Clinical effect of stereotyped B-cell receptor immunoglobulins
in chronic lymphocytic leukaemia: A retrospective multicentre
study

J 2014

Clinical effect of stereotyped B-cell receptor immunoglobulins in chronic lymphocytic leukaemia: A retrospective multicentre study

BALIAKAS, P.; A. HADZIDIMITRIOU; L. A. SUTTON; E. MINGA; A. AGATHANGELIDIS et. al.

Basic information

Original name

Clinical effect of stereotyped B-cell receptor immunoglobulins in chronic lymphocytic leukaemia: A retrospective multicentre study

Authors

Edition

The Lancet. Haematology, England, 2014, 2352-3026

Other information

Language

English

Type of outcome

Article in a journal

Field of Study

30200 3.2 Clinical medicine

Country of publisher

United Kingdom of Great Britain and Northern Ireland

Confidentiality degree

is not subject to a state or trade secret

References:

URL

RIV identification code

RIV/00216224:14740/14:00079243

Organization unit

Central European Institute of Technology

DOI

https://doi.org/10.1016/S2352-3026(14)00005-2

UT WoS

000362070200008

EID Scopus

2-s2.0-84921885631

Keywords in English

B lymphocyte receptor; CD38 antigen; adolescent; adult; aged; amino acid composition; antigen expression;

Abstract

In the original language

Background: About 30% of cases of chronic lymphocytic leukaemia (CLL) carry quasi-identical B-cell receptorimmunoglobulins and can be assigned to distinct stereotyped subsets. Although preliminary evidence suggeststhat B-cell receptor immunoglobulin stereotypy is relevant from a clinical viewpoint, this aspect has never beenexplored in a systematic manner or in a cohort of adequate size that would enable clinical conclusions to be drawn.Methods: For this retrospective, multicentre study, we analysed 8593 patients with CLL for whom immunogeneticdata were available. These patients were followed up in 15 academic institutions throughout Europe (in CzechRepublic, Denmark, France, Greece, Italy, Netherlands, Sweden, and the UK) and the USA, and data were collectedbetween June 1, 2012, and June 7, 2013. We retrospectively assessed the clinical implications of CLL B-cell receptorimmunoglobulin stereotypy, with a particular focus on 14 major stereotyped subsets comprising cases expressingunmutated (U-CLL) or mutated (M-CLL) immunoglobulin heavy chain variable genes. The primary outcome ofour analysis was time to fi rst treatment, defi ned as the time between diagnosis and date of fi rst treatment.Findings: 2878 patients were assigned to a stereotyped subset, of which 1122 patients belonged to one of 14 majorsubsets. Stereotyped subsets showed signifi cant diff erences in terms of age, sex, disease burden at diagnosis,CD38 expression, and cytogenetic aberrations of prognostic signifi cance. Patients within a specifi c subset generallyfollowed the same clinical course, whereas patients in diff erent stereotyped subsets-despite having the sameimmunoglobulin heavy variable gene and displaying similar immunoglobulin mutational status-showedsubstantially diff erent times to fi rst treatment. By integrating B-cell receptor immunoglobulin stereotypy (forsubsets 1, 2, and 4) into the well established Döhner cytogenetic prognostic model, we showed these, whichcollectively account for around 7% of all cases of CLL and represent both U-CLL and M-CLL, constituted separateclinical entities, ranging from very indolent (subset 4) to aggressive disease (subsets 1 and 2).Interpretation: The molecular classifi cation of chronic lymphocytic leukaemia based on B-cell receptorimmunoglobulin stereotypy improves the Döhner hierarchical model and refi nes prognostication beyondimmunoglobulin mutational status, with potential implications for clinical decision making, especially withinprospective clinical trials.

Links

ED1.1.00/02.0068, research and development project

Name: CEITEC - central european institute of technology

EE2.3.20.0045, research and development project

Name: Podpora profesního růstu a mezinárodní integrace výzkumných týmů v oblasti molekulární medicíny

