PROGNOSTIC-SIGNIFICANCE OF FLUORESCENCE INTENSITY OF SURFACE MARKER EXPRESSION IN CHILDHOOD B-PRECURSOR ACUTE LYMPHOBLASTIC-LEUKEMIA - A PEDIATRIC-ONCOLOGY-GROUP STUDY

This report describes the prognostic significance of the intensity of surface membrane antigen expression in a series of 1,231 children olde r than 1 year with newly diagnosed B-precursor acute lymphoblastic leu kemia (ALL) treated on Pediatric Oncology Group (FOG) treatment protoc ols. All patients had dual-color flow cytometric immunophenotyping per formed at a central reference laboratory with a standard panel of mono clonal antibodies. The flow cytometers used in the study were calibrat ed with a standard fluorescence microparticle that permitted conversio n of relative fluorescence channels to standard units of mean equivale nts of soluble fluorochrome (MESF). In univariate analysis, fluorescen ce intensity of CD45 and CD20 was significantly associated with event- free survival (EFS), whereas other markers showed no significant corre lation with outcome. Patients whose blasts were greater than the 75th percentile of intensity for CD45 (corresponding to 18,000 MESF units w ith CD45-FITC, or about 8% of the intensity of normal lymphocytes) far ed significantly worse than those with lower-density CD45, and those w hose blasts were greater than the 25th percentile of intensity for CD2 0 (corresponding to 17,900 MESF units with CD20-PE) had a poorer EFS. The intensity of both CD45 and CD20 was independently correlated with outcome. There was no significant correlation between intensity of exp ression of either antigen and traditional clinical risk factors, ploid y, or t(9;22) or t(1;19). All patients with t(4;11) had CD45 intensity greater than the 75th percentile, but CD45 intensity retained its pro gnostic significance after adjusting for t(4; 11). In multivariate ana lysis, both CD45 intensity greater than the 75th percentile and CD20 i ntensity greater than the 25th percentile were significantly correlate d with poor outcome independently of previously reported poor prognost ic factors including National Cancer Institute (NCI) risk group, ploid y, trisomies of 4 and 10, and adverse translocations including t(1;19) , t(9;22), and t(4; 11). We conclude that in childhood B-precursor ALL , the intensity of expression of CD20 and CD45 provides prognostic inf ormation not available from simple consideration of antigen expression as positive or negative, and adds to that obtained from traditional c linical and biologic risk factors. (C) 1997 by The American Society of Hematology.