Rituximab induces rapid blood repopulation by CLL cells
mediated through their release from immune niches and
complement exhaustion

J 2021

Rituximab induces rapid blood repopulation by CLL cells mediated through their release from immune niches and complement exhaustion

BORSKÝ, Marek, Viera HRABČÁKOVÁ, Jitka NOVOTNÁ, Yvona BRYCHTOVÁ, Michael DOUBEK et. al.

Basic information

Original name

Rituximab induces rapid blood repopulation by CLL cells mediated through their release from immune niches and complement exhaustion

Authors

BORSKÝ, Marek (203 Czech Republic, belonging to the institution), Viera HRABČÁKOVÁ (703 Slovakia, belonging to the institution), Jitka NOVOTNÁ (203 Czech Republic, belonging to the institution), Yvona BRYCHTOVÁ (203 Czech Republic, belonging to the institution), Michael DOUBEK (203 Czech Republic, belonging to the institution), Anna PANOVSKÁ (203 Czech Republic, belonging to the institution), Petr MULLER (203 Czech Republic), Jiří MAYER (203 Czech Republic, belonging to the institution), Martin TRBUŠEK (203 Czech Republic, guarantor, belonging to the institution) and Marek MRÁZ (203 Czech Republic, belonging to the institution)

Edition

Leukemia Research, OXFORD, PERGAMON-ELSEVIER SCIENCE LTD, 2021, 0145-2126

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

30205 Hematology

Country of publisher

United Kingdom of Great Britain and Northern Ireland

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

URL

Impact factor

Impact factor: 3.715

RIV identification code

RIV/00216224:14110/21:00124279

Organization unit

Faculty of Medicine

DOI

http://dx.doi.org/10.1016/j.leukres.2021.106684

UT WoS

000703570900003

Keywords in English

Chronic lymphocytic leukemia/CLL; Rituximab; Complement; Recrudescence; Peripheral blood repopulation

Abstract

V originále

The in vivo rituximab effects in B cell malignancies are only partially understood. Here we analyzed in a large chronic lymphocytic leukemia (CLL) cohort (n = 80) the inter-patient variability in CLL cell count reduction within the first 24 h of rituximab administration in vivo, and a phenomenon of blood repopulation by malignant cells after anti-CD20 antibody therapy. Larger CLL cell elimination after rituximab infusion was associated with lower pre-therapy CLL cell counts, higher CD20 levels, and the non-exhausted capacity of complement dependent cytotoxicity (CDC). The absolute amount of cell-surface CD20 molecules (CD20 density x CLL lymphocytosis) was a predictor for complement exhaustion during therapy. We also describe that a highly variable decrease in CLL cell counts at 5 h (88 %-2%) following rituximab infusion is accompanied in most patients by peripheral blood repopulation with CLL cells at 24 h, and in similar to 20 % of patients, this resulted in CLL counts higher than before therapy. We provide evidence that CLL cells recrudescence is linked with i) CDC exhaustion, which leads to the formation of an insufficient amount of membrane attack complexes, likely resulting in temporary retention of surviving rituximab-opsonized cells by the mononuclear-phagocyte system (followed by their release back to blood), and ii) CLL cells regression from immune niches (CXCR4(dim)CD5(bright) intraclonal subpopulation). Patients with major peripheral blood CLL cell repopulation exhibited a longer time to-progression after chemoimmunotherapy compared to patients with lower or no repopulation, suggesting chemotherapy vulnerability of CLL cells that repopulate the blood.

Citovat

BORSKÝ, Marek, Viera HRABČÁKOVÁ, Jitka NOVOTNÁ, Yvona BRYCHTOVÁ, Michael DOUBEK, Anna PANOVSKÁ, Petr MULLER, Jiří MAYER, Martin TRBUŠEK and Marek MRÁZ. Rituximab induces rapid blood repopulation by CLL cells mediated through their release from immune niches and complement exhaustion. Leukemia Research. OXFORD: PERGAMON-ELSEVIER SCIENCE LTD, 2021, vol. 111, December 2021, p. 1-11. ISSN 0145-2126. Available from: https://dx.doi.org/10.1016/j.leukres.2021.106684.