Cite

BALIAKAS, P.; A. HADZIDIMITRIOU; L. A. SUTTON; E. MINGA; A. AGATHANGELIDIS; M. NICHELATTI; A. TSANOUSA; L. SCARFÓ; Z. DAVIS; X.J. YAN; T. SHANAFELT; Karla PLEVOVÁ; Y. SANDBERG; F.J. VOJDEMAN; M. BOUDJOGRA; T. TZENOU; M. CHATZOULI; C.C. CHU; S. VERONESE; A. GARDINER; L. MANSOURI; K.E. SMEDBY; L.B. PEDERSEN; K. VAN LOM; V. GIUDECELLI; Hana SKUHROVÁ FRANCOVÁ; F. NGUYEN-KHAC; P. PANAGIOTIDIS; G. JULIUSSON; L. ANGELIS; A. ANAGNOSTOPOULOS; M.P. LEFRANC; M. FACCO; L. TRENTIN; M. CATHERWOOD; M. MONTILLO; C.H. GEISLER; A.W. LANGERAK; Šárka POSPÍŠILOVÁ; N. CHIORAZZI; D. OSCIER; D.F. JELINEK; Nikos DARZENTAS; C. BELESSI; F. DAVI; R. ROSENQUIST; P. GHIA and K. STAMATOPOULOS. Clinical effect of stereotyped B-cell receptor immunoglobulins in chronic lymphocytic leukaemia: A retrospective multicentre study. The Lancet. Haematology. England, 2014, vol. 1, No 2, p. "e74"-"e84", 11 pp. ISSN 2352-3026. Available from: https://doi.org/10.1016/S2352-3026(14)00005-2.

@article{1228043,
   author = {Baliakas, P. and Hadzidimitriou, A. and Sutton, L. A. and Minga, E. and Agathangelidis, A. and Nichelatti, M. and Tsanousa, A. and Scarfó, L. and Davis, Z. and Yan, X.J. and Shanafelt, T. and Plevová, Karla and Sandberg, Y. and Vojdeman, F.J. and Boudjogra, M. and Tzenou, T. and Chatzouli, M. and Chu, C.C. and Veronese, S. and Gardiner, A. and Mansouri, L. and Smedby, K.E. and Pedersen, L.B. and van Lom, K. and Giudecelli, V. and Skuhrová Francová, Hana and NguyenandKhac, F. and Panagiotidis, P. and Juliusson, G. and Angelis, L. and Anagnostopoulos, A. and Lefranc, M.P. and Facco, M. and Trentin, L. and Catherwood, M. and Montillo, M. and Geisler, C.H. and Langerak, A.W. and Pospíšilová, Šárka and Chiorazzi, N. and Oscier, D. and Jelinek, D.F. and Darzentas, Nikos and Belessi, C. and Davi, F. and Rosenquist, R. and Ghia, P. and Stamatopoulos, K.},
   article_location = {England},
   article_number = {2},
   doi = {https://doi.org/10.1016/S2352-3026(14)00005-2},
   keywords = {B lymphocyte receptor; CD38 antigen; adolescent; adult; aged; amino acid composition; antigen expression;},
   language = {eng},
   issn = {2352-3026},
   journal = {The Lancet. Haematology},
   title = {Clinical effect of stereotyped B-cell receptor immunoglobulins in chronic lymphocytic leukaemia: A retrospective multicentre study},
   url = {http://www.thelancet.com/pdfs/journals/lanhae/PIIS2352-3026%2814%2900005-2.pdf},
   volume = {1},
   year = {2014}
}

