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

Am J Hematol. 2019 Mar;94(3):338-345. doi: 10.1002/ajh.25385. Epub 2019 Jan 8.

Abstract

The prevalence, clinicopathologic correlates, and outcomes of previously untreated chronic lymphocytic leukemia (CLL) patients with IGH-BCL2 and IGH-BCL3 translocations are not well known. Using the Mayo Clinic CLL database, we identified patients seen between March 1, 2002 and September 30, 2016 who had FISH testing performed within 3 years of CLL diagnosis. The prognostic profile, time to first therapy (TTT), and overall survival (OS) of patients with IGH-BCL2 and IGH-BCL3 translocation were compared to patients without these abnormalities (non-IGH group). Of 1684 patients who met the inclusion criteria, 38 (2.2%) had IGH-BCL2, and 16 (0.9%) had IGH-BCL3 translocation at diagnosis. Patients with IGH-BCL3 translocation were more likely to have high and very-high CLL-International Prognostic Index, compared to patients with IGH-BCL2 translocation and the non-IGH group. The 5-year probability of requiring therapy was significantly higher for IGH-BCL3 compared to IGH-BCL2 and non-IGH groups (84% vs 33% vs 29%, respectively, P < 0.0001). The 5-year OS was significantly shorter for IGH-BCL3 compared to IGH-BCL2 and non-IGH groups (45% vs 89% vs 86%, respectively, P < 0.0001). On multivariable analyses, IGH-BCL3 translocation was associated with a shorter TTT (hazard ratio [HR] = 2.7; P = 0.005) and shorter OS (HR = 5.5; P < 0.0001); IGH-BCL2 translocation did not impact TTT and OS. In conclusion, approximately 3% of all newly diagnosed CLL patients have either an IGH-BCL2 or IGH-BCL3 translocation. Patients with IGH-BCL3 translocations have a distinct prognostic profile and outcome. These results support the inclusion of an IGH probe during the routine evaluation of FISH abnormalities in newly diagnosed CLL.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adenine / analogs & derivatives
  • Adult
  • Aged
  • Aged, 80 and over
  • Anthracyclines / therapeutic use
  • Antibodies, Monoclonal / therapeutic use
  • Antineoplastic Agents, Immunological / therapeutic use
  • B-Cell Lymphoma 3 Protein / genetics*
  • B-Cell Lymphoma 3 Protein / immunology
  • Cohort Studies
  • Female
  • Gene Expression
  • Humans
  • Immunoglobulin Heavy Chains / genetics*
  • Immunoglobulin Heavy Chains / immunology
  • Leukemia, Lymphocytic, Chronic, B-Cell / diagnosis
  • Leukemia, Lymphocytic, Chronic, B-Cell / drug therapy
  • Leukemia, Lymphocytic, Chronic, B-Cell / genetics*
  • Leukemia, Lymphocytic, Chronic, B-Cell / mortality
  • Male
  • Middle Aged
  • Oncogene Proteins, Fusion / genetics*
  • Oncogene Proteins, Fusion / immunology
  • Piperidines
  • Prognosis
  • Proto-Oncogene Proteins c-bcl-2 / genetics*
  • Proto-Oncogene Proteins c-bcl-2 / immunology
  • Pyrazoles / therapeutic use
  • Pyrimidines / therapeutic use
  • Survival Analysis
  • Translocation, Genetic
  • Treatment Outcome

Substances

  • Anthracyclines
  • Antibodies, Monoclonal
  • Antineoplastic Agents, Immunological
  • B-Cell Lymphoma 3 Protein
  • BCL2 protein, human
  • BCL3 protein, human
  • Immunoglobulin Heavy Chains
  • Oncogene Proteins, Fusion
  • Piperidines
  • Proto-Oncogene Proteins c-bcl-2
  • Pyrazoles
  • Pyrimidines
  • ibrutinib
  • Adenine