KIR ligand match or mismatch status. For these high-risk patients, this high intensity regimen and T depleted approach yielded satisfactory outcomes, but logistical difficulties in arranging URD grafts for patients with high-risk, unstable leukemia limited accrual. Improvements in peritransplantation disease control and additional measures to augment the allogeneic graft-versus-leukemia effect are still required.
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影响因子：
4.3
作者：
Woolfrey, Ann;Klein, John P.;Haagenson, Michael;Spellman, Stephen;Petersdorf, Effie;Oudshoorn, Machteld;Gajewski, James;Hale, Gregory A.;Horan, John;Battiwalla, Minoo;Marino, Susana R.;Setterholm, Michelle;Ringden, Olle;Hurley, Carolyn;Flomenberg, Neal;Anasetti, Claudio;Fernandez-Vina, Marcelo;Lee, Stephanie J.
通讯作者：
Lee, Stephanie J.
影响因子：
20.3
作者：
Cooley, S;McCullar, V;Miller, JS
通讯作者：
Miller, JS
成人急性髓系白血病同种异体造血细胞移植：神话、争议和未知 (Blood (2011) 117, 8 (2307-2318))
DOI：
--
发表时间：
2012
期刊：
影响因子：
--
作者：
Vikas Gupta;M. Tallman;D. Weisdorf
通讯作者：
D. Weisdorf
影响因子：
20.3
作者：
Miller, Jeffery S.;Cooley, Sarah;Weisdorf, Daniel J.
通讯作者：
Weisdorf, Daniel J.
影响因子：
20.3
作者：
Brunstein, Claudio G.;Fuchs, Ephraim J.;O'Donnell, Paul V.
通讯作者：
O'Donnell, Paul V.