Prognostic significance of fluorescence intensity of surface marker expression in childhood B-precursor acute lymphoblastic leukemia. A Pediatric Oncology Group Study. Blood 1997 Jun 01;89(11):3960-6
Date
06/01/1997Pubmed ID
9166833Scopus ID
2-s2.0-0030995678 (requires institutional sign-in at Scopus site) 119 CitationsAbstract
This report describes the prognostic significance of the intensity of surface membrane antigen expression in a series of 1,231 children older than 1 year with newly diagnosed B-precursor acute lymphoblastic leukemia (ALL) treated on Pediatric Oncology Group (POG) treatment protocols. All patients had dual-color flow cytometric immunophenotyping performed at a central reference laboratory with a standard panel of monoclonal antibodies. The flow cytometers used in the study were calibrated with a standard fluorescence microparticle that permitted conversion of relative fluorescence channels to standard units of mean equivalents of soluble fluorochrome (MESF). In univariate analysis, fluorescence intensity of CD45 and CD20 was significantly associated with event-free survival (EFS), whereas other markers showed no significant correlation with outcome. Patients whose blasts were greater than the 75th percentile of intensity for CD45 (corresponding to 18,000 MESF units with CD45-FITC, or about 8% of the intensity of normal lymphocytes) fared significantly worse than those with lower-density CD45, and those whose blasts were greater than the 25th percentile of intensity for CD20 (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 expression of either antigen and traditional clinical risk factors, ploidy, 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 prognostic significance after adjusting for t(4;11). In multivariate analysis, both CD45 intensity greater than the 75th percentile and CD20 intensity greater than the 25th percentile were significantly correlated with poor outcome independently of previously reported poor prognostic factors including National Cancer Institute (NCI) risk group, ploidy, 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 information not available from simple consideration of antigen expression as positive or negative, and adds to that obtained from traditional clinical and biologic risk factors.
Author List
Borowitz MJ, Shuster J, Carroll AJ, Nash M, Look AT, Camitta B, Mahoney D, Lauer SJ, Pullen DJMESH terms used to index this publication - Major topics in bold
AdolescentAdult
Antigens, CD20
Antigens, Neoplasm
B-Lymphocytes
Biomarkers, Tumor
Child
Child, Preschool
Flow Cytometry
Fluorescence
Humans
Immunophenotyping
Infant
Leukocyte Common Antigens
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Predictive Value of Tests
Prognosis
