Comparison of the biology of Down syndrome (DS) acute lymphoblastic leukemia (ALL) and non-DS ALL: Children's Oncology Group (COG) study P9900.

10003 Background: DS ALL is a heterogeneous disorder with inferior survival compared to non-DS. Controversy exists regarding the relative frequencies of sentinel cytogenetic lesions in children with DS and ALL. METHODS: COG P9900 was a laboratory classification study for ALL therapeutic trials from 12/99 to 2/05. Flow cytometry for DNA index; molecular testing for TEL-AML1, E2A-PBX1, BCR-ABL and FISH testing for trisomies 4 and 10 and for MLL rearrangements were done centrally for risk group stratification in a prospective manner to assign continuing treatment. RESULTS: Eighty of 2811 (3%) consecutively enrolled eligible B-precursor ALL patients (pts) had DS. Age > or < than 10 years of age, gender, presenting white blood cell count (WBC) and NCI risk group were similar between ALL patients with/without DS. However, the genetic lesions present in DS-ALL patients and the event-free survival (EFS) and overall survival (OS) differed from those of non-DS patients. No BCR/ABL or MLL translocations were found in the DS pts. TEL-AML1 fusion was present in 2.5% (2/80) of DS-ALL pts vs. 24% (651/2710) (p<0.0001) of non-DS-ALL pts. Trisomies of chromosomes 4 and 10 were present in 7.7% (6/78) of DS-ALL pts vs. 24% (643/2689) (p=0.0004) of non-DS-ALL pts. Five-year EFS and OS were inferior in pts with DS-ALL; 70% vs. 76% (p=0.078), and 86% vs. 90% (p=0.0333). However, when pts with MLL, BCR/ABL, TEL-AML 1 and trisomies 4 and 10 were excluded, the EFS and OS for both groups were equivalent with EFS for DS 68% vs. 70% for non-DS (p=0.8174), and OS for DS 87% vs. 85% for non-DS (p=0.8519). CONCLUSIONS: The inferior outcome of patients with ALL and DS is related to a much lower incidence of favorable genetic features (TEL- AML 1 and trisomies of chromosomes 4 and 10). Further investigation into the distinct pathogenesis of DS ALL is warranted to improve treatment response. No significant financial relationships to disclose.

Duke Scholars

Author Paul Langlie Martin Pediatrics, Transplant and Cellular Therapy