Adverse Events Associated With Infusion of Hematopoietic Stem Cell Products: A Prospective and Multicenter Surveillance Study

Kazuhiko Ikeda; Hitoshi Ohto; Yoshiki Okuyama; Minami Yamada-Fujiwara; Heiwa Kanamori; Shin-Ichiro Fujiwara; Kazuo Muroi; Takehiko Mori; Kinuyo Kasama; Tohru Iseki; Tokiko Nagamura-Inoue; Nobuharu Fujii; Takashi Ashida; Kazuaki Kameda; Junya Kanda; Asao Hirose; Tsutomu Takahashi; Kazuhiro Nagai; Keiji Minakawa; Ryuji Tanosaki

doi:10.1016/j.tmrv.2018.05.005

Adverse Events Associated With Infusion of Hematopoietic Stem Cell Products: A Prospective and Multicenter Surveillance Study

Transfus Med Rev. 2018 Jun 1:S0887-7963(18)30023-3. doi: 10.1016/j.tmrv.2018.05.005. Online ahead of print.

Authors

Kazuhiko Ikeda¹, Hitoshi Ohto², Yoshiki Okuyama³, Minami Yamada-Fujiwara⁴, Heiwa Kanamori⁵, Shin-Ichiro Fujiwara⁶, Kazuo Muroi⁷, Takehiko Mori⁸, Kinuyo Kasama⁹, Tohru Iseki¹⁰, Tokiko Nagamura-Inoue¹¹, Nobuharu Fujii¹², Takashi Ashida¹³, Kazuaki Kameda¹⁴, Junya Kanda¹⁴, Asao Hirose¹⁵, Tsutomu Takahashi¹⁶, Kazuhiro Nagai¹⁷, Keiji Minakawa¹⁸, Ryuji Tanosaki¹⁹

Affiliations

¹ 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. Electronic address: [email protected].
² 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.
³ Cell Therapy Committee, The Japan Society of Transfusion Medicine and Cell Therapy, Tokyo, Japan; Division of Transfusion and Cell Therapy, Tokyo Metropolitan Komagome Hospital, Tokyo, Japan.
⁴ Division of Blood Transfusion and Cell Therapy, Tohoku University Hospital, Sendai, Japan.
⁵ Cell Therapy Committee, The Japan Society of Transfusion Medicine and Cell Therapy, Tokyo, Japan; Department of Hematology, Kanagawa Cancer Center, Yokohama, Japan.
⁶ Division of Hematology, Department of Medicine, Jichi Medical University, Shimotsuke, Japan.
⁷ Cell Therapy Committee, The Japan Society of Transfusion Medicine and Cell Therapy, Tokyo, Japan; Cell Transplantation and Transfusion, Jichi Medical University, Tochigi, Japan.
⁸ Division of Hematology, Department of Medicine, Keio University School of Medicine, Tokyo, Japan.
⁹ Department of Transfusion Medicine, Tokyo Jikei University Hospital, Tokyo, Japan.
¹⁰ Cell Therapy Committee, The Japan Society of Transfusion Medicine and Cell Therapy, Tokyo, Japan; Department of Transfusion Medicine and Cell Therapy, Chiba University Hospital, Chiba, Japan.
¹¹ Cell Therapy Committee, The Japan Society of Transfusion Medicine and Cell Therapy, Tokyo, Japan; Institution of Medical Science, University of Tokyo, Tokyo, Japan.
¹² Department of Transfusion Medicine, Okayama University Hospital, Okayama-shi, Japan.
¹³ Center for Transfusion and Cell Therapy, Kindai University Hospital, Osakasayama, Japan.
¹⁴ Division of Hematology, Saitama Medical Center, Jichi Medical University, Saitama, Japan.
¹⁵ Department of Hematology, Osaka City University, Osaka, Japan.
¹⁶ Department of Oncology/Hematology, Shimane University Hospital, Shimane, Japan.
¹⁷ Transfusion and Cell Therapy Unit, Nagasaki University Hospital, Nagasaki, Japan.
¹⁸ Department of Blood Transfusion and Transplantation Immunology, Fukushima Medical University, Fukushima, Japan.
¹⁹ Cell Therapy Committee, The Japan Society of Transfusion Medicine and Cell Therapy, Tokyo, Japan.

PMID: 29891441
DOI: 10.1016/j.tmrv.2018.05.005

Abstract

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.

Keywords: Adverse events; Hematopoietic stem cell product; Hematopoietic stem cell transplantation; Hemovigilance; Infusion.

Publication types

Review