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.

1 Background and Objective Coronavirus disease-2019 (COVID-19) or its complications in children with cancer were not increased as compared to normal children in earlier reports. However, continuing intensive treatment during ongoing COVID-19 infection has not been studied systematically. We report a single tertiary center experience on COVID-19 in children with cancer and continuation of cancer-directed therapy in them. 2 Methods Children ≤15years on active cancer treatment detected with COVID-19 until September 15th, 2020 were prospectively followed-up. Patients were managed in accordance to well-laid guidelines. Treatment was continued for children with COVID-19 infection who were clinically stable and on intensive treatment for various childhood cancers as far as practicable. 3 Results One hundred twenty-two children (median age 8years; range 1-15years, male: female 1.7:1) with cancer were diagnosed with COVID-19. All-cause mortality rate was 7.4%(n=9) and COVID-19 related mortality rate was 4.9%(n=6). Of 118 children, 99 (83.9%), 60 (50.8%), 43 (36.4%), 26 (22.0%) and 6 (5.1%) had RT-PCR positivity at 14, 21, 28, 35 and 60 days from diagnosis of COVID-19 respectively. Scheduled risk-directed intravenous chemotherapy was delivered in 70 (90.9%) of 77 children on active systemic treatment with a median delay of 14days (range, 0-48days) and no increased toxicities. 4 Conclusions COVID-19 was not a major deterrent for the continuation of active cancer treatment despite persistent RT-PCR positivity. The long-term assessment of treatment adaptations requires further prospective follow up and real time addressal.

Background: Pediatric B-Lymphoblastic lymphoma(pB-LBL) is a rare entity, and appropriate treatment for pB-LBL is not well defined. While intensive Acute Lymphoblastic leukemia(ALL) type regimens achieve long term event free survival of 90% across western co-operative group trials, published data from Asian studies on long term outcomes in pB-LBL are scarce. We evaluated the outcomes and prognostic factors of pediatric B-LBL patients treated at our center. Methods: We retrospectively analyzed the data of pediatric B-LBL patients treated between January 2010 and December 2017 on a uniform protocol(modified BFM 90). Patients were evaluated for early response post-induction and monitored for toxicity and long term outcomes. Kaplan-Meier method was used to estimate the event free survival(EFS) and overall survival(OS). Cox regression models were performed to identify prognostic factors. Results: Of 21 patients who received treatment on the modified BFM 90 protocol, 17(81%) were alive in remission, 3(14%) had relapse, and 1(4%) had treatment-related mortality(TRM) while in remission. Two of 3 relapsed patients subsequently expired. With a median follow-up of 66 months(range 6–114), 5-year Event free survival(EFS) and overall survival(OS) were 80%(95% CI:71–89%) and 91% (95% CI:85–97%), respectively. While delayed presentation (≥3 months) had inferior EFS(p-0.030), patients with elevated baseline Lactate Dehydrogenase(LDH) had a worse OS(p-0.037). Age, gender, site of origin, stage, and post-induction response had no bearing on outcome. Conclusions: Outcomes of pB-LBL patients treated on modified BFM 90 protocol are excellent. Higher disease burden manifested by elevated baseline LDH and delayed presentation(≥3 months) portend poorer survival.

1 Background Persisting residual mass at treatment completion are known in rhabdomyosarcoma(RMS) who have been treated with definitive radiotherapy to the primary site, but their prognostic significance is uncertain. Tumour response as assessed by anatomic imaging is not prognostic and there are only limited studies based on FDG-PET response. We report the prognostic significance of persistent FDG avidity in residual masses, assessed 3-months post completion of radiotherapy, in paediatric RMS who have undergone definitive RT as primary local therapy. 2 Materials and Methods Children≤15 years with Group 3 or 4 RMS treated on a uniform chemotherapy protocol, who received definitive radiotherapy for local control from June 2013-December 2018, and had FDG-PET CT at 3-months post radiotherapy were retrospectively analysed for outcomes. 3 Results Sixty-three children formed the study cohort, (55 Group3 and 8 Group4) FDG-PET CT scan done 3-months post-radiotherapy showed FDG-avid residual mass in 11 patients(17.5%), morphologic only (FDG negative) residual mass in 24 patients(38.1%) and no residual in 28 patients(44.4%). At a median follow-up of 41months (range,10-83months), 3-year Event Free Survival of patients with FDG-avid residual are 45.5% (95%CI:23.8%-86.8%) and for those with morphologic only or no residual are 71.4% (95%CI:59.6%-85.5%). Presence of FDG-avid residual on PET-CT scan 3-months post definitive RT [HR-2.92(95%CI:1.13-7.57),p=0.028] and regional lymph node involvement [HR-3.14(95%CI:1.26-7.78),p=0.014] affected outcomes, which retained significance on multivariate analysis too. 4 Conclusions Persistent metabolic activity in residual disease at the end of therapy in RMS may portend poorer prognosis, and help identify patients who would benefit from alternative treatment strategy.

