IGH@ Translocations Are Prevalent in Teenagers and Young Adults With Acute Lymphoblastic Leukemia
In a study reported in the Journal of Clinical Oncology, Russell et al found that immunoglobulin heavy chain (IGH@) translocations were present in a substantial proportion of younger patients with acute lymphoblastic leukemia (ALL), including those with B-cell precursor ALL. However, IGH@ translocation was not found to be an independent prognostic factor in younger patients.
In the study, high-throughput fluorescent in situ hybridization was used to detect IGH@ translocations in 3,269 patients with ALL treated in either the UKALL2003 trial for children and adolescents (aged 1 to 24 years) or the UKALLXII trial for adolescents and adults (aged 15 to 59 years).
Prevalence
IGH@ translocations were found in 159 patients (5%), including both those with B-cell disease (148 of 2863 = 5.1%) and those with T-cell disease (11 of 408 = 2.7%). Multiple partner genes were identified, including CRLF2 (n = 35), five members of the CEPB gene family (n = 17), and ID4 (n = 11). The level of the IGH@-positive clone varied, with some translocations being primary events and others being secondary events that were often associated with additional established aberrations. IGH@ translocation showed a distinct age profile, occurring at a median age of 16 years and having a peak incidence of 11% among patients aged 20 to 24 years.
Not Independent Predictor in Younger Patients
Among patients with B-cell precursor ALL who were Philadelphia chromosome negative, those with IGH@ translocation had poorer overall survival in both the UKALL2003 population (hazard ratio [HR] = 2.37, P = .003) and the UKALLXII population (HR = 1.73, P = .002) on univariate analysis. However, on multivariate analysis including age, white blood cell count, minimal residual disease status, and sex, IGH@ translocation was not associated with significant differences in event-free survival (HR = 1.03, P = .9), relapse-free survival (HR = 0.91, P = .82), or overall survival (HR = 0.95, P= .9). There was no difference in the outcome among patients with IGH@ translocation according to CRLF2 status.
Poorer Outcome in Older Patients
As had been reported previously by the investigators, IGH@ translocation in patients with B-cell precursor Philadelphia chromosome-negative ALL in the UKALLXII study was associated with significantly poorer event-free survival (HR = 1.54, P < .01) and overall survival (HR = 1.64, P = .006) on multivariate analysis. However, as they noted, these differences appear to have been related to an increased risk of first remission death, since translocation was not associated with a significantly greater relapse risk (HR = 1.35, P =.21, for relapse-free survival). There was no difference in outcome among patients with IGH@ translocation according to CRLF2 status.
The investigators concluded, “IGH@ translocations define a genetic feature that is frequent among adolescents and young adults with ALL. Although associated with an adverse outcome in adults, it is not an independent prognostic factor in children and adolescents.”
Lisa J. Russell, PhD, of the Royal Victoria Infirmary, Newcastle-upon-Tyne, is the corresponding author for the Journal of Clinical Oncology article.
The study was supported by the Kay Kendall Leukemia Fund and Leukemia & Lymphoma Research. Study author Karl S. Laczko reported an employment or leadership position with Leica Microsystems.
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