TY  - JOUR
A1  - Sander, Brigitta
A1  - de Jong, Daphne
A1  - Rosenwald, Andreas
A1  - Xie, Wanling
A1  - Balagué, Olga
A1  - Calaminici, Maria
A1  - Carreras, Joaquim
A1  - Gaulard, Philippe
A1  - Gribben, John
A1  - Hagenbeek, Anton
A1  - Kersten, Marie José
A1  - Molina, Thierry Jo
A1  - Lee, Abigail
A1  - Montes-Moreno, Santiago
A1  - Ott, German
A1  - Raemaekers, John
A1  - Salles, Gilles
A1  - Sehn, Laurie
A1  - Thorns, Christoph
A1  - Wahlin, Bjorn E.
A1  - Gascoyne, Randy D.
A1  - Weller, Edie
T1  - The reliability of immunohistochemical analysis of the tumor microenvironment in follicular lymphoma: a validation study from the Lunenburg Lymphoma Biomarker Consortium
JF  - Haematologica
N2  - The cellular microenvironment in follicular lymphoma is of biological and clinical importance. Studies on the clinical significance of non-malignant cell populations have generated conflicting results, which may partly be influenced by poor reproducibility in immunohistochemical marker quantification. In this study, the reproducibility of manual scoring and automated microscopy based on a tissue microarray of 25 follicular lymphomas as compared to flow cytometry is evaluated. The agreement between manual scoring and flow cytometry was moderate for CD3, low for CD4, and moderate to high for CD8, with some laboratories scoring closer to the flow cytometry results. Agreement in manual quantification across the 7 laboratories was low to moderate for CD3, CD4, CD8 and FOXP3 frequencies, moderate for CD21, low for MIB1 and CD68, and high for CD10. Manual scoring of the architectural distribution resulted in moderate agreement for CD3, CD4 and CD8, and low agreement for FOXP3 and CD68. Comparing manual scoring to automated microscopy demonstrated that manual scoring increased the variability in the low and high frequency interval with some laboratories showing a better agreement with automated scores. Manual scoring reliably identified rare architectural patterns of T-cell infiltrates. Automated microscopy analyses for T-cell markers by two different instruments were highly reproducible and provided acceptable agreement with flow cytometry. These validation results provide explanations for the heterogeneous findings on the prognostic value of the microenvironment in follicular lymphoma. We recommend a more objective measurement, such as computer-assisted scoring, in future studies of the prognostic impact of microenvironment in follicular lymphoma patients.
KW  - CD/metabolism
KW  - flow cytometry
KW  - antigens
KW  - regulatory T-cells
KW  - independent predictor
KW  - gene expression
KW  - high numbers
KW  - CD40 ligand
KW  - Riutximab
KW  - survival
KW  - marcophages
KW  - transformation
KW  - in-vitro
Y1  - 2014
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-116875
SN  - 1592-8721
VL  - 99
IS  - 4
ER  - 
TY  - JOUR
A1  - Topp, Max S.
A1  - van Meerten, Tom
A1  - Houot, Roch
A1  - Minnema, Monique C.
A1  - Bouabdallah, Krimo
A1  - Lugtenburg, Pieternella J.
A1  - Thieblemont, Catherine
A1  - Wermke, Martin
A1  - Song, Kevin W.
A1  - Avivi, Irit
A1  - Kuruvilla, John
A1  - Dührsen, Ulrich
A1  - Zheng, Yan
A1  - Vardhanabhuti, Saran
A1  - Dong, Jinghui
A1  - Bot, Adrian
A1  - Rossi, John M.
A1  - Plaks, Vicki
A1  - Sherman, Marika
A1  - Kim, Jenny J.
A1  - Kerber, Anne
A1  - Kersten, Marie José
T1  - Earlier corticosteroid use for adverse event management in patients receiving axicabtagene ciloleucel for large B-cell lymphoma
JF  - British Journal of Haematology
N2  - Axicabtagene ciloleucel (axi-cel) is an autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy approved for relapsed or refractory large B-cell lymphoma (R/R LBCL). To reduce axi-cel–related toxicity, several exploratory safety management cohorts were added to ZUMA-1 (NCT02348216), the pivotal phase 1/2 study of axi-cel in refractory LBCL. Cohort 4 evaluated the rates and severity of cytokine release syndrome (CRS) and neurologic events (NEs) with earlier corticosteroid and tocilizumab use. Primary endpoints were incidence and severity of CRS and NEs. Patients received 2 × 106 anti-CD19 CAR T cells/kg after conditioning chemotherapy. Forty-one patients received axi-cel. Incidences of any-grade CRS and NEs were 93% and 61%, respectively (grade ≥ 3, 2% and 17%). There was no grade 4 or 5 CRS or NE. Despite earlier dosing, the cumulative cortisone-equivalent corticosteroid dose in patients requiring corticosteroid therapy was lower than that reported in the pivotal ZUMA-1 cohorts. With a median follow-up of 14·8 months, objective and complete response rates were 73% and 51%, respectively, and 51% of treated patients were in ongoing response. Earlier and measured use of corticosteroids and/or tocilizumab has the potential to reduce the incidence of grade ≥ 3 CRS and NEs in patients with R/R LBCL receiving axi-cel.
KW  - toxicity
KW  - large B-cell lymphoma
KW  - axi-cel
KW  - CAR T
KW  - corticosteroids
Y1  - 2021
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-258342
VL  - 195
IS  - 3
ER  -