Abstract for presentation at 11th International Congress of Human Genetics

Ploidy is an important prognostic factor in childhood acute lymphoblastic leukemia (ALL). Hyperdiploidy with >50 chromosomes (particularly those with trisomies 4,10,17,18) is associated with a favorable outcome, whereas hypodiploidy is associated with a poor outcome. The majority of hypodiploid cases have a modal number (mn) of 45 and have a significantly better outcome than those with mn <45. To further clarify the impact of hypodiploidy on outcome and to identify specific chromosomal patterns, 139 pediatric ALL cases with mn ≤44 were collected from 12 national ALL study groups or single institutions. Patients were stratified by mn into 4 groups: 24-29 (N=46); 33-39 (N=26); 40-43 (N=13) and 44 (N=54). No patients had mn 30-32. Nine patients with a t(9;22) (4 mn=44; 5 mn=43) were not considered further. Structural abnormalities were more frequent with increasing mn. Cases with 44 mn had frequent monosomies of X/Y,13,7,9,10; all 40-43 mn cases had disomies 2,6,10,11,20,22; disomies 3,7,16,17 were rare in 33-39 mn cases; and most 24-29 mn cases had disomies 21(all),X,14, or 18. There were 10 dicentrics, all in the 44 mn group. Despite a 100% remission induction rate, the event free survival (EFS) and survival for the 130 patients with hypodiploidy and no t(9;22) was 38.5% ± 4.4% and 49.8% ± at 8 years. There was no significant difference in outcome between patients with 24-29, 33-39, or 40-43 mn. Compared to patients with mn <44, patients with 44 mn had a significantly better EFS (P=.01; 8-year result, 52.2% vs 30.1%) and survival (P=.017; 69% vs 37.5%). For patients with 44 mn, monosomy 7, a dicentric chromosome, or both predicted a worse EFS but similar survival. Doubling of a hypodiploid clone occurred in 32 patients, 25 with 21-29 mn and 7 with 33-39 mn. There was no difference in outcome between patients with or without a doubled clone. Children and adolescents with hypodiploid ALL with <44 chromosomes have a poor outcome despite contemporary therapy.