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Immunoglobulin Gene Sequence Analysis In Chronic Lymphocytic Leukemia: From Patient Material To Sequence Interpretation
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Immunoglobulin Gene Sequence Analysis In Chronic Lymphocytic Leukemia: From Patient Material To Sequence Interpretation

Published on: November 26, 2018

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IGH translocations in chronic lymphocytic leukemia: Clinicopathologic features and clinical outcomes

Hong Fang1, Kaaren K Reichard1, Kari G Rabe2

  • 1Division of Hematopathology, Mayo Clinic, Rochester, Minnesota.

American Journal of Hematology
|December 22, 2018
PubMed

Insights

Chronic lymphocytic leukemia (CLL) patients with IGH-BCL3 translocations face a poorer prognosis, requiring earlier therapy and shorter overall survival. IGH-BCL2 translocations did not significantly impact outcomes, supporting routine FISH testing for IGH abnormalities in newly diagnosed CLL.

Area of Science:

  • Hematology
  • Oncology
  • Genetics

Background:

  • The prognostic significance of IGH-BCL2 and IGH-BCL3 translocations in previously untreated chronic lymphocytic leukemia (CLL) is not well-defined.
  • Understanding these genetic abnormalities is crucial for accurate prognostication and treatment planning.

Purpose of the Study:

  • To determine the prevalence, clinicopathologic correlates, and outcomes of CLL patients with IGH-BCL2 and IGH-BCL3 translocations.
  • To compare the prognostic profile, time to first therapy (TTT), and overall survival (OS) of patients with these translocations versus those without.

Main Methods:

  • Retrospective analysis of 1684 CLL patients diagnosed between March 2002 and September 2016 from the Mayo Clinic CLL database.
  • FISH testing was performed within 3 years of diagnosis.
  • Comparison of TTT and OS between patients with IGH-BCL2, IGH-BCL3 translocations, and a non-IGH group.

Main Results:

  • IGH-BCL2 and IGH-BCL3 translocations were identified in 2.2% and 0.9% of patients, respectively.
  • Patients with IGH-BCL3 translocation showed higher CLL-International Prognostic Index scores, significantly higher 5-year probability of requiring therapy (84% vs 33% vs 29%), and shorter 5-year OS (45% vs 89% vs 86%) compared to IGH-BCL2 and non-IGH groups.
  • Multivariable analysis confirmed IGH-BCL3 translocation as a predictor of shorter TTT (HR=2.7) and OS (HR=5.5), while IGH-BCL2 had no significant impact.

Conclusions:

  • Approximately 3% of newly diagnosed CLL patients harbor IGH-BCL2 or IGH-BCL3 translocations.
  • IGH-BCL3 translocation is associated with a distinct, unfavorable prognostic profile and outcome in CLL.
  • Routine FISH evaluation for IGH probes in newly diagnosed CLL is recommended to identify high-risk patients.

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