Correlation of CD33 expression level with disease characteristics and response to gemtuzumab ozogamicin containing chemotherapy in childhood AML.

Publication Type:

Journal Article

Source:

Blood, Volume 119, Issue 16, p.3705-11 (2012)

Keywords:

2012, Center-Authored Paper, Clinical Research Division, Genomics Core Facility, Mar 2012, March 2012, Shared Resources

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 monoclonal antibody. CD33 mean fluorescent intensity (MFI) of leukemic blasts was prospectively quantified in 619 de novo pediatric AML patients enrolled on Children's Oncology Group GO-containing clinical trials and correlated with disease characteristics and clinical outcome. CD33 expression varied over 2-log fold; a median MFI of 129 (range 3-1550.07) was observed. Patients were divided into 4 quartiles (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<0.001) and inversely associated with low-risk disease (P<0.001). CR rates were similar but patients in Q4 had significantly lower OS (57%+/-16% versus 77%+/- 7%, P= 0.002) and DFS from CR (44% +/- 16% versus 62% +/- 8%, P= 0.022). In a multivariate model, high CD33 expression remained a significant predictor of OS (P=0.011) and DFS (P=0.038) 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. Correlation of CD33 expression with GO response is under investigation. The studies are registered at www.ClinicalTrials.gov as NCT00070174 and NCT00372593.