Prognostic testing to identify high-risk CLL

NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) and iwCLL Guidelines recommend tests such as FISH and molecular genetic testing before treatment* to inform prognostic and/or therapy determination1,2

FISH (for del 17p and del 11q)

  • FISH tests for mutations including del 17p, del 11q, del 13q, and trisomy 122
  • >80% of patients with CLL have cytogenetic lesions identifiable through FISH2
  • The iwCLL and NCCN Guidelines both recommend testing previously treated patients again before starting a new treatment1,3
    • In previously treated patients, as many as 50% have del 17p3-6
More Information

 

Molecular analysis (for IGHV)

  • >50% of patients have unmutated IGHV as identified by molecular sequence testing7
  • IGHV mutational status may not change over time8
  • This test can be done with peripheral blood9
    • Bone marrow aspirate is not necessary for IGHV testing9
More Information / Where to Test

 

DNA Sequencing (for TP53)1

  • DNA Sequencing can detect mutations of TP53

  • TP53 mutations may be observed independent of or with del 17p

  • The iwCLL and NCCN Guidelines recommend testing previously treated patients again before starting a new treatment1,3

CpG-stimulated metaphase karyotype for complex karyotype1

  • Complex Karyotype is defined as ≥3 unrelated chromosome abnormalities in more than one cell on karyotype
  • Complex karyotype is based on results of conventional karyotyping of stimulated CLL cells

A comprehensive CLL prognostic panel typically includes10:

Tests

  • ZAP-70
  • CD38+ CLL cells
  • CLL, IGHV mutation status, cell-based
  • Beta2-microglobulin, serum
  • FISH, B-cell CLL panel
  • Chromosome analysis, CLL/LPD

Methodologies

  • Culture
  • Fixed rate time nephelometry
  • Flow cytometry (FC)
  • Fluorescence in situ hybridization (FISH)
  • Karyotype
  • Polymerase chain reaction (PCR)
  • Sequencing

Flow cytometry with surrogate markers (ZAP70, CD38, CD49D) is not recommended outside the setting of a clinical trial1

*Necessary for treatment when considering chemoimmunotherapy.

CD=cluster designation, CLL=chronic lymphocytic leukemia, del=deletion, FISH=fluorescence in situ hybridization, IGHV=immunoglobulin heavy-chain variable region gene, iwCLL=International Working Group on CLL, LPD=lymphoproliferative disorder, NCCN=National Comprehensive Cancer Network.

Ordering a FISH panel

Integrating FISH testing into your CLL testing protocol

See how

References: 1. 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. 2. 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. 3. Schnaiter A, Stilgenbauer S. 17p deletion in chronic lymphocytic leukemia: risk stratification and therapeutic approach. Hematol Oncol Clin North Am. 2013;27(2):289-301. 4. Lozanski G, Heerema NA, Flinn IW, et al. Alemtuzumab is an elective therapy for chronic lymphocytic leukemia with p53 mutations and deletions. Blood. 2004;103(9):3278-3281. 5. Stilgenbauer S, Zenz T, Winkler D, et al. Subcutaneous alemtuzumab in fludarabine-refractory chronic lymphocytic leukemia: clinical results and prognostic marker analyses from the CLL2H study of the German Chronic Lymphocytic Leukemia Study Group. J Clin Oncol. 2009;27(24):3994-4001. 6. Zenz T, Häbe S, Denzel T, et al. Detailed analysis of p53 pathway defects in fludarabine-refractory chronic lymphocytic leukemia (CLL): dissecting the contribution of 17p deletion, TP53 mutation, p53-p21 dysfunction, and miR34a in a prospective clinical trial. Blood. 2009;114(13):2589-2597. 7. Zenz T, Eichhorst B, Busch R, et al. TP53 mutation and survival in chronic lymphocytic leukemia. J Clin Oncol. 2010;28(29):4473-4479. 8. Stilgenbauer S, Sander S, Bullinger L, et al. Clonal evolution in chronic lymphocytic leukemia: acquisition of high-risk genomic aberrations associated with unmutated VH, resistance to therapy, and short survival. Haematologica. 2007;92(9):1242-1245. 9. IgVH Somatic Hypermutation. https://www.labcorp.com/test-menu/29261/igvh-i-somatic-hypermutation. Accessed August 22, 2018. 10. Chronic Lymphocytic Leukemia (CLL) Prognostic Panel, Comprehensive. https://www.questdiagnostics.com/testcenter/TestDetail.action?ntc=17239. Accessed April, 3, 2019.

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