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

Infants less than 1 year of age at diagnosis of acute lymphoblastic leukemi a (ALL) have a poor prognosis, which has been attributed primarily to a bre akpoint in chromosomal band 11q23 or the MLL gene. Most infants with an 11q 23 breakpoint have a t(4;11)(q21;q23). We studied the cytogenetics of the l eukemia cells of 56 infants on CCG-1883, a single-arm clinical treatment pr otocol 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 h ad non-recurring structural abnormalities. To determine whether there is a difference in outcome for infants with t(4;11), other 11q23 and the remaini ng patients, we compared event-free survival (EFS) and other clinical and l aboratory features of the above infants. Infants without 1(4;11) and those with other 11q23 rearrangements had significantly better EFS than those wit h t(4;11) (P = 0.007 and P = 0.02, respectively), t(4;11) correlated with a ge less than 6 months and with CD10 negativity, both of which also were poo r prognostic indicators. After adjustment for age, there was still a signif icant 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 thos e without t(4;11) (P = 0.04). Among CD10 negative patients, t(4;11) was ass ociated with a worse EFS (P = 0.01). Multivariate analysis showed that afte r adjusting for a variety of clinical and laboratory features, t(4;11) was the most important prognostic factor for poor outcome, and patients with ot her 11q23 rearrangements had as good an outcome as the remaining patients w ithout t(4;11).