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.

B-cell acute lymphoblastic leukemia (B-ALL) is a heterogeneous disease wherein cytogenetics comprises an independent prognostic factor. Cytogenetic subgroups like B-ALL with t(9;22), MLL rearrangement, hypodiploidy, and Ph-like ALL are stratified as high-risk and are treated on the high-risk regimen. However, a subset that does not fall into a specific cytogenetic risk groups, is classified as cytogenetics NOS (Not Otherwise Specified) and might receive suboptimal chemotherapy. Identifying genetic abnormalities that are susceptible to targeted therapy can help improve outcomes. Therefore, with the intent to report cytogenetic data potentially useful for targeted therapy, we report a novel JAK2 amplification in a cytogenetically complex pediatric B-ALL case with early relapse.

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.

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.

Background: JMML is a pediatric haematopoietic stem cell malignancy characterised by uncontrolled proliferation of myelomonocytic and progenitor compartments and a poor outcome. We comprehensively evaluated the genomic profile of JMML that presented to our hospital for diagnosis and treatment. Procedure: We developed a 51-gene (151.5kB) low-cost targeted myeloid panel based on single-molecule molecular inversion probes. A total of 50 children with clinical and pathological features of JMML were sequenced at high coverage on an Illumina MiSeq. The presenting clinical, laboratory and follow-up data were procured from the electronic medical record system of the institution. Results: The median age of our cohort was 2 years, with a male preponderance. Among the 50 patients, 43 (86%)harboured mutations in one of the RAS/MAPK-pathway genes, most frequently in PTPN11 (14, 28%), and NRAS (14, 28%), followed by NF1(11. 22%). Interestingly, 20% (10) of children had more than one mutation, with 5 cases harbouring two RAS-pathway mutations. Monosomy 7 was detected in 32% (16) patients, and five of these did not harbour any RAS-pathway mutations. The follow-up data revealed that 37 (74%) of these children had succumbed to the disease. Children with monosomy 7 showed shorter overall survival, compared to their wildtype counterparts (p=0.02). Conclusion: Our study highlights that comprehensive genomic profiling identifies at least one mutation in almost 90% of JMML patients. Performing genomic analysis early in evaluation of JMML might help in triaging patients for allogenic stem cell transplant in resource-constrained settings.

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