Ando Taiki, Suzuki Taisei, Ishiyama Yasufumi, Koyama Satoshi, Tachibana Takayoshi, Tanaka Masatsugu, Kanamori Heiwa, Nakajima Hideaki
Department of Hematology, Kanagawa Cancer Center, Yokohama, Japan.
Department of Hematology, Kanagawa Cancer Center, Yokohama, Japan.
Biol Blood Marrow Transplant. 2020 Jan;26(1):171-177. doi: 10.1016/j.bbmt.2019.09.028. Epub 2019 Sep 26.
Cytomegalovirus (CMV) reactivation and natural killer (NK) cell reconstitution are well-recognized immunologic events occurring after allogeneic stem cell transplantation (allo-SCT). We aimed to study the outcome of CMV reactivation (CMVR) and NK cell reconstitution in patients with hematologic malignancies after allo-SCT. We retrospectively studied 246 adult patients (152 men, 94 women; median age, 51 years [range, 18 to 69]) who underwent allo-SCT for hematologic malignancies at the Kanagawa Cancer Center. CMVR was defined as initiation of preemptive CMV therapy after pp65 antigenemia surveillance. All patients' lymphocyte subsets were monitored by flow cytometry at 180, 365, and 730 days post-transplant. The median follow-up period was 3.2 years (range, .8 to 9.6 years). CMVR occurred in 141 patients (57%) at a median of 45 days (range, 15 to 93). In patients without CMVR (CMVR-) versus those with CMVR (CMVR+), 5-year overall survival (OS), nonrelapse mortality (NRM), and cumulative incidence of relapse (CIR) were 79% versus 55% (P < .001), 3% versus 16% (P = .012), and 28% versus 38% (P = .09), respectively. CD8 T cell and CD3CD56 NK cell subset were higher in CMVR+ patients at day 100 post-transplant. Multivariate analysis showed that adverse factors for OS were represented by no remission, CMVR, and lower CD16CD57NK cell counts. Overall, a higher NK cell subset significantly contributed to a lower CIR. Among subgroups of CMVR+ patients, CD16CD57NK cells represented a favorable factor for OS, NRM, and CIR. CMVR was an adverse event after allo-SCT. NK cell reconstitution may contribute to improved outcomes, especially in CMVR+ subgroups.
巨细胞病毒(CMV)再激活和自然杀伤(NK)细胞重建是异基因造血干细胞移植(allo-SCT)后公认的免疫事件。我们旨在研究allo-SCT后血液系统恶性肿瘤患者CMV再激活(CMVR)和NK细胞重建的结果。我们回顾性研究了246例成年患者(152例男性,94例女性;中位年龄51岁[范围18至69岁]),这些患者在神奈川癌症中心接受了allo-SCT治疗血液系统恶性肿瘤。CMVR定义为在pp65抗原血症监测后开始抢先CMV治疗。在移植后180、365和730天通过流式细胞术监测所有患者的淋巴细胞亚群。中位随访期为3.2年(范围0.8至9.6年)。141例患者(57%)发生CMVR,中位时间为45天(范围15至93天)。在无CMVR(CMVR-)患者与有CMVR(CMVR+)患者中,5年总生存率(OS)、非复发死亡率(NRM)和累积复发率(CIR)分别为79%对55%(P<0.001)、3%对16%(P = 0.012)和28%对38%(P = 0.09)。移植后100天时,CMVR+患者的CD8 T细胞和CD3CD56 NK细胞亚群较高。多因素分析显示,OS的不良因素为未缓解、CMVR和较低的CD16CD57NK细胞计数。总体而言,较高的NK细胞亚群显著有助于降低CIR。在CMVR+患者亚组中,CD16CD57NK细胞是OS、NRM和CIR的有利因素。CMVR是allo-SCT后的不良事件。NK细胞重建可能有助于改善预后,尤其是在CMVR+亚组中。