Hypodiploidy with less than 45 chromosomes confers adverse risk in childhood acute lymphoblastic leukemia: A report from the children's cancer group

We have determined the prognostic significance of hypodiploidy (<46 chromos omes) in a large cohort of children with acute lymphoblastic leukemia (ALL) treated by the Children's Cancer Group. Among 1,880 patients, 110 (5.8%) h ad hypodiploid karyotypes: 87 had 45 chromosomes, 15 had 33 to 44 chromosom es, none had 29 to 32 chromosomes, and 8 had 24 to 28 chromosomes (near-hap loidy). Six-year event-free survival (EFS) estimates for patients with 45 c hromosomes, 33 to 44 chromosomes, or 24 to 28 chromosomes were 65% (standar d deviation [SD], 8%), 40% (SD, 18%), and 25% (SD, 22%), respectively (log rank, P = .002: test for trend, P = .0009). The combined hypodiploid group had worse outcome than nonhypodiploid patients, with 6-year EFS of 58% (SD, 7%) and 76% (SD, 2%), respectively (P < .0001). EFS for the subgroup with 45 chromosomes was similar to that of patients with pseudodiploidy (P = .43 ) or 47 to 50 chromosomes (P = .76). None of the patients with 24 to 28 chr omosomes had a t(4:11), a t(9;22), or a t(1;19), and most received highly i ntensive therapy. The adverse risk associated with 33 to 44 and 24 to 28 ch romosomes remained significant in multivariate analyses adjusted for import ant risk factors including age, white blood cell count, and Philadelphia ch romosome status. Thus, hypodiploidy with less than 45 chromosomes, particul arly 24 to 28 chromosomes, is a significant adverse risk factor despite tre atment with contemporary intensive therapies. (C) 1999 by The American Soci ety of Hematology.