Pediatric acute myeloid leukemia (AML) affects approximately 5-10% of patients who suffer from refractory disease, resulting in a relapse rate of 20-35%, with an overall survival (OS) rate of just 40%. Traditional chemotherapy regimens can’t be intensified as this would increase Treatment-Related Mortality (TRM). Therefore, targeted and less toxic therapies such as Gemtuzumab ozogamicin (GO) are necessary to improve the survival rates of pediatric AML patients. GO is a monoclonal antibody (CD33-directed) linked to the cytotoxic agent calicheamicin, and it holds potential due to the widespread CD33 expression in 85-90% of AML blasts. Though initially approved by the United States Food and Drug Administration (US FDA) in 2000, GO was voluntarily withdrawn in 2010 by the company. GO was later re-approved and evaluated in clinical trials such as the ALFA-0701 trial and the Children’s Oncology Group (COG) AAML0531 trial, which led to the FDA’s approval for pediatric patients aged 1 month or older. In this article, we review the clinical outcomes of different dosages of GO, administered at different time points during treatment, in the treatment of de novo pediatric AML. We highlight the optimal dose and time points for administering GO while discussing potential predictors of response, including CD33 expression, CD33 single-nucleotide polymorphisms (SNPs), the PgP-1 drug efflux transporter, and Annexin A5.
