Adverse events following infusion of T cells for adoptive immunotherapy: A 10-year experience

Conrad Russell Cruz, Patrick J. Hanley, Hao Liu, Vicky Torrano, Yu Feng Lin, James A. Arce, Stephen Gottschalk, Barbara Savoldo, Gianpietro Dotti, Chrystal U. Louis, Ann M. Leen, Adrian P. Gee, Cliona M. Rooney, Malcolm K. Brenner, Catherine M. Bollard, Helen E. Heslop

Research output: Contribution to journalArticle

46 Citations (Scopus)

Abstract

Background aims. The Food and Drug Administration (FDA) currently recommends at least 4 h of recipient monitoring after T cell infusions to detect early infusion reactions. Recent catastrophic reactions to 'first-in-man' biologic agents have emphasized the importance of this rule for initial studies of new products. The value of such monitoring for better established agents is less obvious. Methods. We reviewed infusion-related adverse events (AE) following administration of ex vivo-expanded T cell products (antigen-specific cytotoxic T lymphocytes, allodepleted T cells, and genetically modified T cells) on investigational new drug (IND) studies in our center. Results. From 1998 to 2008, we infused 381 T cell products to 180 recipients, enrolled on 18 studies, receiving T cells targeting malignancies or post-transplant viral infections. There were no grade 34 infusion reactions during initial monitoring or 24-h follow-up. Twenty-four mild (grade 12) AE occurred in 21 infusions either during or immediately following infusion (up to 6 h), most commonly nausea and vomiting (10/24, 41.6%), probably because of the dimethyl sulfoxide cryoprotectant, and hypotension (20.8%), attributable to diphenhydramine pre-medication. Twenty-two additional non-severe events were reported within 24 h of infusion, most commonly culture-negative fever, chills and nausea. An increased risk of adverse events was associated with age [incidence rate ratio (IRR) 0.98; 95% confidence interval (CI) 0.961.00, P 0.05], while an increased risk of immediate infusion-related events was higher in patients reporting allergies (IRR 2.72, 95% CI 1.007.40, P 0.05); sex, disease type and T cell source (allogeneic or autologous) had no effect on frequency of adverse events. Conclusions. Infusion of these T cell products was safe in the outpatient setting and associated with no severe reactions, so monitoring for 1 h after infusion is probably sufficient. As many of the AE were attributable to diphenhydramine premedication, a lower dose (0.25 mg/kg) should be selected.

Original languageEnglish (US)
Pages (from-to)743-749
Number of pages7
JournalCytotherapy
Volume12
Issue number6
DOIs
StatePublished - Jan 1 2010
Externally publishedYes

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Adoptive Immunotherapy
antineoplaston A10
T-Lymphocytes
Diphenhydramine
Nausea
Confidence Intervals
Investigational Drugs
Chills
Premedication
Incidence
Biological Factors
Cytotoxic T-Lymphocytes
Virus Diseases
United States Food and Drug Administration
Dimethyl Sulfoxide
Hypotension
Vomiting
Hypersensitivity
Fever
Outpatients

Keywords

  • Adverse events
  • Cytotoxic T lymphocytes
  • EpsteinBarr virus
  • Infusion reaction
  • T cells

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Oncology
  • Genetics(clinical)
  • Cell Biology
  • Transplantation
  • Cancer Research

Cite this

Cruz, C. R., Hanley, P. J., Liu, H., Torrano, V., Lin, Y. F., Arce, J. A., ... Heslop, H. E. (2010). Adverse events following infusion of T cells for adoptive immunotherapy: A 10-year experience. Cytotherapy, 12(6), 743-749. https://doi.org/10.3109/14653241003709686

Adverse events following infusion of T cells for adoptive immunotherapy : A 10-year experience. / Cruz, Conrad Russell; Hanley, Patrick J.; Liu, Hao; Torrano, Vicky; Lin, Yu Feng; Arce, James A.; Gottschalk, Stephen; Savoldo, Barbara; Dotti, Gianpietro; Louis, Chrystal U.; Leen, Ann M.; Gee, Adrian P.; Rooney, Cliona M.; Brenner, Malcolm K.; Bollard, Catherine M.; Heslop, Helen E.

