Cytogenetic studies of infant acute lymphoblastic leukemia: poor prognosis of infants with t(4;11) – a report of the Children’s Cancer Group

Abstract

Infants less than 1 year of age at diagnosis of acute lymphoblastic leukemia (ALL) have a poor prognosis, which has been attributed primarily to a breakpoint in chromosomal band 11q23 or the MLL gene. Most infants with an 11q23 breakpoint have a t(4;11)(q21;q23). We studied the cytogenetics of the leukemia cells of 56 infants on CCG-1883, a single-arm clinical treatment protocol for infant ALL. Twenty-one patients had t(4;11)(q21;q23), seven had other rearrangements with breakpoints in 11q23 (other 11q23), 16 had normal chromosomes, two had t(1;19)(q32;p13), one had >50 chromosomes, and nine had non-recurring structural abnormalities. To determine whether there is a difference in outcome for infants with t(4;11), other 11q23 and the remaining patients, we compared event-free survival (EFS) and other clinical and laboratory features of the above infants. Infants without t(4;11) and those with other 11q23 rearrangements had significantly better EFS than those with t(4;11) (P = 0.007 and P = 0.02, respectively). t(4;11) correlated with age less than 6 months and with CD10 negativity, both of which also were poor prognostic indicators. After adjustment for age, there was still a significant difference in EFS between patients with t(4;11) and those with other 11q23 rearrangements (P = 0.02), and between patients with t(4;11) and those without t(4;11) (P = 0.04). Among CD10 negative patients, t(4;11) was associated with a worse EFS (P = 0.01). Multivariate analysis showed that after adjusting for a variety of clinical and laboratory features, t(4;11) was the most important prognostic factor for poor outcome, and patients with other 11q23 rearrangements had as good an outcome as the remaining patients without t(4;11).