Matthew A. Kutny

The European LeukemiaNet has periodically issued guidelines for the diagnosis and management of acute myeloid leukemia (AML) in adults. These consensus recommendations, most recently updated in 2022, incorporate recent advances in genomic testing, disease detection methods, target identification, and response assessment. Although similarities exist between AML in children and adults, pediatric AML is frequently characterized by unique cytogenetic and molecular features, which require distinct genetic and immunophenotypic diagnostics, therapeutic approaches, response assessment criteria, and supportive care strategies. To address these specific needs, an international panel of pediatric hematologist-oncologists, biologists, geneticists, and laboratory medicine scientists convened to develop recommendations for the diagnosis and management of AML in children, adolescents, and young adults (hereafter termed pediatric AML) that are discussed in this special report.

Objective: To compare outcomes of obese and nonobese pediatric patients with acute promyelocytic leukemia (APL) from the Cancer and Leukemia Group B trial (CALGB) 9710 and the Children's Oncology Group trial AAML0631.Methods: Data including demographics, adverse events, overall and event‐free survival (EFS) were analyzed.Results: The prevalence of obesity was 34% on C9710 and 35% on AAML0631. There was significantly lower overall and EFS in the obese population on multivariable analysis on AAML0631 but not on CALGB 9710. Eleven patients died during therapy or in follow‐up.Conclusion: The prevalence of obesity is higher in pediatric patients with APL compared to the general population. The decreased EFS and OS in obese patients on AAML0631 suggest that the presence of obesity can influence outcomes using the most current treatment. These findings support the need for further research on the potential role of obesity in pediatric APL leukemogenesis.

The use of all-trans retinoic acid (ATRA) and arsenic trioxide (ATRA/arsenic trioxide) for the treatment of acute promyelocytic leukemia (APL) has been associated with substantial improvements in outcomes, and APL is now the most curable subtype of acute myeloid leukemia. Children in the first North American Intergroup randomized clinical trial (INT0129) who received ATRA during induction therapy and/or maintenance therapy experienced significantly improved disease-free survival compared with those who received conventional chemotherapy only.¹ Intensification of anthracycline and cytarabine chemotherapy in combination with ATRA further improved survival, as observed among children who received ATRA and idarubicin (AIDA) in the AIDA0493 study conducted by the Gruppo Italiano per le Malattie Ematologiche dell'Adulto (GIMEMA)–Italian Pediatric Hematology and Oncology Group (AIEOP).² Patients receiving these intensive treatment regimens, which include high cumulative doses of anthracycline chemotherapy, have a high risk of chronic cardiac toxic effects.^3,4

Langerhans cell histiocytosis (LCH) often has a recurrent and refractory course despite multiagent treatment modalities. Common relapse treatments include intense or prolonged cytotoxic chemotherapy regimens. There are a few prior reports that the nonsteroidal anti-inflammatory drug indomethacin demonstrated activity against bone LCH. Here we report indomethacin as a successful treatment for a case of chronic skin LCH that failed multiple prior chemotherapy regimens. This experience supports the need for trials to investigate indomethacin as a treatment for LCH both in the relapsed or refractory setting as well as potential combination or maintenance therapy in newly diagnosed patients.

Acute promyelocytic leukemia (APL) is characterized by a heightened risk of coagulopathy with significant morbidity and mortality. Here we report our evaluation of presenting white blood cell (WBC) and the International Society on Thrombosis and Haemostasis (ISTH) disseminated intravascular coagulation (DIC) scoring system as markers for early death and nonlethal coagulopathy in pediatric APL. We evaluated 79 pediatric patients treated on a Children’s Oncology Group phase III clinical trial. There were 4 early deaths and 13 nonlethal, clinically significant (grade III to IV) coagulopathy events during induction. Elevated presenting WBC was significantly associated with early death but not with both lethal and nonlethal coagulopathy events. An ISTH DIC score of ≥5 (the original ISTH criteria for overt DIC) was not associated with either early deaths or coagulopathy events. An ISTH DIC score threshold of 6, however, was significantly associated with early death (12% score ≥6 vs. 0% score <6) and with both lethal and nonlethal coagulopathy events (35% score ≥6 vs. 11% score <6). In pediatric APL patients, the presenting WBC is a marker for risk of early death. Although the ISTH score using a cutoff of ≥6 showed improved correlation with adverse coagulation events during induction, the sensitivity was only 70.6% (95% confidence interval, 44.0%-89.7%) and the specificity was 64.5% (95% confidence interval, 51.3%-76.3%). Thus, there is a strong need to identify other biomarkers that can predict APL-associated coagulopathy.

Background: Acute promyelocytic leukemia (APL) is a unique leukemia subtype requiring specialized treatment including all‐trans retinoic acid (ATRA). A prior report demonstrated worse outcome among young children N = 83) with APL treated on North American intergroup study CALGB 9710 at Children's Oncology Group sites. Induction and consolidation included ATRA, cytarabine, and anthracyclines. Patients ≥15 years old were randomized to addition of arsenic trioxide (ATO) consolidation. All patients were randomized to ATRA maintenance with versus without oral chemotherapy.Results: The estimated 5‐year overall survival (OS) rate was 82%, and the event‐free survival (EFS) rate was 54%. Seven patients (8.4%) died during induction due to coagulopathy. Maintenance randomization demonstrated that addition of oral chemotherapy to ATRA significantly reduced relapse rate, but difference in EFS did not reach statistical significance (P = 0.12; 5‐year rates [95% CI]: 41% [17%–64%] ATRA only vs 72% [56%–88%] ATRA plus chemotherapy). There was no difference (P = 0.93) in EFS for age P = 0.02).Conclusion: Our data demonstrate that intensified ATRA, cytarabine, and anthracycline chemotherapy is effective for pediatric APL including very young patients, but early deaths and relapses remain barriers to cure. Further improvements are likely with incorporation of ATO into pediatric APL regimens.

Introduction: In patients who are immunocompromised, fever may indicate a life-threatening infection. Prompt time to antibiotic administration in febrile patients at risk for neutropenia has been identified by national and international panels as a key benchmark of quality care in emergent situations. A quality improvement initiative to improve health care provided in a pediatric emergency department (ED) is described. Methods: A clinical pathway was previously initiated in a pediatric ED with a goal of improving time to antibiotics for febrile neutropenia patients. An agreed upon pathway and order set being initiated. Improvements were seen but not to the desired level. This project involved an improvement cycle that focused on nonvalue added time in the workflow. Results: Percent of patients receiving antibiotics within the goal time of 1 hour increased from 40% to 80% with the intervention. Process measures including arrival to ED bed time, ED bed to antibiotic order time and antibiotic order time to delivery time were followed. Conclusion: Clinical guidelines, order sets and detailed understanding of the actual workflow at the point of care delivery can be instrumental in achieving the goals of reducing time to antibiotics.