The majority of CLL patients have some genetic abnormality1,2

3 important factors associated with poor prognosis1,3

  • Unmutated IGHV
  • Del 17p and TP53 mutations
  • Del 11q

 

Most common chromosomal aberrations associated with favorable/neutral prognosis1

  • Del 13q

  • Trisomy 12

 

Other biomarkers that may provide prognostic information6,12

  • CD38
  • CD49d
  • ZAP-70
  • NOTCH1 Gene Mutations
  • SF3B1 Gene Mutations
  • BIRC3 Gene Mutations

 

Complex Karyotype

  • Complex Karyotype may be defined as ≥3 unrelated chromosomal abnormalities in more than one cell on CpG-stimulated karyotype of CLL cells6
  • Stimulated metaphase karyotyping shows that leukemia cells with a complex karyotype (ie, ≥3 chromosomal abnormalities) may have adverse prognostic significance7

Testing according to guidelines can identify biomarkers implicated in poor outcomes2,4-11

Del 17p, which is present in ≤10% of treatment-naïve CLL patients, is associated with poor response and shorter median survival in patients when treated with chemotherapy or chemoimmunotherapy.5-9

Del 11q, which is present in ~20% of patients with CLL, is associated with extensive lymphadenopathy, disease progression, and shorter median survival.6,7,10

Unmutated IGHV, which is present in >50% of patients, is associated with atypical morphology of B cells, aggressive disease, and decreased survival.2,11

CD=cluster designation, CLL=chronic lymphocytic leukemia, Del=deletion, IGHV=immunoglobulin heavy-chain variable region gene.

Importance of IGHV mutational status

Testing for IGHV mutation can inform prognosis and treatment determination in CLL.

See how

References: 1. Döhner H, Stilgenbauer S, Benner A, et al. Genomic aberrations and survival in chronic lymphocytic leukemia. N Engl J Med. 2000;343(26):1910-1916. 2. Kröber A, Seiler T, Benner A, et al. VH mutation status, CD38 expression level, genomic aberrations, and survival in chronic lymphocytic leukemia. Blood. 2002;100(4):1410-1416. 3. Hallek M, Cheson BD, Catovsky D, et al. iwCLL guidelines for diagnosis, indications for treatment, response assessment, and supportive management of CLL. Blood. 2018;131(25):2745-2760. 4. Grever MR, Lucas DM, Dewald GW, et al. Comprehensive assessment of genetic and molecular features predicting outcome in patients with chronic lymphocytic leukemia: results from the US Intergroup Phase III Trial E2997. J Clin Oncol. 2007;25(7):799-804. 5. Döhner H, Stilgenbauer S, James MR, et al. 11q deletions identify a new subset of B-cell chronic lymphocytic leukemia characterized by extensive nodal involvement and inferior prognosis. Blood. 1997;89(7):2516-2522. 6. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma V.4.2019. © National Comprehensive Cancer Network, Inc. 2019. All rights reserved. Accessed April 15, 2019. To view the most recent and complete version of the guideline, go online to NCCN.org.  7. Hallek M, Cheson BD, Catovsky D, et al. iwCLL guidelines for diagnosis, indications for treatment, response assessment, and supportive management of CLL. Blood. 2018;131(25):2745-2760. 8. Stilgenbauer S, Kröber A, Busch R, et al. 17p deletion predicts for inferior overall survival after fludarabine-based first line therapy in chronic lymphocytic leukemia: first analysis of genetics in the CLL4 trial of the GCLLSG. Blood (ASH Annual Meeting Abstracts). 2005;106(11):Abstract 715. 9. Stilgenbauer S, Zenz T, Winkler D, et al. Genomic aberrations, VH mutation status and outcome after fludarabine and cyclophosphamide (FC) or FC plus rituximab (FCR) in the CLL8 trial. Presented at: 50th Annual ASH Meeting; December 6-9, 2008; San Francisco, CA. Abstract 781. 10. Parker TL, Strout MP. Chronic lymphocytic leukemia: prognostic factors and impact on treatment. Discov Med. 2011;11(57):115-123. 11. Hamblin TJ, Davis Z, Gardiner A, Oscier DG, Stevenson FK. Unmutated Ig VH genes are associated with a more aggressive form of chronic lymphocytic leukemia. Blood. 1999;94(6):1848-1854. 12. Leukemia & Lymphoma Society. Chronic Lymphocytic Leukemia. https://www.lls.org/sites/default/files/file_assets/PS34_CLL_Booklet_2017_9_7FINAL.pdf. Revised 2017. Accessed March 7, 2019.

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