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

Research output: Contribution to journalReview article

2 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)186-194
Number of pages9
JournalTransfusion Medicine Reviews
Volume32
Issue number3
DOIs
Publication statusPublished - Jul 1 2018

Fingerprint

Hematopoietic Stem Cells
Stem cells
Multicenter Studies
Peripheral Blood Stem Cell Transplantation
Dimethyl Sulfoxide
Blood
Odds Ratio
Fetal Blood
Transplantation
Plasma Cells
Bone Marrow Transplantation
Hypersensitivity
Blood Component Transfusion
Blood Safety
Cell Hypoxia
Hematopoietic Stem Cell Transplantation
Anaphylaxis
Bone
Nausea
Vomiting

Keywords

  • Adverse events
  • Hematopoietic stem cell product
  • Hematopoietic stem cell transplantation
  • Hemovigilance
  • Infusion

ASJC Scopus subject areas

  • Hematology
  • Clinical Biochemistry
  • Biochemistry, medical

Cite this

Ikeda, K., Ohto, H., Okuyama, Y., Yamada-Fujiwara, M., Kanamori, H., Fujiwara, S. I., ... Tanosaki, R. (2018). Adverse Events Associated With Infusion of Hematopoietic Stem Cell Products: A Prospective and Multicenter Surveillance Study. Transfusion Medicine Reviews, 32(3), 186-194. https://doi.org/10.1016/j.tmrv.2018.05.005

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

In: Transfusion Medicine Reviews, Vol. 32, No. 3, 01.07.2018, p. 186-194.

Research output: Contribution to journalReview article

Ikeda, K, Ohto, H, Okuyama, Y, Yamada-Fujiwara, M, Kanamori, H, Fujiwara, SI, Muroi, K, Mori, T, Kasama, K, Iseki, T, Nagamura-Inoue, T, Fujii, N, Ashida, T, Kameda, K, Kanda, J, Hirose, A, Takahashi, T, Nagai, K, Minakawa, K & Tanosaki, R 2018, 'Adverse Events Associated With Infusion of Hematopoietic Stem Cell Products: A Prospective and Multicenter Surveillance Study', Transfusion Medicine Reviews, vol. 32, no. 3, pp. 186-194. https://doi.org/10.1016/j.tmrv.2018.05.005
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. / Adverse Events Associated With Infusion of Hematopoietic Stem Cell Products : A Prospective and Multicenter Surveillance Study. In: Transfusion Medicine Reviews. 2018 ; Vol. 32, No. 3. pp. 186-194.
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T2 - A Prospective and Multicenter Surveillance Study

AU - Ikeda, Kazuhiko

AU - Ohto, Hitoshi

AU - Okuyama, Yoshiki

AU - Yamada-Fujiwara, Minami

AU - Kanamori, Heiwa

AU - Fujiwara, Shin ichiro

AU - Muroi, Kazuo

AU - Mori, Takehiko

AU - Kasama, Kinuyo

AU - Iseki, Tohru

AU - Nagamura-Inoue, Tokiko

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AU - Ashida, Takashi

AU - Kameda, Kazuaki

AU - Kanda, Junya

AU - Hirose, Asao

AU - Takahashi, Tsutomu

AU - Nagai, Kazuhiro

AU - Minakawa, Keiji

AU - Tanosaki, Ryuji

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N2 - 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.

AB - 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.

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