Milano F, Thur L A, Blake J, Delaney C
Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, United States.
Department of Medicine, University of Washington School of Medicine, Seattle, WA, United States.
Front Cell Dev Biol. 2022 Apr 4;10:835793. doi: 10.3389/fcell.2022.835793. eCollection 2022.
Recipients of myeloablative cord blood transplants (CBT) are known to experience delayed hematopoietic recovery and an increased risk of transplant related mortality (TRM). We developed methods for expansion and cryopreservation of CB stem and progenitor cells. 15 patients with hematologic malignancies were enrolled in this single center phase II trial between September 2010 and August 2012 to assess the safety of infusing a non-HLA-matched expanded CB product to bolster a conventional CBT. On the day of transplant, an infusion of the expanded CB product followed the primary graft (1 or 2 unmanipulated CB units). All patients engrafted. Median time to neutrophil and platelet recovery was 19 and 35 days, respectively. Early myelomonocytic recovery was almost entirely due to cells arising from the non-HLA-matched expansion product and were no longer detected at day 14 in all but 2 patients. The probability of 3-years disease free survival was 86%. No TRM was observed throughout the study period, and only 2 patients relapsed. All patients presented with grade II acute graft-versus-host disease (aGVHD) at a median time of 32 days, with no grade III-IV aGVHD observed. At 2 years only 2 patients remain on immunosuppressive therapy for mild chronic GVHD. This phase II safety study demonstrate that infusion of an off-the-shelf non-HLA-matched expanded CB product in addition to a conventional CB graft was safe and led to sustained myeloid recovery. Based on these encouraging results, a prospective multicenter randomized trial utilizing this product has been conducted and results will be soon released. ClinicalTrials.gov Identifier: NCT01175785.
已知接受清髓性脐血移植（CBT）的患者会经历造血恢复延迟以及移植相关死亡率（TRM）增加的情况。我们开发了脐血干细胞和祖细胞的扩增及冷冻保存方法。2010年9月至2012年8月期间，15例血液系统恶性肿瘤患者参与了这项单中心II期试验，以评估输注非HLA匹配的扩增脐血产品来支持传统CBT的安全性。在移植当天，在主要移植物（1或2个未处理的脐血单位）之后输注扩增的脐血产品。所有患者均实现植入。中性粒细胞和血小板恢复的中位时间分别为19天和35天。早期髓单核细胞恢复几乎完全归因于非HLA匹配扩增产品产生的细胞，除2例患者外，在第14天时均未再检测到这些细胞。3年无病生存率为86%。在整个研究期间未观察到TRM，仅有2例患者复发。所有患者在中位时间32天时均出现II级急性移植物抗宿主病（aGVHD），未观察到III - IV级aGVHD。在2年时，仅有2例患者因轻度慢性GVHD仍在接受免疫抑制治疗。这项II期安全性研究表明，除了传统的脐血移植物外，输注现成的非HLA匹配扩增脐血产品是安全的，并导致持续的髓系恢复。基于这些令人鼓舞的结果，已开展了一项使用该产品的前瞻性多中心随机试验，结果将很快公布。ClinicalTrials.gov标识符：NCT01175785。
