Prevalence and prognostic significance of chromosome 21 amplifications in children with relapsed acute lymphoblastic leukemia: the ALL-REZ BFM study group

Survival after relapse of childhood ALL is currently predicted from clinical factors; however, the underlying molecular determinants are poorly understood. To identify chromosomal alterations associated with prognosis, we screened 223 patients with first relapse of B-cell precursor ALL by multiplex ligation-dependent probe amplification (MLPA). Gains of chromosome 21 (chr21) were the most frequent alterations (41%) that were further classified into 3 groups: gain of chr21 (+21, 15%), gain of chr21 and a pattern of additional gains consistent with high hyperdiploidy (+21/HHD, 21%) as well as intrachromosomal amplification (iAMP21, 5%). Concerning time of relapse, all 3 groups had less early relapses than patients without an amplification of chr21. iAMP21 patients showed entirely late relapses. All 3 groups had a significant higher rate of treatment related death. The cumulative incidence of relapses was higher in patients with +21 or iAMP21 than in +21/HHD patients indicating that HHD positively influences outcome. Collectively, our results show that chr21 amplifications are the most frequent chromosomal alterations in relapsed ALL and are associated with prognosis and outcome.