Use of matched unrelated donors compared with matched related donors is associated with lower relapse and superior progression-free survival after reduced-intensity conditioning hematopoietic stem cell transplantation.
Use of matched unrelated donors compared with matched related donors is associated with lower relapse and superior progression-free survival after reduced-intensity conditioning hematopoietic stem cell transplantation.
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DOI：
10.1016/j.bbmt.2010.12.702
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发表时间：
2011-08
影响因子：
4.3
通讯作者：
Alyea, Edwin P.
中科院分区：
文献类型：
--
作者：
Ho, Vincent T.;Kim, Haesook T.;Aldridge, Julie;Liney, Deborah;Kao, Grace;Armand, Philippe;Koreth, John;Cutler, Corey;Ritz, Jerome;Antin, Joseph H.;Soiffer, Robert J.;Alyea, Edwin P.
由于低强度预处理（RIC）造血干细胞移植（HSCT）的成功主要依赖于移植物抗白血病（GVL）活性，与相关供体相比，无关供体中HLA差异增加可能对移植结果产生显著影响。为了评估与匹配的相关供体（MRD）相比，使用无关供体（URD）是否在RIC HSCT中产生更有效的GVL，我们回顾性研究了本机构433例连续T-完全6/6 HLA匹配的URD（n= 246）和MRD（n=187）RIC HSCT治疗血液系统恶性肿瘤。疾病包括：AML（127）、NHL（71）、CLL（68）、MDS（64）、HD（40）、CML（25）、MM（23）、MPD（12）、ALL（7）、其他白血病（1）。所有患者均接受了统一的氟达拉滨和静脉注射白消安预处理，并使用他克莫司/mini-MTX或他克莫司/西罗莫司+/− mini-MTX预防GVHD。与MRD相比，无关供体更年轻（中位年龄：33岁vs. 52岁，p<0.0001），提供的CD 34+产物更大（输注的中位CD 34+细胞：8.7 × 106/kg vs. 7.5 × 106/kg，p=0.002）。两个队列的疾病分布、疾病风险、既往移植和CMV状态相似。URD和MRD中II-IV级急性GVHD（第+180天）、2年慢性GVHD和2年非复发死亡率（NRM）的累积发生率分别为20%和16%、55%和50%以及8%和6%（p=NS）。URD组2年累积复发率较低，分别为52%和65%（p=0.005）。中位随访时间为26.5和35.8个月，非亲缘供者移植的2年无进展生存期（PFS）明显更好，URD为39.5%，MRD为29%（p= 0.01）。URD的2年总生存率为56%，MRD为50%（p=0.53）。在多变量分析中，URD与较低的复发风险（HR 0.67，p =0.002）和上级的PFS（HR 0.69，p=0.002）相关。这些结果表明，URD与更大的GVL活性比MRD，并可能有实践改变的影响，未来的供体选择在RIC HSCT。
As success of reduced intensity conditioning (RIC) hematopoietic stem cell transplantation (HSCT) relies primarily on graft-versus-leukemia (GVL) activity, increased minor HLA disparity in unrelated compared to related donors could have a significant impact on transplant outcomes. To assess whether use of unrelated donors (URD) engenders more potent GVL in RIC HSCT compared to matched related donors (MRD), we retrospectively studied 433 consecutive T-replete 6/6 HLA matched URD (n= 246) and MRD (n=187) RIC HSCT for hematologic malignancies at our institution. Diseases included: AML(127), NHL(71), CLL (68), MDS (64), HD(40), CML (25), MM(23), MPD (12), ALL(7), other leukemia (1). All received uniform fludarabine and intravenous busulfan conditioning, and GVHD prophylaxis with tacrolimus/mini-MTX or tacrolimus/sirolimus +/− mini-MTX. Unrelated donors were younger compared to MRD (median age: 33 yrs vs. 52 yrs, p<0.0001), and provided larger CD34+ products (median CD34+ cells infused: 8.7 × 106/kg vs. 7.5 × 106/kg, p=0.002). Distribution of diseases, disease risk, prior transplant, and CMV status was similar in both cohorts. Cumulative incidence of grade II–IV acute GVHD (at day+180), 2 year-chronic GVHD, and 2-year non-relapse mortality (NRM) were 20% vs. 16%, 55% vs. 50%, and 8% vs. 6% in URD and MRD, respectively (p=NS). Cumulative incidence of relapse at 2 years was lower in URD, 52% vs. 65% (p=0.005). With median follow-up of 26.5 and 35.8 months, 2-yr progression free survival (PFS) was significantly better in unrelated donor transplants, 39.5% for URD and 29% for MRD (p= 0.01). Overall survival at 2 years were 56% for URD vs. 50% for MRD (p=0.53). In multivariable analysis, URD was associated with a lower risk of relapse (HR 0.67, p =0.002) and superior PFS (HR 0.69, p=0.002). These results suggest that URD is associated with greater GVL activity than MRD, and could have practice changing impact on future donor selection in RIC HSCT.
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影响因子：
39.2
作者：
MARKS, DI;CULLIS, JO;GOLDMAN, JM
通讯作者：
GOLDMAN, JM
影响因子：
20.3
作者：
Maris, MB;Sandmaier, BM;Maloney, DG
通讯作者：
Maloney, DG
影响因子：
20.3
作者：
Alyea, EP;Kim, HT;Soiffer, RJ
通讯作者：
Soiffer, RJ
影响因子：
20.3
作者：
Slavin, S;Nagler, A;Or, R
通讯作者：
Or, R
影响因子：
4.3
作者：
Ho, Vincent T.;Aldridge, Julie;Alyea, Edwin P.
通讯作者：
Alyea, Edwin P.