Nakamura Toru, Masuda Atsutaka, Kako Makoto, Enomoto Hirayuki, Kaibori Masaki, Fujita Yasuyuki, Tanizawa Kyoko, Ioji Tetsuya, Fujimori Yoshihiro, Fukami Kei, Hazama Takuma, Iwamoto Hideki, Kako Yasukazu, Kobayashi Kaoru, Koga Hironori, Nagafuji Koji, Ohtake Takayasu, Suzuki Hiroyuki, Takashima Tomoyuki, Tsukiyama Toshitaka, Uojima Haruki, Yamahara Kenichi, Yamakado Koichiro, Yamamoto Hidekazu, Yoh Kazunori, Yoshihara Satoshi, Kawamoto Atsuhiko, Nishiguchi Shuhei, Kobayashi Shuzo, Torimura Takuji, Kawaguchi Takumi
Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine, Kurume, Fukuoka, 8300011, Japan.
Liver Cancer Research Division, Research Center for Innovative Cancer Therapy, Kurume University, Kurume, Fukuoka, 8300011, Japan.
Regen Ther. 2024 May 4;27:455-463. doi: 10.1016/j.reth.2024.04.018. eCollection 2024 Dec.
In this multicenter clinical study, we aimed to investigate the efficacy and safety of the transhepatic arterial administration of granulocyte-colony stimulating factor (G-CSF)-mobilized autologous peripheral blood (PB)-CD34 cells compared with standard therapy in patients with decompensated cirrhosis type C.
Patients were randomly assigned (2:1) to the CD34 cell transplant (CD34 cell) or standard-of-care (SOC) group and followed up for 52 weeks. The primary endpoints were the non-progression rate of Child-Pugh (CP) scores at 24 weeks post-enrollment and the safety of the protocol treatment.
Fourteen patients (CD34 cell group: 10; SOC group: 4) were enrolled. CP scores at 24 weeks had a non-progression rate of 90% in the CD34 cell group and 100% in the SOC group, with no significant difference between groups. Importantly, 4 out of 10 patients in the CD34 cell group exhibited an improvement from decompensated to compensated cirrhosis, whereas all patients in the SOC group remained in decompensated cirrhosis. With regard to secondary endpoints, a trend toward increased serum albumin levels in the CD34 cell group was noted. Serious adverse events (SAEs) occurred in three patients in the CD34 cell group and in one patient in the SOC group. No causal relationship was observed between all SAEs and G-CSF, leukapheresis, or cell transplantation in the CD34 cell group. No patients died and no hepatocellular carcinoma occurred within the study period.
PB-CD34 cell infusion therapy may have the potential to circumvent the decompensated stage of cirrhosis, thus avoiding the need for liver transplantation.
在这项多中心临床研究中，我们旨在研究经肝动脉输注粒细胞集落刺激因子（G-CSF）动员的自体外周血（PB）-CD34细胞与标准治疗相比，对丙型失代偿期肝硬化患者的疗效和安全性。
患者被随机分配（2:1）至CD34细胞移植组（CD34细胞组）或标准治疗组（SOC组），并随访52周。主要终点为入组后24周时Child-Pugh（CP）评分的无进展率及方案治疗的安全性。
共纳入14例患者（CD34细胞组：10例；SOC组：4例）。CD34细胞组24周时CP评分的无进展率为90%，SOC组为100%，两组间无显著差异。重要的是，CD34细胞组10例患者中有4例从失代偿期肝硬化改善为代偿期肝硬化，而SOC组所有患者仍处于失代偿期肝硬化。关于次要终点，CD34细胞组血清白蛋白水平有升高趋势。CD34细胞组有3例患者发生严重不良事件（SAE），SOC组有1例患者发生SAE。在CD34细胞组中，未观察到所有SAE与G-CSF、白细胞分离术或细胞移植之间存在因果关系。研究期间无患者死亡，也未发生肝细胞癌。
PB-CD34细胞输注疗法可能有潜力绕过肝硬化的失代偿期，从而避免肝移植的需要。
