Ikeda Kazuhiko, Ohto Hitoshi, Okuyama Yoshiki, Yamada-Fujiwara Minami, Kanamori Heiwa, Fujiwara Shin-Ichiro, Muroi Kazuo, Mori Takehiko, Kasama Kinuyo, Iseki Tohru, Nagamura-Inoue Tokiko, Fujii Nobuharu, Ashida Takashi, Kameda Kazuaki, Kanda Junya, Hirose Asao, Takahashi Tsutomu, Nagai Kazuhiro, Minakawa Keiji, Tanosaki Ryuji
Cell Therapy Committee, The Japan Society of Transfusion Medicine and Cell Therapy, Tokyo, Japan; Department of Blood Transfusion and Transplantation Immunology, Fukushima Medical University, Fukushima, Japan.
Cell Therapy Committee, The Japan Society of Transfusion Medicine and Cell Therapy, Tokyo, Japan; Department of Blood Transfusion and Transplantation Immunology, Fukushima Medical University, Fukushima, Japan.
Transfus Med Rev. 2018 Jun 1. doi: 10.1016/j.tmrv.2018.05.005.
Adverse events (AEs) associated with blood transfusions, including component-specific red cell, platelet, and plasma products, have been extensively surveyed. In contrast, surveillance of AEs associated with hematopoietic stem cell (HSC) products in HSC transplantation (HSCT) has been less rigorous, even though HSC products include a diversity of immature and mature hematopoietic cells, substantial plasma, and dimethyl sulfoxide (DMSO) in the case of cryopreserved HSC products. HSC infusion-related AEs have been attributed to DMSO toxicity, but AEs associated with the infusion of noncryopreserved HSC products are not uncommon. To quantify the frequencies, types, and risk factors of HSC infusion-related AEs, we implemented national surveillance for AEs observed within 24 hours after infusion. Herein we report on 1125 HSCTs, including 570 peripheral blood stem cell transplantations (PBSCTs) (290 autologous [auto-] and 280 allogeneic [allo-]), 332 allo-bone marrow transplantations (allo-BMTs) and 223 allo-cord blood transplantations (allo-CBTs). Unexpectedly, incidences of grade ≥ 2 AEs were most frequent in allo-BMTs (37.7%) with no DMSO in any product compared with auto-/allo-PBSCTs (20.9%, P < .001) and allo-CBTs (19.3%, P < .001) typically cryopreserved with DMSO. Hypertension was most often noted in BMTs, whereas nausea/vomiting, fever, and allergic reactions were most frequent in allo-PBSCTs. In a multivariate analysis, a history of transfusion reactions was a risk factor for overall AEs in all HSCTs (odds ratio [OR] = 1.459, P = .045). For grade ≥ 2 AEs in allo-HSCTs, a history of transfusion reactions (OR = 1.551, P = .044) for overall AEs, and high infusion volume (OR = 7.544, P = .005) and allo-PBSCTs (versus BMTs, OR = 9.948, P = .002) for allergic reactions were identified as risk factors. These findings suggest that some factors unrelated to DMSO, such as allo-antigens, contribute to HSC infusion-related AEs. As severe AEs, a total of 117 grade ≥ 3 AEs were reported in 1125 HSCTs, including life-threatening complications in 3 (0.3%) HSCTs: 1 allo-CBT (anaphylaxis) and 2 allo-PBSCTs (hypoxia, kidney injury) with cryopreserved product. Our data show that HSC infusion risks vary by product, can be severe, and should be monitored with the same rigor as modern transfusion hemovigilance programs.
与输血相关的不良事件（AE），包括特定成分的红细胞、血小板和血浆制品，已得到广泛调查。相比之下，尽管造血干细胞（HSC）制品包括多种未成熟和成熟的造血细胞、大量血浆，以及冷冻保存的HSC制品中含有的二甲基亚砜（DMSO），但对造血干细胞移植（HSCT）中与HSC制品相关的AE的监测却不够严格。与HSC输注相关的AE被归因于DMSO毒性，但与非冷冻保存的HSC制品输注相关的AE并不罕见。为了量化与HSC输注相关的AE的频率、类型和风险因素，我们对输注后24小时内观察到的AE进行了全国性监测。在此，我们报告了1125例HSCT，包括570例外周血干细胞移植（PBSCT）（290例自体[auto-]和280例异基因[allo-]）、332例异基因骨髓移植（allo-BMT）和223例异基因脐血移植（allo-CBT）。出乎意料的是，与自体/异基因PBSCT（20.9%，P<0.001）和通常用DMSO冷冻保存的异基因CBT（19.3%，P<0.001）相比，任何制品中均无DMSO的异基因BMT中≥2级AE的发生率最高（37.7%）。高血压在BMT中最常被注意到，而恶心/呕吐、发热和过敏反应在异基因PBSCT中最常见。在多变量分析中，输血反应史是所有HSCT中总体AE的一个风险因素（比值比[OR]=1.459，P=0.045）。对于异基因HSCT中的≥2级AE，总体AE的输血反应史（OR=1.551，P=0.044），以及高输注量（OR=7.544，P=0.005）和过敏反应的异基因PBSCT（与BMT相比，OR=9.948，P=0.002）被确定为风险因素。这些发现表明，一些与DMSO无关的因素，如异基因抗原，会导致与HSC输注相关的AE。作为严重AE，在1125例HSCT中共报告了117例≥3级AE，包括3例（0.3%）HSCT中的危及生命的并发症：1例异基因CBT（过敏反应）和2例冷冻保存制品的异基因PBSCT（缺氧、肾损伤）。我们的数据表明，HSC输注风险因制品而异，可能很严重，应与现代输血血液警戒计划一样严格地进行监测。