@article{1836826,
   author = {Borský, Marek and Hrabčáková, Viera and Novotná, Jitka and Brychtová, Yvona and Doubek, Michael and Panovská, Anna and Muller, Petr and Mayer, Jiří and Trbušek, Martin and Mráz, Marek},
   article_location = {OXFORD},
   article_number = {December 2021},
   doi = {http://dx.doi.org/10.1016/j.leukres.2021.106684},
   keywords = {Chronic lymphocytic leukemia/CLL; Rituximab; Complement; Recrudescence; Peripheral blood repopulation},
   language = {eng},
   issn = {0145-2126},
   journal = {Leukemia Research},
   title = {Rituximab induces rapid blood repopulation by CLL cells mediated through their release from immune niches and complement exhaustion},
   url = {https://www.sciencedirect.com/science/article/pii/S0145212621001855?via%3Dihub},
   volume = {111},
   year = {2021}
}

TY  - JOUR
ID  - 1836826
AU  - Borský, Marek - Hrabčáková, Viera - Novotná, Jitka - Brychtová, Yvona - Doubek, Michael - Panovská, Anna - Muller, Petr - Mayer, Jiří - Trbušek, Martin - Mráz, Marek
PY  - 2021
TI  - Rituximab induces rapid blood repopulation by CLL cells mediated through their release from immune niches and complement exhaustion
JF  - Leukemia Research
VL  - 111
IS  - December 2021
SP  - 1-11
EP  - 1-11
PB  - PERGAMON-ELSEVIER SCIENCE LTD
SN  - 01452126
KW  - Chronic lymphocytic leukemia/CLL
KW  - Rituximab
KW  - Complement
KW  - Recrudescence
KW  - Peripheral blood repopulation
UR  - https://www.sciencedirect.com/science/article/pii/S0145212621001855?via%3Dihub
N2  - The in vivo rituximab effects in B cell malignancies are only partially understood. Here we analyzed in a large chronic lymphocytic leukemia (CLL) cohort (n = 80) the inter-patient variability in CLL cell count reduction within the first 24 h of rituximab administration in vivo, and a phenomenon of blood repopulation by malignant cells after anti-CD20 antibody therapy. Larger CLL cell elimination after rituximab infusion was associated with lower pre-therapy CLL cell counts, higher CD20 levels, and the non-exhausted capacity of complement dependent cytotoxicity (CDC). The absolute amount of cell-surface CD20 molecules (CD20 density x CLL lymphocytosis) was a predictor for complement exhaustion during therapy. We also describe that a highly variable decrease in CLL cell counts at 5 h (88 %-2%) following rituximab infusion is accompanied in most patients by peripheral blood repopulation with CLL cells at 24 h, and in similar to 20 % of patients, this resulted in CLL counts higher than before therapy. We provide evidence that CLL cells recrudescence is linked with i) CDC exhaustion, which leads to the formation of an insufficient amount of membrane attack complexes, likely resulting in temporary retention of surviving rituximab-opsonized cells by the mononuclear-phagocyte system (followed by their release back to blood), and ii) CLL cells regression from immune niches (CXCR4(dim)CD5(bright) intraclonal subpopulation). Patients with major peripheral blood CLL cell repopulation exhibited a longer time to-progression after chemoimmunotherapy compared to patients with lower or no repopulation, suggesting chemotherapy vulnerability of CLL cells that repopulate the blood.
ER  -

BORSKÝ, Marek, Viera HRABČÁKOVÁ, Jitka NOVOTNÁ, Yvona BRYCHTOVÁ, Michael DOUBEK, Anna PANOVSKÁ, Petr MULLER, Jiří MAYER, Martin TRBUŠEK and Marek MRÁZ. Rituximab induces rapid blood repopulation by CLL cells mediated through their release from immune niches and complement exhaustion. \textit{Leukemia Research}. OXFORD: PERGAMON-ELSEVIER SCIENCE LTD, 2021, vol.~111, December 2021, p.~1-11. ISSN~0145-2126. Available from: https://dx.doi.org/10.1016/j.leukres.2021.106684.

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