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

• Published in: American journal of hematology Vol. 94; no. 3; pp. 338 - 345
• Main Authors: Fang, Hong, Reichard, Kaaren K., Rabe, Kari G., Hanson, Curtis A., Call, Timothy G., Ding, Wei, Kenderian, Saad S., Muchtar, Eli, Schwager, Susan M., Leis, Jose F., Chanan‐Khan, Asher A., Slager, Susan L., Braggio, Esteban, Smoley, Stephanie A., Kay, Neil E., Shanafelt, Tait D., Van Dyke, Daniel L., Parikh, Sameer A.
• Format: Journal Article
• Language: English
• Published: Hoboken, USA John Wiley & Sons, Inc 01.03.2019; Wiley Subscription Services, Inc
• Subjects: 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; Chronic lymphocytic leukemia; Clinical outcomes; Cohort Studies; Diagnosis; Female; Gene Expression; Heavy chains; Hematology; Humans; Immunoglobulin Heavy Chains - genetics; Immunoglobulin Heavy Chains - immunology; Immunoglobulins; Leukemia; 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; Lymphatic leukemia; 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; Translocation, Genetic; Treatment Outcome
• ISSN: 0361-8609; 1096-8652; 1096-8652
• DOI: 10.1002/ajh.25385

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.