Successful hematopoietic stem cell mobilization and apheresis collection using plerixafor alone in sickle cell patients
Successful hematopoietic stem cell mobilization and apheresis collection using plerixafor alone in sickle cell patients
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DOI：
10.1182/bloodadvances.2018016725
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发表时间：
2018-10-09
期刊：
影响因子：
7.5
通讯作者：
Biffi, Alessandra
中科院分区：
文献类型：
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作者：
Esrick, Erica B.;Manis, John P.;Biffi, Alessandra
基于基因工程自体造血干细胞和祖细胞（HSPC）的镰状细胞病（SCD）的新疗法关键依赖于安全有效的细胞获取策略。我们试图评估普乐沙福用于SCD输血患者HSC动员的安全性和有效性。招募了6例成人SCD患者接受普乐沙福单次给药，以低于标准（180 μ g/kg）和标准（240 μ g/kg）剂量进行检测，随后监测外周血和单采血液成分术采集的CD 34（+）细胞。手术安全且耐受性良好。动员是成功的，与低剂量组相比，标准组的外周血CD 34（+）细胞计数更高。在我们的6名供体中，我们通过使用深层采集界面并在普乐沙福给药后4小时内开始单采，改善了单采细胞采集结果。在接受普乐沙福单次标准剂量并遵循优化采集方案的受试者中，获得了高达24.5 x 10（6）个CD 34（+）细胞/kg的产量。有趣的是，收集的CD 34（+）细胞富含免疫表型定义的长期HSC和早期祖细胞。因此，我们证明了普乐沙福可以安全地用于SCD患者，以获得足够的HSC用于基因治疗。
Novel therapies for sickle cell disease (SCD) based on genetically engineered autologous hematopoietic stemand progenitor cells (HSPCs) are criticallydependentona safeandeffective strategy for cell procurement. We sought to assess the safety and efficacy of plerixafor when used in transfused patients with SCD for HSCmobilization. Six adult patients with SCD were recruited to receive a single dose of plerixafor, tested at lower than standard (180 mu g/kg) and standard (240 mu g/kg) doses, followed by CD34(+) cell monitoring in peripheral blood and apheresis collection. The procedures were safe and well-tolerated. Mobilization was successful, with higher peripheral CD34(+) cell counts in the standard vs the low-dose group. Among our 6 donors, we improved apheresis cell collection results by using a deep collection interface and starting apheresis within 4 hours after plerixafor administration. In the subjects who received a single standard dose of plerixafor and followed the optimized collection protocol, yields of up to 24.5 x 10(6) CD34(+) cells/kg were achieved. Interestingly, the collected CD34(+) cells were enriched in immunophenotypically defined long-term HSCs and early progenitors. Thus, we demonstrate that plerixafor can be employed safely in patients with SCD to obtain sufficient HSCs for potential use in gene therapy.