title: Adverse events following infusion of T cells for adoptive immunotherapy: a 10-year experience.
abstract: OBJECTIVE
  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 3-4 infusion reactions during initial monitoring or 24-h follow-up. Twenty-four mild (grade 1-2) 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) 0.96-1.00, P = 0.05], while an increased risk of immediate infusion-related events was higher in patients reporting allergies (IRR 2.72, 95% CI 1.00-7.40, 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.
authors.affiliation: Dan L Duncan Cancer Center for Cell and Gene Therapy, Baylor College of Medicine, The Methodist Hospital, Texas Children's Hospital, Houston, Texas 77030, USA.
authors.forename: Conrad Russell
authors.initials: CR
authors.lastname: Cruz
authors.forename: Patrick J
authors.initials: PJ
authors.lastname: Hanley
authors.forename: Hao
authors.initials: H
authors.lastname: Liu
authors.forename: Vicky
authors.initials: V
authors.lastname: Torrano
authors.forename: Yu-Feng
authors.initials: YF
authors.lastname: Lin
authors.forename: James A
authors.initials: JA
authors.lastname: Arce
authors.forename: Stephen
authors.initials: S
authors.lastname: Gottschalk
authors.forename: Barbara
authors.initials: B
authors.lastname: Savoldo
authors.forename: Gianpietro
authors.initials: G
authors.lastname: Dotti
authors.forename: Chrystal U
authors.initials: CU
authors.lastname: Louis
authors.forename: Ann M
authors.initials: AM
authors.lastname: Leen
authors.forename: Adrian P
authors.initials: AP
authors.lastname: Gee
authors.forename: Cliona M
authors.initials: CM
authors.lastname: Rooney
authors.forename: Malcolm K
authors.initials: MK
authors.lastname: Brenner
authors.forename: Catherine M
authors.initials: CM
authors.lastname: Bollard
authors.forename: Helen E
authors.initials: HE
authors.lastname: Heslop
mesh_terms: D000367:Age Factors; D023341:Chills; D015507:Drugs, Investigational; D005334:Fever; D005500:Follow-Up Studies; D018718:Home Infusion Therapy; D016219:Immunotherapy, Adoptive / Q000009:adverse effects*; D007262:Infusions, Intravenous; D020250:Postoperative Nausea and Vomiting / Q000209:etiology*; D013601:T-Lymphocytes / Q000378:metabolism / Q000473:pathology / Q000637:transplantation*; D014481:United States; D014486:United States Food and Drug Administration
chemical_list: D015507:Drugs, Investigational