Quantifying the difference in risk of adverse events by induction treatment regimen in pediatric acute lymphoblastic leukemia.

The differences in overall morbidity by induction treatment regimen for pediatric acute lymphoblastic leukemia (ALL) are unknown. We examined a cohort of children with ALL who received induction chemotherapy between January 2010 and May 2018. We evaluated 20 clinically relevant adverse events (AEs) and readmission and ICU admission rates. Outcomes were compared between standard 3- and 4-drug treatment regimens in multivariate analyses using Cox proportional hazard ratios. Among 486 eligible patients, the risks of sepsis (HR = 2.16, 95% CI = 1.11-4.19), hypoxia (HR = 2.08, 95% CI = 1.03-4.18), hyperbilirubinemia (HR = 2.48, 95% CI = 1.07-5.74), hyperglycemia (HR = 2.65, 95% CI = 1.29-5.42), thromboembolic event (HR = 4.50, 95% CI = 1.30-15.6), and hyponatremia (HR = 7.88, 95% CI = 1.26-49.4) were significantly higher during 4-drug induction. Despite no differences in readmission or ICU admission rates, 4-drug induction patients had greater total inpatient days (12 vs. 4 days; p<.0001). In conclusion, pediatric patients receiving 4-drug induction for ALL experience higher morbidity. These results inform care practices and patient guidance during induction therapy.

A strategy to reduce cumulative anthracycline exposure in low-risk pediatric acute myeloid leukemia while maintaining favorable outcomes.

BACKGROUND: Advances in risk stratification have improved the 3-year disease-free survival (DFS) and overall survival (OS) of low-risk pediatric acute myeloid leukemia (LR-AML) to approximately 70 % and 85 % respectively. LR-AML is defined by favorable cytogenetic/molecular features and/or optimal early response to therapy. However, cumulative anthracycline exposure in contemporary Children's Oncology Group (COG) regimens approach a doxorubicin equivalent exposure of 540 mg/m2; with rates of non-infection related left ventricular systolic dysfunction (LVSD) approaching 15 %. This is a major cause of toxicity in these patients and precludes the further use of anthracyclines in the relapsed setting; therefore, strategies that reduce cardiotoxicity while maintaining excellent outcomes are needed. PATIENTS AND METHODS: Twenty-seven pediatric patients with LR-AML were treated with an anthracycline-reduced approach (Aflac-AML regimen) between 2011 and 2016. Patients received four courses of therapy including three high-dose cytarabine containing courses and a cumulative doxorubicin equivalent exposure of 390 mg/m2, a 28 % reduction in anthracycline dosing compared to current COG regimens. RESULTS: The 3-year DFS and OS was 70.0 % and 85.5 % respectively, from end of Induction I (first chemotherapy cycle) with a median follow-up of 3.2 years. These survival outcomes are comparable to current LR-AML regimens. Only two patients developed non-infection related LVSD during therapy and more importantly, none developed LVSD after completion of therapy. CONCLUSION: These findings suggest that LR-AML outcomes can be maintained using a reduced anthracycline chemotherapy regimen, resulting in lower cardiac toxicity. This new chemotherapy backbone is now being tested prospectively (NCT04326439) to further validate its use in pediatric LR-AML.