Background: The purpose of this single-centre study was to analyse the outcomes of extracranial germ cell tumors (GCTs) in children treated on a multi-modality regimen at a single-centre. Methods: Retrospective study of children (<18 years) with a histopathologically confirmed diagnosis of extracranial GCT over a period of 10 years (January’09-December’18) treated on a uniform institution-based protocol. All completely excised teratomas and stage I gonadal tumors received no further therapy (low risk); Stage IV Ovarian, Stage III-IV extragonadal GCTs received 6 cycles of chemotherapy (high risk) and the remaining received 4 cycles of chemotherapy (intermediate risk). Results: A total of 336 kids were treated of which the analysable cohort comprised of 297with a boy-girl ratio of 1.72:1 and median age of 4 years. Gonadal GCTs(n-180) were commoner than extragonadal GCTs(n-117) with ovary as primary site in 128 children(43%) and sacrococcygeal site being the commonest extragonadal location(n-41;14%). LR, IR and HR disease were noted in 60(20.2%) patients, 125(42%)patients and 112(37.8%)patients respectively. Forty-one patients relapsed and 43 children expired (disease related-33; toxic deaths-9; unknown-1). The 5-year EFS/OS was 79.3%/84.4% respectively with gonadal site, low-risk and non-metastatic disease associated with statistically better EFS (median follow-up:52.1±37.3 months). Conclusion(s): Both cisplatin and carboplatin based regimens had comparable outcomes. The low and intermediate GCTs had an excellent outcome, thus warranting a gradual shift in the approach to these tumors by reducing therapy and decreasing late effects of therapy. In high risk GCTs however, intensifying therapies to improve outcomes must be balanced against the risk of cumulative toxicity.

Survivorship care is a major area of focus in the holistic management of childhood cancer with current knowledge and information almost exclusively from high-income countries. In this review, we summarize the state of scientific knowledge, service delivery, advocacy initiatives and research efforts in this field in India. 21 single centre studies published till date (20 in the last decade) confirm some of the well-documented issues in childhood cancer survivors and also highlight the high prevalence of hepatitis B and hepatitis C infection in our survivors. Heterogeneity in methodology, outcome metrics and quality precludes drawing further conclusions and the ongoing multicenter Indian Pediatric Oncology Group study would address this. Besides the usual model of follow-up clinics in hospital settings, innovative models of service delivery led by not-for-profit organisations are being developed. Advocacy initiatives driven by survivors and support groups are also underway. All of these portend a promising future.

Background: Even though rituximab has emerged as the standard of care for management of high risk paediatric burkitt lymphoma(BL) its safety in children from the low-middle income countries(LMICs) remains to be proven. We herein report our experience of using rituximab in patients with BL treated in our institute. Patients and Methods: All patients diagnosed of BL between January-2015 through December-2017 were treated in a risk stratified manner with either modified MCP-842 or modified LMB protocol. Patients with poor response to MCP 842 were shifted to LMB-salvage regimen. In addition, rituximab was given for selected patients of LMB group B or C. Result: Forty-two(49.4%) of 85 analyzed patients with BL received rituximab [Median dose:1500(Range:375-1875) mg/m2]. The incidence of febrile neutropenia(p=0.02), pneumonia(p=0.005), Intensive care unit admissions(p=0.002) and toxic deaths(p=0.04) were higher amongst BL patients who received rituximab. Pneumonia was fatal in 11 of 16(69%) patients who received rituximab. The mortality was 100% for patients who developed recurrent pneumonia after completion of treatment. On multivariate analysis, rituximab continued to be significantly associated with toxic deaths, HR:11.45(95%CI: 1.87-70.07; p=0.008). The addition of rituximab to intensive chemotherapy resulted in an inferior 1-year event free survival (49.4±8.1% vs 79.3±6.5%;p=0.025) and 1-year overall survival (63.1±8.5% vs 91.8± 4.5%;p=0.007). Also, the addition of rituximab did not improve 1-year relapse free survival (78.3±7.3% vs 83.9±6.0%;p=0.817). Conclusion: The potential immunomodulatory effect of rituximab and increased susceptibility to infections in patients from LMICs being treated under resource-constrained situations has to be carefully considered while choosing this drug in the treatment BL.

Comment on: The COVID-19 Pandemic: A rapid global response for children with cancer from SIOP, COG, SIOP-E, SIOP-PODC, IPSO, PROS, CCI and St. Jude Global.Chetan Dhamne MSc MD1, Tushar Vora MD1, Maya Prasad MD1, Nirmalya Roy Moulik MD PhD1, Badira C Parambil MD DM1, Akanksha Chichra MD1, Girish Chinnaswamy MD1, Shripad Banavali MD1, Gaurav Narula MD11 Department of Medical Oncology, Tata Memorial Hospital, Mumbai, India2. Homi Bhabha National Institute, Anushaktinagar, Mumbai, IndiaCorrespondence to:Gaurav Narula Pediatric Hematolymphoid Disease Management Group, Department of Medical Oncology, Tata Memorial Center, Parel Mumbai, 400012 Email: narulag@tmc.gov.inText word count: 576Brief running title: Letter to Editor (COVID-19) Global responseKeywords: COVID-19, SARS-CoV2, Pediatric Oncology, Children with cancerTables: 1Abbreviations