Infection Complications after Lymphodepletion and Dosing of Chimeric Antigen Receptor T (CAR-T) Cell Therapy in Patients with Relapsed/Refractory Acute Lymphoblastic Leukemia or B Cell Non-Hodgkin Lymphoma.

CAR-T cell cytokine release syndrome infection lymphodepletion

Journal

Cancers
ISSN: 2072-6694
Titre abrégé: Cancers (Basel)
Pays: Switzerland
ID NLM: 101526829

Informations de publication

Date de publication:
02 Apr 2021
Historique:
received: 15 03 2021
revised: 26 03 2021
accepted: 29 03 2021
entrez: 30 4 2021
pubmed: 1 5 2021
medline: 1 5 2021
Statut: epublish

Résumé

Chimeric antigen receptor T (CAR-T) cell therapy has proven to be very effective in patients with relapsed/refractory acute lymphoblastic leukemia (ALL) and non-Hodgkin lymphoma (NHL). However, infections-related either due to lymphodepletion or the CAR-T cell therapy itself-can result in severe and potentially life-threatening complications, while side effects such as cytokine release syndrome (CRS) might complicate differential diagnosis. Sixty-seven dosings of CAR-T cells in sixty adult patients with NHL (85%) and ALL (15%) receiving CAR-T cell therapy were assessed for infectious complications. Almost two-thirds of patients (61%) developed fever following lymphodepletion and CAR-T cell dosing. Microbiological or radiological findings were observed in 25% of all cases (bacterial 12%, viral 5%, fungal 8%). Inpatient infections were associated with more lines of therapy and more severe CRS. However, overall serious complications were rare after CAR-T therapy, with one patient dying of infection. Pathogen detection after inpatient stay was infrequent and mostly occurred in the first 90 days after dosing. Infections in CAR-T cell treated patents are common. Fast and suitable identification and treatment are crucial in these heavily pretreated and immunocompromised patients. In most cases infectious complications are manageable. Nonetheless, standardized anti-infective prophylaxis and supportive therapy are mandatory to reduce morbidity and mortality in CAR-T cell therapy.

Identifiants

pubmed: 33918340
pii: cancers13071684
doi: 10.3390/cancers13071684
pmc: PMC8038233
pii:
doi:

Types de publication

Journal Article

Langues

eng

Références

Blood. 2014 Jul 10;124(2):188-95
pubmed: 24876563
Haematologica. 2021 Apr 01;106(4):978-986
pubmed: 32327504
Bone Marrow Transplant. 2019 Oct;54(10):1643-1650
pubmed: 30809033
J Immunother Cancer. 2019 Nov 21;7(1):315
pubmed: 31753002
Clin Infect Dis. 2011 Feb 15;52(4):e56-93
pubmed: 21258094
N Engl J Med. 1993 May 6;328(18):1323-32
pubmed: 8469254
Ann Oncol. 2021 Jan;32(1):34-48
pubmed: 33098993
Clin Infect Dis. 2008 Jun 15;46(12):1813-21
pubmed: 18462102
Nat Rev Clin Oncol. 2018 Apr;15(4):218
pubmed: 29434335
Blood Adv. 2021 Jan 12;5(1):143-155
pubmed: 33570626
Clin Infect Dis. 2020 Jul 27;71(3):672-676
pubmed: 31756246
Ther Adv Hematol. 2019 Apr 15;10:2040620719841581
pubmed: 31019670
Clin Infect Dis. 2018 Aug 1;67(4):533-540
pubmed: 29481659
Blood. 2018 Jan 4;131(1):121-130
pubmed: 29038338
BMJ Open. 2019 May 19;9(5):e026644
pubmed: 31110096
N Engl J Med. 2019 Jan 3;380(1):45-56
pubmed: 30501490
Lancet Haematol. 2021 Mar;8(3):e216-e228
pubmed: 33460558
Biol Blood Marrow Transplant. 2019 Mar;25(3):e76-e85
pubmed: 30576834
Biol Blood Marrow Transplant. 2019 Jan;25(1):26-33
pubmed: 30266675
Ann Intern Med. 1972 Nov;77(5):707-14
pubmed: 4628214
Biol Blood Marrow Transplant. 2020 Jan;26(1):26-33
pubmed: 31419568
N Engl J Med. 2018 Feb 1;378(5):449-459
pubmed: 29385376
N Engl J Med. 2017 Dec 28;377(26):2531-2544
pubmed: 29226797
Haematologica. 2020 Jan 31;105(2):297-316
pubmed: 31753925
Mol Ther Methods Clin Dev. 2020 Feb 20;17:448-454
pubmed: 32201711
Cancers (Basel). 2020 Sep 30;12(10):
pubmed: 33007926

Auteurs

Felix Korell (F)

Department of Internal Medicine V-Hematology, Oncology & Rheumatology, University Hospital Heidelberg, 69120 Heidelberg, Germany.

Maria-Luisa Schubert (ML)

Department of Internal Medicine V-Hematology, Oncology & Rheumatology, University Hospital Heidelberg, 69120 Heidelberg, Germany.

Tim Sauer (T)

Department of Internal Medicine V-Hematology, Oncology & Rheumatology, University Hospital Heidelberg, 69120 Heidelberg, Germany.

Anita Schmitt (A)

Department of Internal Medicine V-Hematology, Oncology & Rheumatology, University Hospital Heidelberg, 69120 Heidelberg, Germany.

Patrick Derigs (P)

Department of Internal Medicine V-Hematology, Oncology & Rheumatology, University Hospital Heidelberg, 69120 Heidelberg, Germany.

Tim Frederik Weber (TF)

Department of Diagnostic and Interventional Radiology, University Hospital Heidelberg, 69120 Heidelberg, Germany.

Paul Schnitzler (P)

Department of Virology, University Hospital Heidelberg, 69120 Heidelberg, Germany.

Carsten Müller-Tidow (C)

Department of Internal Medicine V-Hematology, Oncology & Rheumatology, University Hospital Heidelberg, 69120 Heidelberg, Germany.

Peter Dreger (P)

Department of Internal Medicine V-Hematology, Oncology & Rheumatology, University Hospital Heidelberg, 69120 Heidelberg, Germany.

Michael Schmitt (M)

Department of Internal Medicine V-Hematology, Oncology & Rheumatology, University Hospital Heidelberg, 69120 Heidelberg, Germany.

Classifications MeSH