Bishwaranjan Jana

Abstracts Pediatric Hematology Oncology Journal 8 (2023) S13eS99 AUTOLOGOUS STEM CELL TRANSPLANT IN PEDIATRIC ONCOLOGY: INSIGHTS FROM A SOUTH INDIAN TERTIARY CARE HOSPITAL SYSTEMATIC CLINICAL AND PHARMACOLOGICAL MONITORING OF A PEG-ASPARAGINASE BIOGENERIC (HAMSYL) IN PAEDIATRIC PATIENTS WITH NEWLY-DIAGNOSED ACUTE LYMPHOBLASTIC LEUKAEMIA Amrit Kaur, Vasundhara Kailasnath, A.M. Gayathri, Siddhanth Shetty, L. Appaji, B.S. ArunaKumari. Kidwai Memorial Institute of Oncology, Bangalore, India Duhita Sengupta, Bishwaranjan Jana, Bony Dasgupta, Srijani Goswami, Subhajit Kundu, Samik Samaddar, Arko Bhowal, Annwesha Roy, Debjani Ghosh, Niharendu Ghara, Jasmeet Sidhu, Neerajana Datta. Tata Medical Center, Kolkata, India; Tata Translational Cancer Research Centre, Tata Medical Center, Kolkata, India Background: Autologous stem cell transplant (ASCT) is a part of therapeutic strategy for various pediatric malignancies. Our aim is to assess the clinicodemographic profiles and outcomes of pediatric cancer patients who underwent ASCT at our institution. Methods: This was a retrospective study including children under 15 years of age who underwent ASCT from March 2022 to August 2023. Data was extracted from hospital records and patient follow up continued until August 2023. Results: A total of 15 patients were included, with a median age of 9 years (range e 2 to 14 years), and 67% were male. Hodgkin lymphoma (HL) was the most prevalent primary diagnosis (53.3%), followed by neuroblastoma (40%). All HL cases presented with advanced-stage at diagnosis, with 75% classified as refractory disease. The primary second-line treatment employed was Ifosfamide carboplatin and etoposide (ICE) (62.5%). All patients exhibited complete metabolic responses (CMR) on pre-transplantation positron emission tomography and computed tomography scans (PET CT). In the case of neuroblastoma, initial therapy adhered to the POG 9341 protocol, with 50% of patients demonstrating NMYC positivity. Notably, 50% lacked CMR pre-ASCT. Conditioning regimens included BCNU, etoposide, cytosine arabinoside, and melphalan (BEAM) in 66.6% of cases and Busulfan and melphalan (Bu-Mel) in 33.3%. Stem cell storage averaged 81 days. Febrile neutropenia was a universal occurrence, with 86.6% reporting grade 3 to 4 diarrhea, and 26.6% testing positive for entamoeba histolytica in stool cultures. Median time to neutrophil and platelet engraftment were 12 days and 15 days, respectively. At a median follow-up duration of 288 days, 86.6% of patients remained alive, while 13.3% succumbed to progressive disease. None of the fatalities were attributed to transplant-related complications. Conclusions: ASCT is the standard of care for relapsed/refractory HL and plays a pivotal role in the consolidation therapy of high-risk neuroblastoma within the pediatric oncology context. Background: Asparaginase is a critical anti-leukaemic drug. Polyethyleneglycol (PEG) formulations have extended activity and lower immunogenicity. Limited access to innovator asparaginases has spurred proliferation of biogeneric substitutes, the majority inadequately characterised. Studies with Hamsyl, an indigenous PEG-asparaginase biogeneric (Gennova Biopharmaceuticals, India), show satisfactory first-dose pharmacokinetics and adequate drug activity. We expand on these observations, reporting findings from a systematic institutional Hamsyl monitoring programme. Methods: Between Aug’20-March’23, patients 1-18 years with newlydiagnosed acute lymphoblastic leukaemia received 2-7 Hamsyl doses (intramuscular, 1000 IU/m2) as part of risk-stratified treatment, and monitored for asparaginase-associated toxicities. Plasma samples were assayed serially for asparaginase activity (aspartate-b-hydroxamate/ indooxine assay) and anti-drug-antibody. Trough asparaginase activity <100 IU/L was deemed sub-therapeutic. Patients with silent inactivation had persistent below-quantification drug activity without clinical hypersensitivity. Treatment implementation involved Hamsyl dose-sharing (two 3750IU vials/5 patients), coupled with drug donation. Results: The study enrolled 173 patients (median, 5$1 years). Asparaginase activity was monitored serially through treatment in 79% patients. Satisfactory trough activity (100 IU/L) was observed in 88% samples (470/ 535), including 93% in induction (209/225) and 84% (261/310) post-induction. Median activity was 567 IU/L (interquartile, 341-770), significantly higher post- induction (629 versus 467 IU/L, p<0$001). Eight patients (4$6%) developed clinical hypersensitivity, all with undetectable asparaginase activity. Silent inactivation was observed in 9$4% patients (15/160), including 3 with persistent undetectable drug activity through treatment. