PMID- 33131249
OWN - NLM
STAT- MEDLINE
DCOM- 20210427
LR  - 20230926
IS  - 1592-8721 (Electronic)
IS  - 0390-6078 (Print)
IS  - 0390-6078 (Linking)
VI  - 105
IP  - 11
DP  - 2020 Nov 1
TI  - Prognostic impact of prevalent chronic lymphocytic leukemia stereotyped subsets: 
      analysis within prospective clinical trials of the German CLL Study Group 
      (GCLLSG).
PG  - 2598-2607
LID - 10.3324/haematol.2019.231027 [doi]
AB  - Almost one-third of all patients with chronic lymphocytic leukemia (CLL) express 
      stereotyped B cell receptor immunoglobulins (BcR IG) and can be assigned to 
      distinct subsets, each with a particular BcR IG. The largest stereotyped subsets 
      are #1, #2, #4 and #8, associated with specific clinicobiological characteristics 
      and outcomes in retrospective studies. We assessed the associations and 
      prognostic value of these BcR IG in prospective multicenter clinical trials 
      reflective of two different clinical situations: i) early-stage patients 
      (watch-and-wait arm of the CLL1 trial) (n=592); ii) patients in need of 
      treatment, enrolled in 3 phase III trials (CLL8, CLL10, CLL11), treated with 
      different chemo-immunotherapies (n=1861). Subset #1 was associated with del(11q), 
      higher CLL international prognostic index (CLL-IPI) scores and similar clinical 
      course to CLL with unmutated immunoglobulin heavy variable (IGHV) genes (U-CLL) 
      in both early and advanced stage groups. IGHV-mutated (M-CLL) subset #2 cases had 
      shorter time-to-first-treatment (TTFT) versus other M-CLL cases in the 
      early-stage cohort (HR: 4.2, CI: 2-8.6, p<0.001), and shorter 
      time-to-next-treatment (TTNT) in the advanced-stage cohort (HR: 2, CI: 1.2-3.3, 
      p=0.005). M-CLL subset #4 was associated with lower CLL-IPI scores and younger 
      age at diagnosis; in both cohorts, these patients showed a trend towards better 
      outcomes versus other M-CLL. U-CLL subset #8 was associated with trisomy 12. 
      Overall, this study shows that major stereotyped subsets have distinctive 
      characteristics. For the first time in prospective multicenter clinical trials, 
      subset # 2 appeared as an independent prognostic factor for earlier TTFT and TTNT 
      and should be proposed for risk stratification of patients.
FAU - Jaramillo, Sonia
AU  - Jaramillo S
AD  - Department of Internal Medicine III, Ulm University, Ulm, Germany.
FAU - Agathangelidis, Andreas
AU  - Agathangelidis A
AD  - Institute of Applied Biosciences, Centre for Research and Technology, 
      Thessaloniki, Greece.
FAU - Schneider, Christof
AU  - Schneider C
AD  - Department of Internal Medicine III, Ulm University, Ulm, Germany.
FAU - Bahlo, Jasmin
AU  - Bahlo J
AD  - Dept I of Internal Medicine and Center of Integrated Oncology Cologne Bonn, 
      Cologne, Germany.
FAU - Robrecht, Sandra
AU  - Robrecht S
AD  - Dept I of Internal Medicine and Center of Integrated Oncology Cologne Bonn, 
      Cologne, Germany.
FAU - Tausch, Eugen
AU  - Tausch E
AD  - Department of Internal Medicine III, Ulm University, Ulm, Germany.
FAU - Bloehdorn, Johannes
AU  - Bloehdorn J
AD  - Department of Internal Medicine III, Ulm University, Ulm, Germany.
FAU - Hoechstetter, Manuela
AU  - Hoechstetter M
AD  - Department of Hematology, Oncology, Munchen Klinik Schwabing, Munich, Germany.
FAU - Fischer, Kirsten
AU  - Fischer K
AD  - Dept I of Internal Medicine and Center of Integrated Oncology Cologne Bonn, 
      Cologne, Germany.
FAU - Eichhorst, Barbara
AU  - Eichhorst B
AD  - Dept I of Internal Medicine and Center of Integrated Oncology Cologne Bonn, 
      Cologne, Germany.
FAU - Goede, Valentin
AU  - Goede V
AD  - Dept I of Internal Medicine and Center of Integrated Oncology Cologne Bonn, 
      Cologne, Germany.
FAU - Hallek, Michael
AU  - Hallek M
AD  - Dept I of Internal Medicine and Center of Integrated Oncology Cologne Bonn, 
      Cologne, Germany.
FAU - Dohner, Hartmut
AU  - Dohner H
AD  - Department of Internal Medicine III, Ulm University, Ulm, Germany.
FAU - Rosenquist, Richard
AU  - Rosenquist R
AD  - Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, 
      Sweden.
FAU - Ghia, Paolo
AU  - Ghia P
AD  - Universita Vita-Salute San Raffaele and IRCCS Ospedale San Raffaele, Milan, 
      Italy.
FAU - Stamatopoulos, Kostas
AU  - Stamatopoulos K
AD  - Institute of Applied Biosciences, Centre for Research and Technology, 
      Thessaloniki, Greece.
FAU - Stilgenbauer, Stephan
AU  - Stilgenbauer S
AD  - Department of Internal Medicine III, Ulm University, Ulm, Germany.
LA  - eng
SI  - ClinicalTrials.gov/NCT00262782
SI  - ClinicalTrials.gov/NCT00281918
SI  - ClinicalTrials.gov/NCT01010061
PT  - Journal Article
PT  - Multicenter Study
PT  - Research Support, Non-U.S. Gov't
DEP - 20201101
PL  - Italy
TA  - Haematologica
JT  - Haematologica
JID - 0417435
RN  - 0 (Immunoglobulin Heavy Chains)
SB  - IM
MH  - Humans
MH  - Immunoglobulin Heavy Chains/genetics
MH  - *Leukemia, Lymphocytic, Chronic, B-Cell/diagnosis/drug therapy/epidemiology
MH  - Mutation
MH  - Prognosis
MH  - Prospective Studies
MH  - Retrospective Studies
PMC - PMC7604575
EDAT- 2020/11/03 06:00
MHDA- 2021/04/28 06:00
PMCR- 2019/12/26
CRDT- 2020/11/02 04:21
PHST- 2019/12/26 00:00 [aheadofprint]
PHST- 2020/11/02 04:21 [entrez]
PHST- 2020/11/03 06:00 [pubmed]
PHST- 2021/04/28 06:00 [medline]
PHST- 2019/12/26 00:00 [pmc-release]
AID - 10.3324/haematol.2019.231027 [doi]
PST - epublish
SO  - Haematologica. 2020 Nov 1;105(11):2598-2607. doi: 10.3324/haematol.2019.231027.