Immunoglobulin Heavy Chain Translocation Probe Improves CLL Risk Stratification

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(ChemotherapyAdvisor) – Testing for immunoglobulin heavy chain translocations (t(IGH@)) improves risk stratification for patients with chronic lymphocytic leukemia (CLL)-associated deletion 13q (del13q), according to a single-institution study published in Cancer Genetics

“(I)n this cohort, the presence of a t(IGH@) negatively impacted the TFS [treatment free survival] and OS [overall survival] of patients with del13, further stratifying this large and heterogeneous subgroup into two separate prognostic entities,” reported lead author Alina Gerrie, MD, Division of Hematology, University of British Columbia, Vancouver, Canada, and coauthors.

“Importantly, the outcomes of CLL patients with del13q and a coexistent t(IGH@) were similar to those of patients with intermediate and unfavorable cytogenetics,” they noted. “This may explain part of the clinical heterogeneity seen in del13q patients and lends further support to include an IGH@ probe in routine FISH analysis.”

Patients with both del13q and a t(IGH@) suffered significantly worse TFS than patients with del13q but not a t(IGH@) (median TFS 4.7 vs. 8.0 years, P=0.03), a relationship that remained statistically significant in multivariate analysis after data was adjusted for patient age, sex, Rai stage, and white blood cell count (hazard ratio [HR]=4.21, 95% confidence interval, 1.06-16.69, P=0.04).

t(IGH@) translocations involving chromosome 14q32 are increasingly recognized as being associated with poor prognosis in CLL patients, but little has previously been published about t(IGH@)'s impact on prognosis when it occurs in association with recurrent cytogenetic abnormalities in patients with CLL, detected with fluorescence in situ hybridization (FISH).

Studies of a larger patient population are needed to validate this study's results, the authors cautioned.

“Knowledge of the t(IGH@) status in CLL is therefore of clinical importance, as del13q patients with concomitant t(IGH@) may not retain the previously expected favorable outcome,” the authors concluded.


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