血液系统恶性肿瘤患者干细胞移植后亚临床造血的影像学研究：一项前瞻性初步研究
Imaging of subclinical haemopoiesis after stem-cell transplantation in patients with haematological malignancies: a prospective pilot study.
作者信息
Williams Kirsten M, Holter-Chakrabarty Jennifer, Lindenberg Liza, Duong Quyen, Vesely Sara K, Nguyen Chuong T, Havlicek Joseph P, Kurdziel Karen, Gea-Banacloche Juan, Lin Frank I, Avila Daniele N, Selby George, Kanakry Christopher G, Li Shibo, Scordino Teresa, Adler Stephen, Bollard Catherine M, Choyke Peter, Gress Ronald E
机构信息
Children's Research Institute, Children's National Health System, Washington, DC, USA.
Stephenson Cancer Center, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.
出版信息
Lancet Haematol. 2018 Jan;5(1):e44-e52. doi: 10.1016/S2352-3026(17)30215-6. Epub 2017 Dec 14.
BACKGROUND
Haemopoietic stem-cell transplantation (HSCT) eradicates host haemopoiesis before venous infusion of haemopoietic stem cells (HSCs). The pathway to cellular recovery has been difficult to study in human beings because of risks associated with interventions during aplasia. We investigated whether F-fluorothymidine (F-FLT) imaging was safe during allogenic HSCT and allowed visualisation of early cellular proliferation and detection of patterns of cellular engraftment after HSCT.
METHODS
Eligible patients were aged 18-55 years, had high-risk haematological malignancies. All patients underwent myeloablation followed by HSCT. The imaging primary endpoint was detection of early subclinical engraftment after HSCT with F-FLT PET or CT. Imaging was done 1 day before and 5 or 9, and 28 days, and 1 year after HSCT. This study is registered with ClinicalTrials.gov, number NCT01338987.
FINDINGS
Between April 1, 2014, and Dec 31, 2015, 23 patients were enrolled and assessable for toxic effects after completing accrual. F-FLT was not associated with any adverse events or delayed engraftment. F-FLT imaging objectively identified subclinical bone-marrow recovery within 5 days of HSC infusion, which was up to 20 days before engraftment became clinically evident. Quantitatively, F-FLT intensity differed significantly between myeloablative infusion before HSCT and subclinical HSC recovery (p=0·00031). F-FLT biodistribution over time revealed a previously unknown path of cellular recovery of haemopoiesis in vivo that mirrored fetal ontogeny.
INTERPRETATION
F-FLT allowed quantification and tracking of subclinical bone-marrow repopulation in human beings and revealed new insights into the biology of HSC recovery after HSCT.
FUNDING
National Institutes of Health, Ben's Run/Ben's Gift, Albert and Elizabeth Tucker Foundation, Mex Frates Leukemia Fund, Jones Family fund, and Oklahoma Center for Adult Stem Cell Research.
背景
造血干细胞移植（HSCT）在静脉输注造血干细胞（HSC）之前会根除宿主造血功能。由于再生障碍期间干预相关的风险，人类细胞恢复途径一直难以研究。我们调查了氟代胸腺嘧啶核苷（F-FLT）成像在异基因HSCT期间是否安全，以及是否能可视化早期细胞增殖并检测HSCT后细胞植入模式。
方法
符合条件的患者年龄在18 - 55岁之间，患有高危血液系统恶性肿瘤。所有患者均接受清髓治疗，随后进行HSCT。成像的主要终点是通过F-FLT PET或CT检测HSCT后早期亚临床植入。在HSCT前1天、5或9天、28天以及1年后进行成像。本研究已在ClinicalTrials.gov注册，编号为NCT01338987。
研究结果
在2014年4月1日至2015年12月31日期间，招募了23名患者，在完成入组后可评估毒性作用。F-FLT与任何不良事件或植入延迟均无关联。F-FLT成像客观地识别出HSC输注后5天内的亚临床骨髓恢复，这比植入在临床上变得明显早多达20天。定量分析显示，HSCT前清髓输注与亚临床HSC恢复之间的F-FLT强度存在显著差异（p = 0·00031）。F-FLT随时间的生物分布揭示了体内造血细胞恢复的一条此前未知的途径，该途径与胎儿个体发育相似。
解读
F-FLT能够对人类亚临床骨髓再填充进行定量和追踪，并揭示了HSCT后HSC恢复生物学的新见解。
资金来源
美国国立卫生研究院、本氏跑步/本氏礼物基金、阿尔伯特和伊丽莎白·塔克基金会、梅克斯·弗拉茨白血病基金、琼斯家族基金以及俄克拉荷马成人干细胞研究中心。
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