In: Cytotherapy, Vol. 12, No. 6, 01.01.2010, p. 743-749.

Research output: Contribution to journalArticle

Cruz, CR, Hanley, PJ, Liu, H, Torrano, V, Lin, YF, Arce, JA, Gottschalk, S, Savoldo, B, Dotti, G, Louis, CU, Leen, AM, Gee, AP, Rooney, CM, Brenner, MK, Bollard, CM & Heslop, HE 2010, 'Adverse events following infusion of T cells for adoptive immunotherapy: A 10-year experience', Cytotherapy, vol. 12, no. 6, pp. 743-749. https://doi.org/10.3109/14653241003709686
Cruz, Conrad Russell ; Hanley, Patrick J. ; Liu, Hao ; Torrano, Vicky ; Lin, Yu Feng ; Arce, James A. ; Gottschalk, Stephen ; Savoldo, Barbara ; Dotti, Gianpietro ; Louis, Chrystal U. ; Leen, Ann M. ; Gee, Adrian P. ; Rooney, Cliona M. ; Brenner, Malcolm K. ; Bollard, Catherine M. ; Heslop, Helen E. / Adverse events following infusion of T cells for adoptive immunotherapy : A 10-year experience. In: Cytotherapy. 2010 ; Vol. 12, No. 6. pp. 743-749.
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T1 - Adverse events following infusion of T cells for adoptive immunotherapy

T2 - A 10-year experience

AU - Cruz, Conrad Russell

AU - Hanley, Patrick J.

AU - Liu, Hao

AU - Torrano, Vicky

AU - Lin, Yu Feng

AU - Arce, James A.

AU - Gottschalk, Stephen

AU - Savoldo, Barbara

AU - Dotti, Gianpietro

AU - Louis, Chrystal U.

AU - Leen, Ann M.

AU - Gee, Adrian P.

AU - Rooney, Cliona M.

AU - Brenner, Malcolm K.

AU - Bollard, Catherine M.

AU - Heslop, Helen E.

PY - 2010/1/1

Y1 - 2010/1/1

N2 - Background aims. The Food and Drug Administration (FDA) currently recommends at least 4 h of recipient monitoring after T cell infusions to detect early infusion reactions. Recent catastrophic reactions to 'first-in-man' biologic agents have emphasized the importance of this rule for initial studies of new products. The value of such monitoring for better established agents is less obvious. Methods. We reviewed infusion-related adverse events (AE) following administration of ex vivo-expanded T cell products (antigen-specific cytotoxic T lymphocytes, allodepleted T cells, and genetically modified T cells) on investigational new drug (IND) studies in our center. Results. From 1998 to 2008, we infused 381 T cell products to 180 recipients, enrolled on 18 studies, receiving T cells targeting malignancies or post-transplant viral infections. There were no grade 34 infusion reactions during initial monitoring or 24-h follow-up. Twenty-four mild (grade 12) AE occurred in 21 infusions either during or immediately following infusion (up to 6 h), most commonly nausea and vomiting (10/24, 41.6%), probably because of the dimethyl sulfoxide cryoprotectant, and hypotension (20.8%), attributable to diphenhydramine pre-medication. Twenty-two additional non-severe events were reported within 24 h of infusion, most commonly culture-negative fever, chills and nausea. An increased risk of adverse events was associated with age [incidence rate ratio (IRR) 0.98; 95% confidence interval (CI) 0.961.00, P 0.05], while an increased risk of immediate infusion-related events was higher in patients reporting allergies (IRR 2.72, 95% CI 1.007.40, P 0.05); sex, disease type and T cell source (allogeneic or autologous) had no effect on frequency of adverse events. Conclusions. Infusion of these T cell products was safe in the outpatient setting and associated with no severe reactions, so monitoring for 1 h after infusion is probably sufficient. As many of the AE were attributable to diphenhydramine premedication, a lower dose (0.25 mg/kg) should be selected.

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KW - Cytotoxic T lymphocytes

KW - EpsteinBarr virus

KW - Infusion reaction

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