Transplantation of ex vivo expanded cord blood cells using the copper chelator tetraethylenepentamine:: a phase I/II clinical trial
Transplantation of ex vivo expanded cord blood cells using the copper chelator tetraethylenepentamine:: a phase I/II clinical trial
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DOI：
10.1038/sj.bmt.1705979
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发表时间：
2008-05-01
影响因子：
4.8
通讯作者：
Shpall, E. J.
中科院分区：
文献类型：
--
作者：
de Lima, M.;McMannis, J.;Shpall, E. J.
铜络合剂四乙基五胺(TEPA；StemEx)可抑制体外培养的造血细胞的分化，导致早期祖细胞优先扩增。为探讨CD133+脐血造血祖细胞在含有干细胞因子、Flt-3配体、IL-6、血小板生成素和TEPA的培养液中移植的可行性和安全性，进行了I/II期试验。对10名晚期恶性血液病患者进行了移植，移植的是原本被冷冻成两部分的CB单位。较小的组份在体外培养21d，并在输注较大的未经处理的组份后24小时移植。除两个单位外，所有单位扩增前每公斤共含有2×10(7)个有核细胞(TNCs)。所有供受者对在一个或两个人类白细胞抗原基因座上都不匹配。首次缓解9例，中位年龄21岁，体重68.5 kg。跨国公司的平均倍数扩张为219倍(范围为2-620)。CD34+细胞数平均增加6个(超过整个单位的CD34+细胞含量)。尽管每公斤输注的跨国公司较低(中位数=1.8x10(7)/公斤)，但仍有9名患者植入。中性粒细胞和血小板植入的中位时间分别为30天(16-46天)和48天(35-105天)。无3-4级急性移植物抗宿主病(GVHD)病例，100天存活率为90%。这一战略是可行的。
The copper chelator tetraethylenepentamine (TEPA; StemEx) was shown to attenuate the differentiation of ex vivo cultured hematopoietic cells resulting in preferential expansion of early progenitors. A phase I/II trial was performed to test the feasibility and safety of transplantation of CD133+ cord blood (CB) hematopoietic progenitors cultured in media containing stem cell factor, FLT-3 ligand, interleukin-6, thrombopoietin and TEPA. Ten patients with advanced hematological malignancies were transplanted with a CB unit originally frozen in two fractions. The smaller fraction was cultured ex vivo for 21 days and transplanted 24 h after infusion of the larger unmanipulated fraction. All but two units contained < 2 x 10(7) total nucleated cells (TNCs) per kilogram pre-expansion. All donor-recipient pairs were mismatched for one or two HLA loci. Nine patients were beyond first remission; median age and weight were 21 years and 68.5 kg. The average TNCs fold expansion was 219 (range, 2-620). Mean increase of CD34+ cell count was 6 (over the CD34+ cell content in the entire unit). Despite the low TNCs per kilogram infused (median = 1.8 x 10(7)/ kg), nine patients engrafted. Median time to neutrophil and platelet engraftment was 30 (range, 16-46) and 48 (range, 35-105) days. There were no cases of grades 3-4 acute graft-versus-host disease (GVHD) and 100-day survival was 90%. This strategy is feasible.