Although survival in pediatric acute myeloid leukemia (AML) has increased considerably over the past decades, refractory disease and relapse rates remain high. Refractory and relapsed disease are difficult to treat, with overall survival rates less than 40–50%. Preventing relapse should, therefore, be one of the highest priorities. Current conventional chemotherapy regimens are hard to intensify due to associated toxic complications, hence more effective therapies that do not increase toxicity are needed. A promising targeted agent is the CD33-directed antibody–drug conjugate gemtuzumab ozogamicin (GO). Because CD33 is highly expressed on leukemic cells in the majority of AML patients, GO can be useful for a broad range of patients. Better relapse-free survival (RFS) after therapy including GO has been reported in several pediatric clinical trials; however, ambiguity about the clinical value of GO in newly diagnosed children remains. Treatment with GO in de novo AML patients aged ≥1 month, in combination with standard chemotherapy is approved in the United States, whereas in Europe, GO is only approved for newly diagnosed patients aged ≥15 years. In this review, we aimed to clarify the clinical value of GO for treatment of newly diagnosed pediatric AML patients. Based on current literature, GO seems to have additional value, in terms of RFS, and acceptable toxicity when used in addition to chemotherapy during initial treatment. Moreover, in KMT2A -rearranged patients, the clinical value of GO was even more evident. Also, we addressed predictors of response, being CD33 expression and SNPs, PgP-1 and Annexin A5. The near finalized intent-to-file clinical trial in the MyeChild consortium investigates whether fractionated dosing has additional value for pediatric AML, which may pave the way for a broader application of GO in pediatric AML.

PurposeThe Pediatric Oncology in Developing Countries (PODC) committee of the International Society of Pediatric Oncology (SIOP) published a pediatric acute myeloid leukemia (AML)‐specific adapted treatment guideline for low‐ and middle‐income countries. We evaluated the outcomes of children with AML at a large Kenyan academic hospital before (period 1) and after (period 2) implementing this guideline.Patients and MethodsRecords of children (≤17 years) newly diagnosed with AML between 2010 and 2021 were retrospectively studied. In period 1, induction therapy comprised two courses with doxorubicin and cytarabine, and consolidation comprised two courses with etoposide and cytarabine. In period 2, a prephase with intravenous low‐dose etoposide was administered prior to induction therapy, induction course I was intensified, and consolidation was adapted to two high‐dose cytarabine courses. Probabilities of event‐free survival (pEFS) and overall survival (pOS) were estimated using the Kaplan–Meier method.ResultsOne‐hundred twenty‐two children with AML were included – 83 in period 1 and 39 in period 2. Overall, 95 patients received chemotherapy. The abandonment rate was 19% (16/83) in period 1 and 3% (1/39) in period 2. The early death, treatment‐related mortality, complete remission, and relapse rates in periods 1 and 2 were 46% (29/63) versus 44% (14/32), 36% (12/33) versus 47% (8/17), 33% (21/63) versus 38% (12/32), and 57% (12/21) versus 17% (2/12), respectively. The 2‐year pEFS and pOS in periods 1 and 2 were 5% versus 15% (p = .53), and 8% versus 16% (p = .93), respectively.ConclusionThe implementation of the SIOP PODC guideline did not result in improved outcomes of Kenyan children with AML. Survival of these children remains dismal, mainly attributable to early mortality.