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Background: Acute myeloid leukemia with normal cytogenetics (CN-AML) is the largest group of AML patients with very heterogenous patient outcomes. The revised World Health Organization classification of the hematolymphoid tumours, 2022, has incorporated AML with Nucleophosphmin1 (NPM1) and CCAAT/enhancer binding protein-alpha (CEBPA) mutations as distinct entities. Despite the existing evidence of the prognostic relevance of FMS-like tyrosine kinase-3 internal tandem duplication (FLT3-ITD) in AML, it has not been included in the revised classification. Method: In this prospective study, we determined the prevalence of NPM1, CEBPA, and FLT3 gene mutations in 151 de novo CN-AML adult patients (age ≥18 years) in a tertiary care hospital in north India. Additionally, the prognostic relevance of these mutations was also evaluated. Results: NPM1, FLT3-ITD, and CEBPA mutations were found in 33.11%, 23.84%, and 15.77% of CN-AML patients, respectively. CEBPA mutations were found at 3 domains: transactivation domain 1 (TAD1) in 10 (6.62%), transactivation domain 2 (TAD2) in 5 (3.31%), and basic leucine zipper domain (bZIP) in 11 (7.82%) patients. Patients with NPM1 mutation had better clinical remission rate (CR) (P=0.003), event-free survival (P=0.0014), and overall survival (OS) (P=0.0017). However, FLT3-ITD and CEBPA mutations did not show any association with CR (P=0.404 and 0.92, respectively). Biallelic CEBPA mutations were found in 12 (7.95%) patients and were associated with better OS (P=0.043). Conclusions: These findings indicate that NPM1 and CEBPA mutations can be precisely used for risk stratification in CN-AML patients.

TPS12149 Background: Chemotherapy-induced nausea and vomiting (CINV) is a common adverse effect affecting quality of life of patients of cancer undergoing chemotherapy. Carboplatin alone or in combination with various other chemotherapy drugs is one of the most commonly used drug in solid malignancies. It is categorised as a highly emetogenic drug in doses above AUC≥4 and multiple past studies revealed high CINV incidence. Current international antiemetic guidelines suggest NK1 receptor antagonist based triplet drugs as an effective regimen of CINV control in these patients. However, the nausea control rates are largely inadequate. Olanzapine, an atypical antipsychotic drug, is another drug that has shown significant activity in CINV control and is an integral part of current chemotherapy induced emesis and nausea prevention. However, robust comparative studies of olanzapine based triplets with NK1 based combination have been lacking. Hence we planned this study to compare efficacy of olanzapine containing triplet with NK1 receptor antagonist (fosaprepitant) based triplet drug combination in a phase 3 randomised study. Methods: This study is an investigator initiated phase 3 prospective randomised double blind placebo controlled trial comparing efficacy of olanzapine, 5HT3 receptor antagonist(ondansetron) and dexamethasone (experimental arm) against fosaprepitant, 5HT3 receptor antagonist(ondansetron) and dexamethasone (standard arm) for prevention of CINV among chemo-naïve patients (aged ≥18 years) receiving carboplatin (AUC ≥4) based chemotherapy regimen. Primary objective is to compare the number of patients with no nausea during overall periods (0-120 hours post-chemotherapy). Secondary objectives are to compare complete response (no emetic episodes and no use of rescue medication) in the acute(0-24 hr), delayed(25-120 hr),overall periods(0-120 hr) and to assess the frequency of rescue medication use. The other secondary objective includes assessment of adverse events in both the arms. Statistical Design: Planned accrual is total 214 patients including 10% drop out rate. It is a superiority design with an absolute improvement of 20% in the proportion of patients with no nausea from a baseline prevalence of 40% in the standard arm and two sided alpha of 5% as well as power of 80%. Conduct to date :Study activation : March 2021. Enrolment : 138 subjects. Clinical trial information: CTRI/2021/03/032165.

