CLONAL DIVERSITY OF IG AND T-CELL-RECEPTOR GENE REARRANGEMENTS IDENTIFIES A SUBSET OF CHILDHOOD B-PRECURSOR ACUTE LYMPHOBLASTIC-LEUKEMIA WITH INCREASED RISK OF RELAPSE

Current prognostic indicators such as age, sex, and white blood cell c ount (WBC) fail to identify all children with more aggressive forms of B-precursor acute lymphoblastic leukemia (ALL), and a proportion of p atients without poor prognostic indicators still relapse. Results obta ined from an analysis of 65 pediatic B-precursor ALL patients indicate d that subclone formation leading to clonal diversity, as detected by 1g and T-cell receptor (TCR) gene rearrangements, may represent a very useful prognostic indicator, independent of age, sex, and WBC. Diseas e-free survival was significantly shorter in those patients showing cl onal diversity at presentation. Furthermore, clonal diversify was dete cted not only in the majority of high-risk patients who relapsed but w as also associated with a high probability of relapse in standard-risk patients. sixty-five percent (13/20) of standard-risk patients who al so showed clonal diversity subsequently relapsed, whereas the percenta ge of relapses among standard-risk patients without clonal diversity w as much lower at 19% (7/36). Continued clonal evolution during disease progression is an important feature of aggressive B-precursor ALL. Al l 5 patients with clonal diversity who were followed tap in our study skewed a change in the pattern of clonality between presentation and r elapse, This implies an import ant role for clonal diversity as a mech anism of disease progression through the process of clonal variation a nd clonal selection. (C) 1998 by The American Society of Hematology.