Prognostic role of CD4 T-cell depletion after frontline fludarabine, cyclophosphamide and rituximab in chronic lymphocytic leukaemia.
Antineoplastic Combined Chemotherapy Protocols
/ adverse effects
CD4-Positive T-Lymphocytes
/ drug effects
Cyclophosphamide
/ adverse effects
Female
Follow-Up Studies
Humans
Immunoglobulin Variable Region
/ genetics
Immunosuppressive Agents
/ adverse effects
Leukemia, Lymphocytic, Chronic, B-Cell
/ diagnosis
Lymphocyte Count
Male
Middle Aged
Mutation
Neoplasm, Residual
Prognosis
Rituximab
/ adverse effects
Survival Analysis
Treatment Outcome
Vidarabine
/ adverse effects
CD4 T-cells
Chemo-immunotherapy
Chronic lymphocytic Leukaemia
Immunosuppression
Minimal residual disease
Journal
BMC cancer
ISSN: 1471-2407
Titre abrégé: BMC Cancer
Pays: England
ID NLM: 100967800
Informations de publication
Date de publication:
14 Aug 2019
14 Aug 2019
Historique:
received:
03
10
2018
accepted:
23
07
2019
entrez:
16
8
2019
pubmed:
16
8
2019
medline:
9
1
2020
Statut:
epublish
Résumé
Eradication of minimal residual disease (MRD), at the end of Fludarabine-Cyclophosphamide-Rituximab (FCR) treatment, is a validated surrogate marker for progression-free and overall survival in chronic lymphocytic leukaemia. But such deep responses are also associated with severe immuno-depletion, leading to infections and the development of secondary cancers. We assessed, blood MRD and normal immune cell levels at the end of treatment, in 162 first-line FCR patients, and analysed survival and adverse event. Multivariate Landmark analysis 3 months after FCR completion identified unmutated IGHV status (HR, 2.03, p = 0.043), the level of MRD reached (intermediate versus low, HR, 2.43, p = 0.002; high versus low, HR, 4.56, p = 0.002) and CD4 > 200/mm Consolidation/maintenance trials based on detectable MRD after FCR should investigate CD4 T-cell numbers both as a selection and a response criterion, and consolidation treatments should target B-cell/T-cell interactions.
Sections du résumé
BACKGROUND
BACKGROUND
Eradication of minimal residual disease (MRD), at the end of Fludarabine-Cyclophosphamide-Rituximab (FCR) treatment, is a validated surrogate marker for progression-free and overall survival in chronic lymphocytic leukaemia. But such deep responses are also associated with severe immuno-depletion, leading to infections and the development of secondary cancers.
METHODS
METHODS
We assessed, blood MRD and normal immune cell levels at the end of treatment, in 162 first-line FCR patients, and analysed survival and adverse event.
RESULTS
RESULTS
Multivariate Landmark analysis 3 months after FCR completion identified unmutated IGHV status (HR, 2.03, p = 0.043), the level of MRD reached (intermediate versus low, HR, 2.43, p = 0.002; high versus low, HR, 4.56, p = 0.002) and CD4 > 200/mm
CONCLUSIONS
CONCLUSIONS
Consolidation/maintenance trials based on detectable MRD after FCR should investigate CD4 T-cell numbers both as a selection and a response criterion, and consolidation treatments should target B-cell/T-cell interactions.
Identifiants
pubmed: 31412798
doi: 10.1186/s12885-019-5971-z
pii: 10.1186/s12885-019-5971-z
pmc: PMC6694602
doi:
Substances chimiques
Immunoglobulin Variable Region
0
Immunosuppressive Agents
0
Rituximab
4F4X42SYQ6
Cyclophosphamide
8N3DW7272P
Vidarabine
FA2DM6879K
fludarabine
P2K93U8740
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
809Références
Leukemia. 2007 May;21(5):956-64
pubmed: 17361231
Blood. 2008 Jun 15;111(12):5446-56
pubmed: 18216293
Blood. 2008 Aug 15;112(4):975-80
pubmed: 18411418
N Engl J Med. 1990 Jan 18;322(3):161-5
pubmed: 1967190
Leukemia. 2010 Jul;24(7):1310-6
pubmed: 20463751
Lancet. 2010 Oct 2;376(9747):1164-74
pubmed: 20888994
Blood. 2011 May 19;117(20):5463-72
pubmed: 21385850
J Clin Oncol. 2012 Mar 20;30(9):980-8
pubmed: 22331940
Blood. 2012 Aug 16;120(7):1412-21
pubmed: 22547582
J Clin Oncol. 2012 Sep 10;30(26):3209-16
pubmed: 22869884
Leukemia. 2013 Jan;27(1):142-9
pubmed: 23041722
Haematologica. 2013 Jan;98(1):65-70
pubmed: 23065520
Blood. 2013 May 16;121(20):4137-41
pubmed: 23493782
Blood. 2013 Oct 10;122(15):2539-49
pubmed: 23886836
N Engl J Med. 2014 Mar 20;370(12):1101-10
pubmed: 24401022
Blood. 2014 Jun 12;123(24):3727-32
pubmed: 24705492
Int J Cancer. 2014 Nov 15;135(10):2370-9
pubmed: 24723150
Blood. 2014 Oct 2;124(14):2184-9
pubmed: 25161268
Blood. 2015 Oct 15;126(16):1921-4
pubmed: 26276669
Ann Oncol. 2015 Sep;26 Suppl 5:v78-84
pubmed: 26314781
Blood. 2016 Jan 14;127(2):208-15
pubmed: 26486789
Blood. 2016 Jan 21;127(3):303-9
pubmed: 26492934
Leukemia. 2016 Apr;30(4):929-36
pubmed: 26639181
Clin Cancer Res. 2016 Apr 1;22(7):1572-82
pubmed: 26660519
Blood. 2016 Jun 16;127(24):3015-25
pubmed: 27002119
Blood. 2016 Jul 28;128(4):542-52
pubmed: 27118451
Lancet Oncol. 2016 Jul;17(7):928-942
pubmed: 27216274
J Antimicrob Chemother. 2016 Sep;71(9):2397-404
pubmed: 27550992
J Clin Oncol. 2016 Nov 1;34(31):3758-3765
pubmed: 27573660
Blood. 2016 Dec 15;128(24):2770-2773
pubmed: 27697770
Oncotarget. 2017 May 23;8(21):34661-34669
pubmed: 28416773
Hematol Oncol. 2018 Feb;36(1):128-135
pubmed: 28639416
J Clin Invest. 2017 Aug 1;127(8):3052-3064
pubmed: 28714866
Leuk Res. 2017 Sep;60:74-81
pubmed: 28759799
Haematologica. 2017 Dec;102(12):e494-e496
pubmed: 28798068
Lancet Haematol. 2017 Nov;4(11):e534-e543
pubmed: 28958469
Blood. 2017 Nov 23;130(21):2278-2282
pubmed: 29025740
J Cancer Res Clin Oncol. 2018 Mar;144(3):449-457
pubmed: 29299750
Blood. 2018 Jun 21;131(25):2745-2760
pubmed: 29540348