CD33-Negative Acute Myeloid Leukemia (AML) Has Similar Characteristics to CD33-Positive Disease.

Abstract 4129

Several immunophenotypic subgroups within AML are associated with specific disease characteristics, e.g., CD19-positive AML is associated with t(8;21)(q22;q22) and CD56 expression is associated with adverse outcome. CD33 is a sialic acid-binding immunoglobulin-like lectin (Siglec) located on chromosome 19q13.3. It is highly expressed on early multilineage hematopoietic progenitors but absent from the pluripotent hematopoietic stem cells. It contains two tyrosine phosphorylation motifs whose phosphorylation depends on Src and is the target of gemtuzumab ozogamicin. We asked if lack of CD33 expression (<10%) on the surface of AML blasts was associated with different disease characteristics. We identified 15 such newly diagnosed AML cases and compared their characteristics with 45 (1:3 ratio) cases matched by age and French-American-British subtypes (only cases with M0, M1 and M2 were included). The mean white blood cell count at diagnosis (18.3 ×10⁹/L, 41.7×10⁹/L; p=0.149) and percent of secondary AML [either antecedent hematologic disorder (13%, 18%; p=1) or therapy-related (7%, 16%; p=0.6657)] among the CD33-negative group was similar to the CD33-positive cohort. The percent of unknown (21%, 19%), intermediate (64%, 51%) and unfavorable (14%, 30%) karyotype (p=0.5484) and the percent of cases with FLT3 (20%, 18%; p=0.6058) and NPM1 (7%, 22%; p=0.1562) was also similar among the CD33-negative and the CD33-positive cohorts. The patients were treated with available protocols. There was no significant difference between CD33-negative and CD33-positive treatment assignment. A total of 50% of the CD33-negative cases achieved complete remission compared to 48% of the CD33-positive cases. The median overall survival was 17.1 [95% confidence interval (CI) 10.3, 22.5] versus 10.6 (95% CI 7.1, 16.9) months (p=0.7488) for the CD33-negative compared with the CD33-positive cases. Finally, disease-free survival was also similar between the two groups; 11.0 (95% CI 6.2, 22.6) months for the CD33-negative cohort versus 9.5 (95% CI 4.5, 118.2) months for the CD33-positive group (p=0.966). In summary, CD33 expression does not alter disease characteristics and does not appear to affect outcome in AML unless treatment with gemtuzumab ozogamicin is considered.