Li Jianqiang, Nicoud Ian, Blake Joseph, Oliver David, Cox Emily, Heimfeld Shelly, Milano Filippo, Imren Suzan, Delaney Colleen
Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington.
Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington; Department of Medicine, University of Washington, Seattle, Washington.
Biol Blood Marrow Transplant. 2017 Mar;23(3):412-419. doi: 10.1016/j.bbmt.2016.12.625. Epub 2016 Dec 19.
Cord blood transplantation (CBT) recipients are at increased risk for delayed engraftment and primary graft failure, complications that are often indistinguishable early post-transplantation. Current assays fail to accurately identify recipients with slow hematopoietic recovery and distinguish them from those with pending graft failure. To address this, we prospectively examined the kinetics of immune cell subset recovery in the peripheral blood of 39 patients on days +7 and +14 after double-unit CBT (dCBT) by multiparametric flow cytometry analysis, which we term real-time immunophenotyping (RTIP). RTIP analysis at day +14 revealed distinctive patterns of reconstitution and, importantly, identified patients with slow hematopoietic recovery who went on to engraft. Strikingly, higher absolute numbers of circulating monocytes and natural killer cells at day +14 were predictive of engraftment, but only the absolute number of circulating monocytes was significantly correlated with time to engraftment. This is the first evidence that RTIP on patient peripheral blood mononuclear cells early after dCBT is technically feasible and can be used as a "signature" for predicting the kinetics of hematopoietic recovery. Furthermore, RTIP is a time- and cost-efficient methodology that has the potential to become a clinically feasible diagnostic tool to guide therapeutic interventions in high-risk patients; therefore, its utility should be evaluated in a large cohort of patients.
脐血移植（CBT）受者发生植入延迟和原发性移植物失败的风险增加，这些并发症在移植后早期往往难以区分。目前的检测方法无法准确识别造血恢复缓慢的受者，也无法将他们与即将发生移植物失败的受者区分开来。为了解决这个问题，我们通过多参数流式细胞术分析，对39例接受双单位CBT（dCBT）的患者在第+7天和+14天外周血中免疫细胞亚群恢复的动力学进行了前瞻性研究，我们将其称为实时免疫表型分析（RTIP）。第+14天的RTIP分析揭示了独特的重建模式，重要的是，识别出了造血恢复缓慢但最终成功植入的患者。引人注目的是，第+14天循环单核细胞和自然杀伤细胞的绝对数量较高可预测植入情况，但只有循环单核细胞的绝对数量与植入时间显著相关。这是首个证据表明，dCBT后早期对患者外周血单个核细胞进行RTIP在技术上是可行的，并且可以用作预测造血恢复动力学的“标志物”。此外，RTIP是一种省时且经济高效的方法，有潜力成为一种临床上可行的诊断工具，以指导对高危患者的治疗干预；因此，应在大量患者队列中评估其效用。