TY  - JOUR
ID  - 1228043
AU  - Baliakas, P. - Hadzidimitriou, A. - Sutton, L. A. - Minga, E. - Agathangelidis, A. - Nichelatti, M. - Tsanousa, A. - Scarfó, L. - Davis, Z. - Yan, X.J. - Shanafelt, T. - Plevová, Karla - Sandberg, Y. - Vojdeman, F.J. - Boudjogra, M. - Tzenou, T. - Chatzouli, M. - Chu, C.C. - Veronese, S. - Gardiner, A. - Mansouri, L. - Smedby, K.E. - Pedersen, L.B. - van Lom, K. - Giudecelli, V. - Skuhrová Francová, Hana - Nguyen-Khac, F. - Panagiotidis, P. - Juliusson, G. - Angelis, L. - Anagnostopoulos, A. - Lefranc, M.P. - Facco, M. - Trentin, L. - Catherwood, M. - Montillo, M. - Geisler, C.H. - Langerak, A.W. - Pospíšilová, Šárka - Chiorazzi, N. - Oscier, D. - Jelinek, D.F. - Darzentas, Nikos - Belessi, C. - Davi, F. - Rosenquist, R. - Ghia, P. - Stamatopoulos, K.
PY  - 2014
TI  - Clinical effect of stereotyped B-cell receptor immunoglobulins in chronic lymphocytic leukaemia: A retrospective multicentre study
JF  - The Lancet. Haematology
VL  - 1
IS  - 2
SP  - "e74"-"e84"
EP  - "e74"-"e84"
SN  - 23523026
KW  - B lymphocyte receptor
KW  - CD38 antigen
KW  - adolescent
KW  - adult
KW  - aged
KW  - amino acid composition
KW  - antigen expression;
UR  - http://www.thelancet.com/pdfs/journals/lanhae/PIIS2352-3026%2814%2900005-2.pdf
L2  - http://www.thelancet.com/pdfs/journals/lanhae/PIIS2352-3026%2814%2900005-2.pdf
N2  - Background: About 30% of cases of chronic lymphocytic leukaemia (CLL) carry quasi-identical B-cell receptorimmunoglobulins and can be assigned to distinct stereotyped subsets. Although preliminary evidence suggeststhat B-cell receptor immunoglobulin stereotypy is relevant from a clinical viewpoint, this aspect has never beenexplored in a systematic manner or in a cohort of adequate size that would enable clinical conclusions to be drawn.Methods: For this retrospective, multicentre study, we analysed 8593 patients with CLL for whom immunogeneticdata were available. These patients were followed up in 15 academic institutions throughout Europe (in CzechRepublic, Denmark, France, Greece, Italy, Netherlands, Sweden, and the UK) and the USA, and data were collectedbetween June 1, 2012, and June 7, 2013. We retrospectively assessed the clinical implications of CLL B-cell receptorimmunoglobulin stereotypy, with a particular focus on 14 major stereotyped subsets comprising cases expressingunmutated (U-CLL) or mutated (M-CLL) immunoglobulin heavy chain variable genes. The primary outcome ofour analysis was time to fi rst treatment, defi ned as the time between diagnosis and date of fi rst treatment.Findings: 2878 patients were assigned to a stereotyped subset, of which 1122 patients belonged to one of 14 majorsubsets. Stereotyped subsets showed signifi cant diff erences in terms of age, sex, disease burden at diagnosis,CD38 expression, and cytogenetic aberrations of prognostic signifi cance. Patients within a specifi c subset generallyfollowed the same clinical course, whereas patients in diff erent stereotyped subsets-despite having the sameimmunoglobulin heavy variable gene and displaying similar immunoglobulin mutational status-showedsubstantially diff erent times to fi rst treatment. By integrating B-cell receptor immunoglobulin stereotypy (forsubsets 1, 2, and 4) into the well established Döhner cytogenetic prognostic model, we showed these, whichcollectively account for around 7% of all cases of CLL and represent both U-CLL and M-CLL, constituted separateclinical entities, ranging from very indolent (subset 4) to aggressive disease (subsets 1 and 2).Interpretation: The molecular classifi cation of chronic lymphocytic leukaemia based on B-cell receptorimmunoglobulin stereotypy improves the Döhner hierarchical model and refi nes prognostication beyondimmunoglobulin mutational status, with potential implications for clinical decision making, especially withinprospective clinical trials.
ER  -

BALIAKAS, P.; A. HADZIDIMITRIOU; L. A. SUTTON; E. MINGA; A. AGATHANGELIDIS; M. NICHELATTI; A. TSANOUSA; L. SCARFÓ; Z. DAVIS; X.J. YAN; T. SHANAFELT; Karla PLEVOVÁ; Y. SANDBERG; F.J. VOJDEMAN; M. BOUDJOGRA; T. TZENOU; M. CHATZOULI; C.C. CHU; S. VERONESE; A. GARDINER; L. MANSOURI; K.E. SMEDBY; L.B. PEDERSEN; K. VAN LOM; V. GIUDECELLI; Hana SKUHROVÁ FRANCOVÁ; F. NGUYEN-KHAC; P. PANAGIOTIDIS; G. JULIUSSON; L. ANGELIS; A. ANAGNOSTOPOULOS; M.P. LEFRANC; M. FACCO; L. TRENTIN; M. CATHERWOOD; M. MONTILLO; C.H. GEISLER; A.W. LANGERAK; Šárka POSPÍŠILOVÁ; N. CHIORAZZI; D. OSCIER; D.F. JELINEK; Nikos DARZENTAS; C. BELESSI; F. DAVI; R. ROSENQUIST; P. GHIA and K. STAMATOPOULOS. Clinical effect of stereotyped B-cell receptor immunoglobulins in chronic lymphocytic leukaemia: A retrospective multicentre study. \textit{The Lancet. Haematology}. England, 2014, vol.~1, No~2, p.~''e74''-''e84'', 11 pp. ISSN~2352-3026. Available from: https://doi.org/10.1016/S2352-3026(14)00005-2.

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