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移植两个部分人类白细胞抗原(HLA)匹配的脐带血单位以提高血液系统恶性肿瘤成年患者的植入率。

Transplantation of 2 partially HLA-matched umbilical cord blood units to enhance engraftment in adults with hematologic malignancy.

作者信息

Barker Juliet N, Weisdorf Daniel J, DeFor Todd E, Blazar Bruce R, McGlave Philip B, Miller Jeffrey S, Verfaillie Catherine M, Wagner John E

机构信息

Blood and Marrow Transplant Program, Division of Medical and Pediatric Oncology, University of Minnesota, Box 480, 420 Delaware St SE, Minneapolis, MN 55455, USA.

出版信息

Blood. 2005 Feb 1;105(3):1343-7. doi: 10.1182/blood-2004-07-2717. Epub 2004 Oct 5.

Abstract

Limited umbilical cord blood (UCB) cell dose compromises the outcome of adult UCB transplantation. Therefore, to augment graft cell dose, we evaluated the safety of the combined transplantation of 2 partially human leukocyte antigen (HLA)-matched UCB units. Twenty-three patients with high-risk hematologic malignancy (median age, 24 years; range, 13-53 years) received 2 UCB units (median infused dose, 3.5 x 10(7) nucleated cell [NC]/kg; range, 1.1-6.3 x 10(7) NC/kg) after myeloablative conditioning. All evaluable patients (n = 21) engrafted at a median of 23 days (range, 15-41 days). At day 21, engraftment was derived from both donors in 24% of patients and a single donor in 76% of patients, with 1 unit predominating in all patients by day 100. Although neither nucleated or CD34(+) cell doses nor HLA-match predicted which unit would predominate, the predominating unit had a significantly higher CD3(+) dose (P < .01). Incidences of grades II-IV and III-IV acute GVHD were 65% (95% confidence interval [CI], 42%-88%) and 13% (95% CI, 0%-26%), respectively. Disease-free survival was 57% (95% CI, 35%-79%) at 1 year, with 72% (95% CI, 49%-95%) of patients alive if they received transplants while in remission. Therefore, transplantation of 2 partially HLA-matched UCB units is safe, and may overcome the cell-dose barrier that limits the use of UCB in many adults and adolescents.

摘要

脐带血(UCB)细胞剂量有限会影响成人UCB移植的效果。因此,为增加移植物细胞剂量,我们评估了联合移植两个部分人类白细胞抗原(HLA)匹配的UCB单位的安全性。23例高危血液系统恶性肿瘤患者(中位年龄24岁;范围13 - 53岁)在清髓性预处理后接受了两个UCB单位(中位输注剂量,3.5×10⁷有核细胞[NC]/kg;范围,1.1 - 6.3×10⁷ NC/kg)。所有可评估患者(n = 21)在中位23天(范围,15 - 41天)时实现植入。在第21天,24%的患者植入细胞来自两个供体,76%的患者来自单个供体,到第100天时所有患者中均有一个单位占主导。尽管有核细胞或CD34⁺细胞剂量以及HLA匹配均无法预测哪个单位会占主导,但占主导的单位CD3⁺剂量显著更高(P < 0.01)。II - IV级和III - IV级急性移植物抗宿主病(GVHD)的发生率分别为65%(95%置信区间[CI],42% - 88%)和13%(95% CI,0% - 26%)。1年时无病生存率为57%(95% CI,35% - 79%),如果患者在缓解期接受移植,则72%(95% CI,49% - 95%)的患者存活。因此,联合移植两个部分HLA匹配的UCB单位是安全的,并且可能克服限制许多成人和青少年使用UCB的细胞剂量障碍。

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