PMID- 36440594
OWN - NLM
STAT- MEDLINE
DCOM- 20230405
LR  - 20230409
IS  - 2045-7634 (Electronic)
IS  - 2045-7634 (Linking)
VI  - 12
IP  - 6
DP  - 2023 Mar
TI  - A comprehensive assessment of lymphocyte subsets, their prognostic significance, 
      and changes after first-line therapy administration in patients with chronic 
      lymphocytic leukemia.
PG  - 6956-6970
LID - 10.1002/cam4.5492 [doi]
AB  - BACKGROUND: In chronic lymphocytic leukemia (CLL), changes in the peripheral 
      blood lymphocyte subsets play an important role in disease progression and 
      infectious complications. The impact of chemoimmunotherapy (CIT) on these changes 
      has not been extensively studied METHODS: We used multi-color flow cytometry, to 
      prospectively measure absolute and relative numbers of CD4(+) and CD8(+) T-cells 
      and their subsets in 45 patients with indolent untreated CLL, 86 patients 
      indicated for first-line treatment, and 34 healthy controls. In 55 patients, we 
      analyzed the impact of CIT RESULTS: CLL patients had a significant increase in 
      most cell populations in comparison to controls. Progression of CLL was 
      characterized by significantly elevated counts with the exception of a lower 
      percentage of naive T-cells. After treatment, the percentage of naive T-cells 
      further decreased at the expense of effector memory T-cells (TEM). In patients 
      with indolent CLL, higher percentages of naive CD4(+) (p = 0.0026) and naive 
      CD8(+) (p = 0.023) T-cells were associated with a longer time to first treatment 
      (TTFT). The elevation of CD4(+) central memory T-cells (TCM) (p = 0.27) and TEM 
      (p = 0.003) counts and a higher percentage of CD4(+) TEM (p = 0.0047), were 
      linked with shorter TTFT. In treated patients, increased regulatory T-cells count 
      was associated with shorter time to next treatment (TTNT) (p = 0.042), while 
      higher CD4(+) TCM count with shorter TTNT (p = 0.035) and shorter overall 
      survival (p = 0.041). CONCLUSION: Our results indicate that naive cell depletion 
      and CD4(+) TCM and TEM increases are detrimental to CLL patients' prognosis.
CI  - (c) 2022 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.
FAU - Vodarek, Pavel
AU  - Vodarek P
AUID- ORCID: 0000-0002-8050-7594
AD  - 4th Department of Internal Medicine - Hematology, Faculty of Medicine, University 
      Hospital and Charles University, Hradec Kralove, Czech Republic.
FAU - Ecsiova, Dominika
AU  - Ecsiova D
AUID- ORCID: 0000-0002-6897-8756
AD  - 4th Department of Internal Medicine - Hematology, Faculty of Medicine, University 
      Hospital and Charles University, Hradec Kralove, Czech Republic.
FAU - Rezacova, Vladimira
AU  - Rezacova V
AUID- ORCID: 0000-0001-5802-1371
AD  - Institute of Clinical Immunology and Allergology, Faculty of Medicine, University 
      Hospital and Charles University, Hradec Kralove, Czech Republic.
FAU - Soucek, Ondrej
AU  - Soucek O
AUID- ORCID: 0000-0003-3137-4200
AD  - Institute of Clinical Immunology and Allergology, Faculty of Medicine, University 
      Hospital and Charles University, Hradec Kralove, Czech Republic.
FAU - Simkovic, Martin
AU  - Simkovic M
AUID- ORCID: 0000-0003-0331-5334
AD  - 4th Department of Internal Medicine - Hematology, Faculty of Medicine, University 
      Hospital and Charles University, Hradec Kralove, Czech Republic.
FAU - Vokurkova, Doris
AU  - Vokurkova D
AUID- ORCID: 0000-0001-6979-2825
AD  - Institute of Clinical Immunology and Allergology, Faculty of Medicine, University 
      Hospital and Charles University, Hradec Kralove, Czech Republic.
FAU - Belada, David
AU  - Belada D
AUID- ORCID: 0000-0002-4981-6188
AD  - 4th Department of Internal Medicine - Hematology, Faculty of Medicine, University 
      Hospital and Charles University, Hradec Kralove, Czech Republic.
FAU - Zak, Pavel
AU  - Zak P
AUID- ORCID: 0000-0003-4465-5343
AD  - 4th Department of Internal Medicine - Hematology, Faculty of Medicine, University 
      Hospital and Charles University, Hradec Kralove, Czech Republic.
FAU - Smolej, Lukas
AU  - Smolej L
AUID- ORCID: 0000-0002-4187-8595
AD  - 4th Department of Internal Medicine - Hematology, Faculty of Medicine, University 
      Hospital and Charles University, Hradec Kralove, Czech Republic.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20221128
PL  - United States
TA  - Cancer Med
JT  - Cancer medicine
JID - 101595310
SB  - IM
MH  - Humans
MH  - *Leukemia, Lymphocytic, Chronic, B-Cell
MH  - Prognosis
MH  - CD8-Positive T-Lymphocytes
MH  - Lymphocyte Subsets
MH  - T-Lymphocytes, Regulatory
MH  - T-Lymphocyte Subsets
MH  - CD4-Positive T-Lymphocytes
PMC - PMC10067047
OTO - NOTNLM
OT  - CLL
OT  - chemoimmunotherapy
OT  - immunosuppression
OT  - infections
OT  - lymphocyte subset
OT  - prognosis
COIS- Pavel Vodarek reports consultations for Roche, Gilead, Janssen-Cilag and Servier, 
      research funding from Roche, honoraria and travel grants from AbbVie, Roche, 
      Gilead, Janssen-Cilag, Servier, and Celgene. Martin Simkovic reports consultancy 
      fees, advisory board participation fees, travel grants, and honoraria from 
      Janssen-Cilag, Gilead, Roche, AstraZeneca, and AbbVie. David Belada reports 
      consultancy fees, advisory board participation fees, travel grants and honoraria 
      from Roche, Takeda, Gilead, and Janssen Cilag. Lukas Smolej reports honoraria, 
      consultancy fees and travel grants from Roche, AbbVie, Janssen, and AstraZeneca. 
      Other authors report no conflicts of interest.
EDAT- 2022/11/29 06:00
MHDA- 2023/04/05 06:42
PMCR- 2022/11/28
CRDT- 2022/11/28 05:13
PHST- 2022/10/03 00:00 [revised]
PHST- 2022/07/27 00:00 [received]
PHST- 2022/11/18 00:00 [accepted]
PHST- 2023/04/05 06:42 [medline]
PHST- 2022/11/29 06:00 [pubmed]
PHST- 2022/11/28 05:13 [entrez]
PHST- 2022/11/28 00:00 [pmc-release]
AID - CAM45492 [pii]
AID - 10.1002/cam4.5492 [doi]
PST - ppublish
SO  - Cancer Med. 2023 Mar;12(6):6956-6970. doi: 10.1002/cam4.5492. Epub 2022 Nov 28.