title: Correlation of CD33 expression level with disease characteristics and response to gemtuzumab ozogamicin containing chemotherapy in childhood AML.
abstract: CD33 is expressed on the majority of acute myeloid leukemia (AML) leukemic blasts and is the target for gemtuzumab ozogamicin (GO), a toxin-conjugated anti-CD33 mAb. In the present study, we quantified the CD33 mean fluorescent intensity of leukemic blasts prospectively in 619 de novo pediatric AML patients enrolled in Children's Oncology Group GO-containing clinical trials and determined its correlation with disease characteristics and clinical outcome. CD33 expression varied more than 2-log fold; a median mean fluorescent intensity of 129 (range, 3-1550.07) was observed. Patients were divided into 4 quartiles, quartiles 1-4 (Q1-4) based on expression and disease characteristics and clinical response defined across quartiles. High CD33 expression was associated with high-risk FLT3/ITD mutations (P < .001) and was inversely associated with low-risk disease (P < .001). Complete remission (CR) rates were similar, but patients in Q4 had significantly lower overall survival (57% ± 16% vs 77% ± 7%, P = .002) and disease-free survival from CR (44% ± 16% vs 62% ± 8%, P = .022). In a multivariate model, high CD33 expression remained a significant predictor of overall survival (P = .011) and disease-free survival (P = .038) from CR. Our findings suggest that CD33 expression is heterogeneous within de novo pediatric AML. High expression is associated with adverse disease features and is an independent predictor of inferior outcome. The correlation between CD33 expression and GO response is under investigation. These studies are registered at www.clinicaltrials.gov as NCT00070174 and NCT00372593.
authors.affiliation: Fred Hutchinson Cancer Research Center, Seattle, WA, USA. jessica.pollard@seattlechildrens.org
authors.forename: Jessica A
authors.initials: JA
authors.lastname: Pollard
authors.forename: Todd A
authors.initials: TA
authors.lastname: Alonzo
authors.forename: Michael
authors.initials: M
authors.lastname: Loken
authors.forename: Robert B
authors.initials: RB
authors.lastname: Gerbing
authors.forename: Phoenix A
authors.initials: PA
authors.lastname: Ho
authors.forename: Irwin D
authors.initials: ID
authors.lastname: Bernstein
authors.forename: Susana C
authors.initials: SC
authors.lastname: Raimondi
authors.forename: Betsy
authors.initials: B
authors.lastname: Hirsch
authors.forename: Janet
authors.initials: J
authors.lastname: Franklin
authors.forename: Roland B
authors.initials: RB
authors.lastname: Walter
authors.forename: Alan
authors.initials: A
authors.lastname: Gamis
authors.forename: Soheil
authors.initials: S
authors.lastname: Meshinchi
mesh_terms: D000617:Aminoglycosides / Q000008:administration & dosage*; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage*; D015703:Antigens, CD / Q000276:immunology / Q000378:metabolism*; D015214:Antigens, Differentiation, Myelomonocytic / Q000276:immunology / Q000378:metabolism*; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D002648:Child; D002675:Child, Preschool; D016903:Drug Monitoring / Q000379:methods; D005260:Female; D000079982:Gemtuzumab; D006801:Humans; D007223:Infant; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy* / Q000453:epidemiology / Q000276:immunology; D008297:Male; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012307:Risk Factors; D063268:Sialic Acid Binding Ig-like Lectin 3; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000617:Aminoglycosides; D061067:Antibodies, Monoclonal, Humanized; D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D000970:Antineoplastic Agents; C571163:CD33 protein, human; D063268:Sialic Acid Binding Ig-like Lectin 3; D000079982:Gemtuzumab