PMID- 36127509
OWN - NLM
STAT- MEDLINE
DCOM- 20221031
LR  - 20230502
IS  - 1476-5551 (Electronic)
IS  - 0887-6924 (Print)
IS  - 0887-6924 (Linking)
VI  - 36
IP  - 11
DP  - 2022 Nov
TI  - Impact of conditioning chemotherapy on lymphocyte kinetics and outcomes in LBCL 
      patients treated with CAR T-cell therapy.
PG  - 2669-2677
LID - 10.1038/s41375-022-01704-z [doi]
AB  - Conditioning chemotherapy (CCT) has been shown to be essential for optimal 
      efficacy of chimeric antigen receptor (CAR) T-cell therapy. Here, we determined 
      whether the change in absolute lymphocyte count, referred to as delta lymphocyte 
      index (DLIx), may serve as a surrogate marker for pharmacodynamic effects of CCT 
      and whether it associated with germline genetic variants in patients with large 
      B-cell lymphoma (LBCL). One-hundred and seventy-one patients were included, of 
      which 86 (50%) received bridging therapy post-leukapheresis. Median DLIx was 
      0.5 x 10(9)/L (range, 0.01-2.75 x 10(9)/L) and was significantly higher in 
      patients who achieved complete response (p = 0.04). On multivariate analysis, low 
      DLIx was associated only with use of bridging therapy (odds ratio 0.4, 95% CI 
      0.2-0.8, p = 0.007). Low DLIx was independently associated with shorter 
      progression-free (p = 0.02) and overall survival (p = 0.02). DLIx was associated 
      with genetic variations related to drug metabolism and macrophage biology such as 
      ABCB1, MISP and CPVL. The impact of CCT on lymphocyte count is affected by use of 
      bridging therapy but change in lymphocyte count is independently associated with 
      efficacy. Studies aimed at investigating macrophage biology in this setting may 
      suggest strategies to increase the efficacy of CCT and improve outcomes.
CI  - (c) 2022. The Author(s), under exclusive licence to Springer Nature Limited.
FAU - Strati, Paolo
AU  - Strati P
AUID- ORCID: 0000-0002-7445-1459
AD  - Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer 
      Center, Houston, TX, USA. pstrati@mdanderson.org.
AD  - Department of Translational Molecular Pathology, The University of Texas MD 
      Anderson Cancer Center, Houston, TX, USA. pstrati@mdanderson.org.
FAU - Jallouk, Andrew P
AU  - Jallouk AP
AD  - Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer 
      Center, Houston, TX, USA.
FAU - Sun, Ryan
AU  - Sun R
AD  - Department of Biostatistics, The University of Texas MD Anderson Cancer Center, 
      Houston, TX, USA.
FAU - Choi, Jaihee
AU  - Choi J
AD  - Department of Biostatistics, The University of Texas MD Anderson Cancer Center, 
      Houston, TX, USA.
FAU - Das, Kaberi
AU  - Das K
AUID- ORCID: 0000-0003-4702-0386
AD  - Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer 
      Center, Houston, TX, USA.
FAU - Cherng, Hua-Jay
AU  - Cherng HJ
AD  - Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer 
      Center, Houston, TX, USA.
FAU - Ahmed, Sairah
AU  - Ahmed S
AUID- ORCID: 0000-0001-7302-8299
AD  - Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer 
      Center, Houston, TX, USA.
FAU - Lee, Hun J
AU  - Lee HJ
AD  - Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer 
      Center, Houston, TX, USA.
FAU - Iyer, Swaminathan P
AU  - Iyer SP
AD  - Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer 
      Center, Houston, TX, USA.
FAU - Nair, Ranjit
AU  - Nair R
AD  - Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer 
      Center, Houston, TX, USA.
FAU - Nastoupil, Loretta J
AU  - Nastoupil LJ
AUID- ORCID: 0000-0001-6071-8610
AD  - Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer 
      Center, Houston, TX, USA.
