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A Phase 2 Trial of KIR-Mismatched Unrelated Donor Transplantation Using in Vivo T Cell Depletion with Antithymocyte Globulin in Acute Myelogenous Leukemia: Children's Oncology Group AAML05P1 Study.
Biology of Blood and Marrow Transplantation ( IF 5.609 ) Pub Date : 2019-12-21 , DOI: 10.1016/j.bbmt.2019.12.723
Stella M Davies 1 , Robert Iannone 2 , Todd A Alonzo 3 , Yi-Cheng Wang 4 , Robert Gerbing 4 , Sandeep Soni 5 , E Anders Kolb 6 , Soheil Meshinchi 7 , Paul J Orchard 8 , Linda J Burns 9 , Shalini Shenoy 10 , Wing Leung 11
Affiliation  

Patients with acute myelogenous leukemia (AML) who undergo killer immunoglobulin-like receptor (KIR)-mismatched haploidentical hematopoietic stem cell transplantation (HSCT) have improved survival. Children's Oncology Group AAML05P1 is a prospective phase 2 trial of unrelated donor (URD) HSCT in which KIR typing of donors was available to the treating physician at donor selection, aiming to determine feasibility (defined as the ability to obtain donor samples from URDs and obtain KIR data before transplantation) of prospective selection of KIR-mismatched donors and effect on outcomes. Patients age ≤30 years with high-risk AML at presentation or relapsed AML were eligible; the study accrued 90 evaluable patients. After enrollment, as many as 5 potential URD samples were KIR-typed (including gene expression) in a central laboratory and results reported to the treating physician, who made the final donor selection. Cases were categorized as KIR-matched or KIR-mismatched using different published strategies. Overall survival (OS), disease-free survival (DFS), and relapse did not differ significantly by KIR mismatch status. Acute graft-versus-host disease (GVHD) was significantly lower in recipients of KIR-mismatched stem cells (35% versus 60%; P = .027). We examined DFS according to time to natural killer (NK) receptor recovery after HSCT. NK p44 recovery was significantly associated with KIR mismatch and with decreased DFS and increased relapse risk in multivariate Cox analysis (P = .006 and .009, respectively). We show that prospective selection of URD according to KIR type was feasible, acute GVHD was reduced, but survival did not differ using any model of KIR mismatch. However, the study enrolled mostly matched transplants, so ligand-ligand mismatch was rare, and thus the sample size was insufficient to determine potential benefit according to this model. Cord blood recipients demonstrated a trend toward improved DFS with KIR mismatch, but the study was not powered to detect a difference in this small subset of patients. Our data suggest that recovery of NK receptor expression might influence DFS after HSCT.

中文翻译:

在急性骨髓性白血病中使用抗胸腺细胞球蛋白的体内T细胞耗竭进行的KIR不匹配不相关供体移植的2期试验:儿童肿瘤学组AAML05P1研究。

经历了致命性免疫球蛋白样受体(KIR)错配的单倍型造血干细胞移植(HSCT)的急性骨髓性白血病(AML)患者的生存期得到了改善。儿童肿瘤学组AAML05P1是一项不相关捐赠者(URD)HSCT的前瞻性2期试验,其中供主治医师在选择捐赠者时可以使用捐赠者的KIR分型,目的是确定可行性(定义为从URD获取捐赠者样本并获得捐赠者的能力。移植前的KIR数据)前瞻性选择KIR不匹配的供体及其对结局的影响。符合条件的年龄≤30岁的高危AML或复发性AML患者符合条件;该研究招募了90名可评估的患者。报名之后 在一个中央实验室中,对多达5个潜在的URD样本进行了KIR分型(包括基因表达),并将结果报告给了治疗医师,由该医师最终选择了供体。使用不同的已发布策略将病例分类为KIR匹配或KIR不匹配。KIR不匹配状态的总生存期(OS),无病生存期(DFS)和复发率没有显着差异。在KIR不匹配的干细胞接受者中,急性移植物抗宿主病(GVHD)显着降低(35%比60%; P = .027)。我们根据HSCT后恢复自然杀伤(NK)受体的时间检查了DFS。在多变量Cox分析中,NK p44的恢复与KIR失配,DFS降低和复发风险显着相关(分别为P = 0.006和.009)。我们表明,根据KIR类型对URD进行前瞻性选择是可行的,急性GVHD降低了,但使用任何KIR不匹配模型均未改变生存率。但是,该研究招募了大多数匹配的移植物,因此配体-配体错配很少见,因此样本量不足以确定该模型的潜在益处。脐带血接受者显示出KIR不匹配时DFS改善的趋势,但该研究未能发现这一小部分患者的差异。我们的数据表明,HSCT后NK受体表达的恢复可能会影响DFS。因此样本数量不足以根据此模型确定潜在收益。脐带血接受者显示出KIR不匹配时DFS改善的趋势,但该研究未能发现这一小部分患者的差异。我们的数据表明,HSCT后NK受体表达的恢复可能会影响DFS。因此样本数量不足以根据此模型确定潜在收益。脐带血接受者显示出KIR不匹配时DFS改善的趋势,但该研究未能发现这一小部分患者的差异。我们的数据表明,HSCT后NK受体表达的恢复可能会影响DFS。
更新日期:2019-12-21
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