A simplified flow cytometric assay identifies children with acute lymphoblastic leukemia who have a superior clinical outcome.
Bone marrow normal lymphoid progenitors (CD19+, CD10+, and/or CD34+) are exquisitely sensitive to corticosteroids and other antileukemic drugs. We hypothesized that, in patients with B-lineage acute lymphoblastic leukemia (ALL), cells with this phenotype detected early in treatment should be leukemic rather than normal. We therefore developed a simple and inexpensive flow cytometric assay for such cells and prospectively applied it to bone marrow samples collected on day 19 from 380 children with B-lineage ALL. In 211 patients (55.5%), these cells represented 0.01% or more of the mononuclear cells; results correlated remarkably well with those of more complex flow cytometric and molecular minimal residual disease (MRD) evaluations. Among 84 uniformly treated children, the 10-year incidence of relapse or remission failure was 28.8% +/- 7.1% (SE) for the 42 patients with 0.01% or more leukemic cells on day 19 detected by the simplified assay versus 4.8% +/- 3.3% for the 42 patients with lower levels (P = .003). These assay results were the strongest predictor of outcome, even after adjustment for competing clinicobiologic variables. Thus, this new assay would enable most treatment centers to identify a high proportion of children with ALL who have an excellent early treatment response and a high likelihood of cure.
Coustan-Smith
Elaine
E
Department of Hematology-Oncology, and International Outreach Progrm, St Jude Children's Research Hospital, Memphis, TN 38105, USA.
Ribeiro
Raul C
RC
Stow
Patricia
P
Zhou
Yinmei
Y
Pui
Ching-Hon
CH
Rivera
Gaston K
GK
Pedrosa
Francisco
F
Campana
Dario
D
D018941:Antigens, CD19 / Q000096:biosynthesis; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D002051:Burkitt Lymphoma / Q000175:diagnosis* / Q000188:drug therapy / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D005260:Female; D005434:Flow Cytometry / Q000379:methods*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008214:Lymphocytes / Q000378:metabolism; D008297:Male; D018365:Neoplasm, Residual / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics; D010641:Phenotype; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000175:diagnosis* / Q000188:drug therapy / Q000235:genetics; D011379:Prognosis; D012008:Recurrence; D012074:Remission Induction; D012680:Sensitivity and Specificity; D016896:Treatment Outcome
D018941:Antigens, CD19