Background And Aims: Invasive fungal infections (IFI) in children with newly diagnosed acute lymphoblastic leukemia (ALL) and lymphoblastic lymphoma (LBL) are poorly characterized, especially in lower-middle income countries (LMICs). This study aims to identify the incidence, risk factors and outcomes of IFI in a pediatric cohort with ALL/LBL. Methods: We retrospectively analysed pediatric patients diagnosed with ALL/LBL between January and December 2023 at a tertiary cancer center in India. Patients were risk-stratified and treated per the modified ICiCLe protocol. IFIs were classified as proven, probable and possible according to the revised EORTC/MSG consensus definition. Results: Among 407 patients, 392 (96%) had ALL. The overall incidence of IFI was 24%, with probable/proven infections in 12%. Mold infections predominated (79 cases, 77%), followed by yeast infections (21 cases, 21%). In comparison to patients without IFIs, those with IFIs were more likely to have received dexamethasone (30% vs 20%; p=0.009) and anthracycline (28% vs 14%; p=0.001) during induction. Chemotherapy interruptions occurred in 56% of IFI cases, impacting treatment continuity. The 6-week mortality rate of patients with IFI was 15%, rising to 26% in probable/proven cases. Coexisting bacterial infection was associated with increased mortality (odds ratio: 19.2[95%CI: 3.5-105]; p=0.001). Conclusion: IFIs are common in newly diagnosed ALL/LBL patients in LMICs, particularly during early phases of therapy. These infections are associated with considerable mortality, often compounded by concomitant bacterial sepsis. Given these findings, consideration of antifungal prophylaxis is warranted to mitigate morbidity and mortality due to IFIs.

1 Background Parameningeal Rhabdomyosarcomas (PM-RMS) in children are challenging to treat. While ten-year Event Free Survival (EFS) of 62% have been reported from High-Middle Income Countries (HMICs) for localized disease, data is limited from Low-Middle Income Countries (LMICs). We studied the clinical profile, outcomes, and prognostic factors in PM-RMS. 2 Materials and Methods Children≤15 years with PM-RMS treated on a uniform chemotherapy protocol from January 2013-December 2021 were retrospectively analysed. Local therapy at 10-12weeks of induction was radiotherapy (RT)+/-surgery where possible with early RT for intracranial extension (ICE). 3 Results Seventy-six patients with a median age of 6.7years (range,3.2-15years), male to female ratio of 1.8:1 formed the study cohort. Eleven patients (14.5%) had metastasis (lungs-8, bone-2, bone marrow-1) and ICE seen in 46.1%(n=35). Twenty-five patients (49.0%) had alveolar histology with PAX3/7 positive in 17/59 (28.8%). Median tumor size(t size) at baseline was 5.2cm(range,1.2-12.8cm). Seventy-one patients received RT, 5 also underwent surgery. At a median follow-up of 65months (range,53-76months) 4year EFS, OS of the whole cohort were 47.3%(95%CI:34.8%-58.8%), 51.7%(95%CI:38.0%-64.0%) respectively. Four-year EFS, OS of localized and metastatic cohort were 54.7%(95%CI:41.3%-68.1%), 56.0%(95%CI:42.0%-70.0%) and 9.1%(95%CI:0%-26.5%), 18.2%(95%CI:0%-47.8%) respectively. Metastases (HR-3.38,95%CI:1.57-7.26,p=0.002), t size (HR-1.17,95%CI:1.02-1.34,p=0.026) were prognostic for survival on multivariate analysis. 4 Conclusions Survival of children with localized PM-RMS in our study is relatively fair compared to the reported literature probably due to application of RT in all despite higher proportion of larger tumors, unfavorable sites of primary and intracranial extension. Identification of high-risk subsets and optimizing current treatment strategies, both systemic and local therapy may partly improve outcomes.

1 Background Histopathological response to neoadjuvant-chemotherapy(NACT) measured as tumor necrosis(TN) has been reported to be prognostic of outcomes post HDMTX- based chemotherapy. We studied outcomes based on different cut-offs of TN and delineated clinical-laboratory parameters predictive of TN on a non-HDMTX chemotherapy backbone. 2 Materials and Methods Children ≤15years, with osteosarcoma treated on OGS-2012 protocol and surgery post-NACT from January 2013-December 2020 were retrospectively analysed. TN was reported as percentage necrosis. Kaplan-Meier, log-rank, Pearson’s Chi-square tests were used. 3 Results Analysis was done in 258 patients. Median age-12years(range,3-15years), M:F-1.7:1. Amputation was performed in 20.1%. Median TN was 94%. At a median follow-up of 38months(range,34-45months), 3year Event Free Survival(EFS) and Overall Survival(OS) of the whole cohort were 56.1%(SE,3.3%) and 87.8%(SE,2.4%). For entire cohort, TN-70%(29.3%vs60.7%), 90% (38.7%vs69.0%), 100%(50.8%vs84.1%), were prognostic for EFS(p=0.0001), while TN-90%(80.3%vs92.9%,p=0.006) and 100%(85.5%vs97.7%,p=0.023) were prognostic for OS. For localized disease, TN-70%(35.4%vs 66.4%), 90%(41.6%vs77.0%), 100%(54.8%vs96.2%) were prognostic for EFS(p=0.0001), and OS(p=0.0001). For metastatic disease, TN-70% was prognostic for EFS(16.6%vs50.1%,p=0.0047). Receptor-Operator Curve derived cut-off of 85.5%TN for EFS, 83.5%TN for OS prognosticated whole and localized cohorts the best. For metastatic cohort, 84.5%TN best prognosticated EFS. Among clinical-laboratory parameters, male gender(OR:1.9,p=0.01), amputation (OR:2.1,p=0.014) had a higher risk of <90%TN. 4 Conclusions Tumor necrosis at 90% cut-off in localized disease is prognostic of survival on a non-HDMTX based backbone, though best outcomes are seen with 100%TN, but 70%TN and other cut-offs require further exploration. A lower cut-off of 70%(or other) in metastatic disease could be used for prognostication. Amputation, male gender predicts poor histological necrosis.