Factors affecting lymphocyte collection efficiency for the manufacture of chimeric antigen receptor T cells in adults with B-cell malignancies.
Adult
Aged
B-Lymphocytes
/ metabolism
Blood Component Removal
Cell- and Tissue-Based Therapy
/ methods
Female
Humans
Lymphocytes
/ cytology
Male
Middle Aged
Precursor Cell Lymphoblastic Leukemia-Lymphoma
/ metabolism
Receptors, Chimeric Antigen
/ metabolism
Retrospective Studies
Risk Factors
Young Adult
Journal
Transfusion
ISSN: 1537-2995
Titre abrégé: Transfusion
Pays: United States
ID NLM: 0417360
Informations de publication
Date de publication:
05 2019
05 2019
Historique:
received:
18
10
2018
revised:
21
12
2018
accepted:
21
12
2018
pubmed:
8
2
2019
medline:
2
6
2020
entrez:
8
2
2019
Statut:
ppublish
Résumé
The clinical and procedural parameters that affect the optimal collection of lymphocytes for the production of chimeric antigen receptor (CAR) T cells remain undefined but are increasingly important, as commercial products are now available. We evaluated determinants of low lymphocyte collection efficiency (CE) and the rate of successful CAR T-cell manufacture in middle-aged and older adults with advanced B-cell malignancies. Mononuclear cell collections using two apheresis platforms (COBE Spectra and Spectra Optia, Terumo BCT) from patients participating in a CD19-directed CAR T-cell therapy trial were reviewed. Patient- and disease-specific factors, peripheral blood counts, apheresis parameters, and product cell counts were analyzed to determine effects on lymphocyte CE. Ninety-two apheresis events from patients with acute lymphocytic leukemia (ALL) (n = 28), chronic lymphocytic leukemia (n = 18), and non-Hodgkin lymphoma (n = 46) were available for analysis. Forty-one collections (45%) had a lymphocyte CE of <40%. On multivariable analysis, age (every 10-year increase, odds ratio [OR] = 1.51; p = 0.034), disease type (chronic lymphocytic leukemia vs. ALL, OR = 0.24; p = 0.052; non-Hodgkin lymphoma vs. ALL, OR = 0.20; p = 0.009) and precollection platelets (every 10 × 10 Lymphocyte collection at our center was well tolerated and 100% successful in manufacturing CD19-directed CAR T cells from adult patients with B-cell malignancies despite low CE in some patients. A diagnosis of ALL, advancing age, and higher preapheresis platelet counts were observed to be associated with low CE.
Sections du résumé
BACKGROUND
The clinical and procedural parameters that affect the optimal collection of lymphocytes for the production of chimeric antigen receptor (CAR) T cells remain undefined but are increasingly important, as commercial products are now available. We evaluated determinants of low lymphocyte collection efficiency (CE) and the rate of successful CAR T-cell manufacture in middle-aged and older adults with advanced B-cell malignancies.
STUDY DESIGNS AND METHODS
Mononuclear cell collections using two apheresis platforms (COBE Spectra and Spectra Optia, Terumo BCT) from patients participating in a CD19-directed CAR T-cell therapy trial were reviewed. Patient- and disease-specific factors, peripheral blood counts, apheresis parameters, and product cell counts were analyzed to determine effects on lymphocyte CE.
RESULTS
Ninety-two apheresis events from patients with acute lymphocytic leukemia (ALL) (n = 28), chronic lymphocytic leukemia (n = 18), and non-Hodgkin lymphoma (n = 46) were available for analysis. Forty-one collections (45%) had a lymphocyte CE of <40%. On multivariable analysis, age (every 10-year increase, odds ratio [OR] = 1.51; p = 0.034), disease type (chronic lymphocytic leukemia vs. ALL, OR = 0.24; p = 0.052; non-Hodgkin lymphoma vs. ALL, OR = 0.20; p = 0.009) and precollection platelets (every 10 × 10
CONCLUSIONS
Lymphocyte collection at our center was well tolerated and 100% successful in manufacturing CD19-directed CAR T cells from adult patients with B-cell malignancies despite low CE in some patients. A diagnosis of ALL, advancing age, and higher preapheresis platelet counts were observed to be associated with low CE.
Identifiants
pubmed: 30729531
doi: 10.1111/trf.15178
pmc: PMC6499685
mid: NIHMS1018946
doi:
Substances chimiques
Receptors, Chimeric Antigen
0
Banques de données
ClinicalTrials.gov
['NCT01865617']
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1773-1780Subventions
Organisme : NHLBI NIH HHS
ID : T32 HL007093
Pays : United States
Organisme : NIH HHS
ID : P30 CA015704
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA015704
Pays : United States
Organisme : NCI NIH HHS
ID : T32CA009515
Pays : United States
Organisme : NCI NIH HHS
ID : T32 CA009515
Pays : United States
Organisme : NHLBI NIH HHS
ID : T32HL007093
Pays : United States
Informations de copyright
© 2019 AABB.
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