Emerging evidence suggests existence of three prognostically relevant molecular entities among immature T-ALL-early thymic precursor ALL (ETP-ALL), T-ALL with the absence of biallelic deletion of TCRγ chains (ABD) and MEF2C (Myocyte Enhancer Factor 2C) high T-ALL. However, the usefulness of ETP-ALL immunophenotype and assessment of ABD for this purpose has been questioned and, MEF2C has not been studied in much detail. In this prospective analysis of 143 T-ALL patients, we evaluated the mutual association of these three entities and also determined how immunophenotypically-defined poor prognosis immature T-ALL relates to these entities. We found that all three of them, especially ABD, nearly completely characterized the immature group. High MEF2C expression reflected ETP-ALL somewhat poorly and a few ABD and MEF2C-high patients had non-immature immunophenotype-findings, that though in accord with published literature, call for exploration per T-cell receptor (TCR) classification scheme. ETP-ALL and MEF2C high but not ABD had a higher frequency of minimal residual disease positivity and poor event-free survival. MEF2C high, not ETP-ALL immunophenotype or ABD, had poorer overall survival. The value of ETP-ALL immunophenotype and MEF2C status, as indicators of poor treatment response, needs further evaluation for possible incorporation in standard T-ALL management practice.

Deepam Pushpam,1,* Vikas Garg,1,* Sandip Ganguly,2 Bivas Biswas2 1Department of Medical Oncology, AIIMS, New Delhi, India; 2Department of Medical Oncology, Tata Medical Center, Kolkata, India*These authors contributed equally to this workCorrespondence: Bivas BiswasDepartment of Medical Oncology, Tata Medical Center, 14 MAR [EW] New Town, Rajarhat, Kolkata 700160, IndiaTel +91033 6605 7628Email bivasbiswas@gmail.comAbstract: Paediatric sarcomas are a heterogeneous group of disorders constituting bone sarcoma and various soft tissue sarcomas. Almost one-third of these presents with metastasis at baseline and another one-third recur after initial curative treatment. There is a huge unmet need in this cohort in terms of curative options and/or prolongation of survival. In this review, we have discussed the current treatment options, challenges and future strategies of managing relapsed/refractory paediatric sarcomas. Upfront risk-adapted treatment with multidisciplinary management remains the main strategy to prevent future recurrence or relapse of the disease. In the case of limited local and/or systemic relapse or late relapse, initial multimodality management can be administered. In treatment-refractory cases or where cure is not feasible, the treatment options are limited to novel therapeutics, immunotherapeutic approach, targeted therapies, and metronomic therapies. A better understanding of disease biology, mechanism of treatment refractoriness, identifications of driver mutation, the discovery of novel targeted therapies, cellular vaccine and adapted therapies should be explored in relapsed/refractory cases. Close national and international collaboration for translation research is needed to fulfil the unmet need.Keywords: paediatric sarcoma, immunotherapy, targeted therapy, relapsed sarcoma, osteosarcoma, disease biology

e24081 Background: Assessment of physical and psychological symptoms using patient-reported outcome (PRO) scales is an often overlooked aspect in oncological practice in resource constrained settings. We assessed the pattern of symptoms at diagnosis in solid organ cancers using an innovative smart device based delivery of the Edmonton Symptom Assessment Scale (ESAS). Methods: We assessed PROs using ESAS at diagnosis in adult patients diagnosed with solid organ cancers at a large tertiary care centre in New Delhi, India from September 2021 to January 2022. The ESAS was delivered to patient's smart phone as a text message that provided a unique link to complete the questionnaire in Hindi or English, as preferred by the patient. Symptom severity was categorized into physical, psychological, and total symptom domains and the scores were further classified as none to mild (0-3) or moderate to severe (4-10). Univariate and Multivariate logistic regression analyses were performed to determine predictive factors. Results: Text message with ESAS completion link was sent to 653 consecutive patients, of whom 509 (77.9%) completed the questionnaire during the study period. The median age was 52 years and 53.2 % were males. The primary cancer site was lung, breast, gastrointestinal, and others in 27.7%, 28.1%, 14.4%, and 29.8%, respectively. Pain (59.1%) and tiredness (57.8%) constituted the maximum physical symptom scores in moderate and severe category. Patients with lung cancer had most physical symptoms categorised in moderate and severe compared with other cancers (P = 0.03), while psychological symptoms were more likely to be moderate to severe females (P = 0.01). In the multivariable logistic regression analysis after adjusting for measured confounders, primary cancer site (lung vs others) and sex (female vs male) were significant predictors for moderate and severe physical and psychological symptoms, respectively. Conclusions: A simple mobile-based ESAS delivery system can help in collecting PRO data to assess symptom burden in patients diagnosed with cancer. The symptom burden assessment can aid in providing personalised symptom-directed measures to improve the quality of life of patients with cancer.