Universität zu Köln

Jaramillo, Sonia, Agathangelidis, Andreas, Schneider, Christof, Bahlo, Jasmin, Robrecht, Sandra, Tausch, Eugen, Bloehdorn, Johannes, Hoechstetter, Manuela, Fischer, Kirsten, Eichhorst, Barbara, Goede, Valentin, Hallek, Michael, Doehner, Hartmut, Rosenquist, Richard, Ghia, Paolo, Stamatopoulos, Kostas and Stilgenbauer, Stephan (2020). Prognostic impact of prevalent chronic lymphocytic leukemia stereotyped subsets: analysis within prospective clinical trials of the German CLL Study Group. Haematologica, 105 (11). S. 2598 - 2608. PAVIA: FERRATA STORTI FOUNDATION. ISSN 0390-6078

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Abstract

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 clinico-biological 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 three phase III trials (CLL8, CLL10, CLL11), treated with different chemo-immunotherapies (n=1,861). 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 (hazard ratio [HR]: 4.2, confidence interval [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 MCLL. 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.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Jaramillo, Sonia UNSPECIFIED UNSPECIFIED UNSPECIFIED Agathangelidis, Andreas UNSPECIFIED UNSPECIFIED UNSPECIFIED Schneider, Christof UNSPECIFIED UNSPECIFIED UNSPECIFIED Bahlo, Jasmin UNSPECIFIED UNSPECIFIED UNSPECIFIED Robrecht, Sandra UNSPECIFIED UNSPECIFIED UNSPECIFIED Tausch, Eugen UNSPECIFIED UNSPECIFIED UNSPECIFIED Bloehdorn, Johannes UNSPECIFIED UNSPECIFIED UNSPECIFIED Hoechstetter, Manuela UNSPECIFIED UNSPECIFIED UNSPECIFIED Fischer, Kirsten UNSPECIFIED UNSPECIFIED UNSPECIFIED Eichhorst, Barbara UNSPECIFIED UNSPECIFIED UNSPECIFIED Goede, Valentin UNSPECIFIED UNSPECIFIED UNSPECIFIED Hallek, Michael UNSPECIFIED UNSPECIFIED UNSPECIFIED Doehner, Hartmut UNSPECIFIED UNSPECIFIED UNSPECIFIED Rosenquist, Richard UNSPECIFIED UNSPECIFIED UNSPECIFIED Ghia, Paolo UNSPECIFIED UNSPECIFIED UNSPECIFIED Stamatopoulos, Kostas UNSPECIFIED UNSPECIFIED UNSPECIFIED Stilgenbauer, Stephan UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-312525
DOI:	10.3324/haematol.2019.231027
Journal or Publication Title:	Haematologica
Volume:	105
Number:	11
Page Range:	S. 2598 - 2608
Date:	2020
Publisher:	FERRATA STORTI FOUNDATION
Place of Publication:	PAVIA
ISSN:	0390-6078
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language B-CELL RECEPTOR; CD38 EXPRESSION; GENOMIC ABERRATIONS; MUTATION STATUS; GENE-MUTATIONS; OPEN-LABEL; ANTIGEN; FLUDARABINE; IGHV3-21; SURVIVAL Multiple languages Hematology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/31252