SACCSG HL-2018. Barriers and enablers of a harmonized treatment protocol for childhood and adolescent Hodgkin lymphoma in South Africa.

Introduction: Collaborative studies have contributed to improved survival of pediatric Hodgkin lymphoma in well-resourced settings, but few are documented in resource-constrained countries. The South Africa Children's Cancer Study Group initiated harmonization of management protocols in 2015. This article analyzes barriers and enablers of the process. Methods: Clinician-researchers at 11 state-funded pediatric oncology units completed preparatory questionnaires in June 2018. Parameters included infrastructure, access to therapeutic modalities and clinician numbers. A reassessment of 13 sites (two new pediatric oncology unit) in February 2021 ascertained changes in resources and identified challenges to full participation. Questions investigated the presence and quality of diagnostic radiology, availability of surgeons, cytology/pathology options and hematology laboratory facilities. Results: The response rate was 11/11 to survey 1 and 13/13 to survey 2. The anticipated pre-study barriers to participation of pediatric oncology units included time constraints and understaffing. PET-CT was unavailable to two centers. The majority of pediatric oncology units met the minimum criteria to participate. The interim survey confirmed chemotherapy and radiotherapy availability nearly 100% of the time. One site reported improved access to radiotherapy while another reported improved access to PET-CT. Barriers to participation included excessive times to obtain regulatory approvals, time constraints and lack of dedicated research staff. Enablers include the simple management algorithm and communication tools. Conclusion: This study demonstrates that multicenter collaboration and harmonization of management protocols are achievable in a middle-income setting. Minimal funding is required but full participation to run high-quality studies requires more financial investment. Focused funding and increased prioritization of research may address systemic barriers to full participation.

High incidence of acute kidney injury during chemotherapy for childhood acute myeloid leukemia.

BACKGROUND/OBJECTIVES: Childhood acute myeloid leukemia (AML) is a rare and heterogeneous disease. Pediatric data on the epidemiology of acute kidney injury (AKI) in AML are limited. We report on the incidence of AKI in childhood AML and the risk factors associated with AKI episodes. METHODS: A retrospective cohort of 53 patients (≤18 years), with de novo AML, receiving chemotherapy over a 10-year period. All serum creatinine (SCr) levels during therapy-related hospitalizations were assessed to stage AKI episodes as per Kidney Disease: Improving Global Outcomes criteria. Severe AKI was defined as AKI stages 2 or 3 and urine output criteria were not used. AKI risk factors were assessed independently in both cycle 1 alone and combining all chemotherapy cycles. RESULTS: AKI developed in 34 patients (64%) with multiple AKI episodes in 10 patients (46 total episodes). Twenty-four severe AKI episodes occurred in 23 patients (43.4%) with a mean duration of 26.1 days (SD 7.3). In cycle 1, hyperleukocytosis was not predictive of AKI, but severe sepsis was an independent risk factor of severe AKI (odds ratio [OR]: 13.4; 95% CI 1.9-94.9). With cycles combined, all subjects with AKI had severe sepsis and older age (≥10 years) was associated with severe AKI (OR: 20.8; 95% CI 3.8-112.2). CONCLUSION: There was a high incidence of AKI in our AML cohort with a strong association with older age (≥10 years) and severe sepsis. Larger prospective studies are needed to confirm the high burden of AKI and risk factors in this susceptible population.

Machine Learning to Predict Interim Response in Pediatric Classical Hodgkin Lymphoma Using Affordable Blood Tests.

PURPOSE: Response assessment of classical Hodgkin lymphoma (cHL) with positron emission tomography-computerized tomography (PET-CT) is standard of care in well-resourced settings but unavailable in most African countries. We aimed to investigate correlations between changes in PET-CT findings at interim analysis with changes in blood test results in pediatric patients with cHL in 17 South African centers. METHODS: Changes in ferritin, lactate dehydrogenase (LDH), erythrocyte sedimentation rate (ESR), albumin, total white cell count (TWC), absolute lymphocyte count (ALC), and absolute eosinophil count were compared with PET-CT Deauville scores (DS) after two cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine in 84 pediatric patients with cHL. DS 1-3 denoted rapid early response (RER) while DS 4-5 denoted slow early response (SER). Missing values were imputed using the k-nearest neighbor algorithm. Baseline and follow-up blood test values were combined into a single difference variable. Data were split into training and testing sets for analysis using Python scikit-learn 1.2.2 with logistic regression, random forests, naïve Bayes, and support vector machine classifiers. RESULTS: Random forest analysis achieved the best validated test accuracy of 73% when predicting RER or SER from blood samples. When applied to the full data set, the optimal model had a predictive accuracy of 80% and a receiver operating characteristic AUC of 89%. The most predictive variable was the differences in ALC, contributing 21% to the model. Differences in ferritin, LDH, and TWC contributed 15%-16%. Differences in ESR, hemoglobin, and albumin contributed 11%-12%. CONCLUSION: Changes in low-cost, widely available blood tests may predict chemosensitivity for pediatric cHL without access to PET-CT, identifying patients who may not require radiotherapy. Changes in these nonspecific blood tests should be assessed in combination with clinical findings and available imaging to avoid undertreatment.