FAU - Steiner, Raphael E
AU  - Steiner RE
AUID- ORCID: 0000-0003-3717-3629
AD  - Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer 
      Center, Houston, TX, USA.
FAU - Huff, Chad D
AU  - Huff CD
AD  - Department of Epidemiolog, The University of Texas MD Anderson Cancer Center, 
      Houston, TX, USA.
FAU - Yu, Yao
AU  - Yu Y
AD  - Department of Epidemiolog, The University of Texas MD Anderson Cancer Center, 
      Houston, TX, USA.
FAU - Mistry, Haleigh
AU  - Mistry H
AD  - Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer 
      Center, Houston, TX, USA.
FAU - Pulsifer, Brittany
AU  - Pulsifer B
AD  - Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer 
      Center, Houston, TX, USA.
FAU - Noorani, Mansoor
AU  - Noorani M
AD  - Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer 
      Center, Houston, TX, USA.
FAU - Saini, Neeraj
AU  - Saini N
AD  - Department of Stem Cell Transplantation and Cellular Therapy, The University of 
      Texas MD Anderson Cancer Center, Houston, TX, USA.
FAU - Shpall, Elizabeth J
AU  - Shpall EJ
AD  - Department of Stem Cell Transplantation and Cellular Therapy, The University of 
      Texas MD Anderson Cancer Center, Houston, TX, USA.
FAU - Kebriaei, Partow
AU  - Kebriaei P
AUID- ORCID: 0000-0002-8607-9404
AD  - Department of Stem Cell Transplantation and Cellular Therapy, The University of 
      Texas MD Anderson Cancer Center, Houston, TX, USA.
FAU - Flowers, Christopher R
AU  - Flowers CR
AUID- ORCID: 0000-0002-9524-3990
AD  - Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer 
      Center, Houston, TX, USA.
FAU - Westin, Jason R
AU  - Westin JR
AD  - Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer 
      Center, Houston, TX, USA.
FAU - Hildebrandt, Michelle A T
AU  - Hildebrandt MAT
AD  - Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer 
      Center, Houston, TX, USA.
FAU - Neelapu, Sattva S
AU  - Neelapu SS
AUID- ORCID: 0000-0003-1045-4914
AD  - Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer 
      Center, Houston, TX, USA.
LA  - eng
GR  - P30 CA016672/CA/NCI NIH HHS/United States
GR  - R21 CA259694/CA/NCI NIH HHS/United States
GR  - T32 CA009666/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20220920
PL  - England
TA  - Leukemia
JT  - Leukemia
JID - 8704895
RN  - 0 (Antigens, CD19)
SB  - IM
MH  - Humans
MH  - *Immunotherapy, Adoptive/adverse effects
MH  - Antigens, CD19
MH  - Neoplasm Recurrence, Local/drug therapy
MH  - Leukapheresis
MH  - Lymphocytes/pathology
MH  - *Lymphoma, Large B-Cell, Diffuse/pathology
PMC - PMC9904360
MID - NIHMS1869227
EDAT- 2022/09/21 06:00
MHDA- 2022/11/01 06:00
PMCR- 2023/05/01
CRDT- 2022/09/20 23:31
PHST- 2022/02/08 00:00 [received]
PHST- 2022/09/09 00:00 [accepted]
PHST- 2022/09/05 00:00 [revised]
PHST- 2022/09/21 06:00 [pubmed]
PHST- 2022/11/01 06:00 [medline]
PHST- 2022/09/20 23:31 [entrez]
PHST- 2023/05/01 00:00 [pmc-release]
AID - 10.1038/s41375-022-01704-z [pii]
AID - 10.1038/s41375-022-01704-z [doi]
PST - ppublish
SO  - Leukemia. 2022 Nov;36(11):2669-2677. doi: 10.1038/s41375-022-01704-z. Epub 2022 
      Sep 20.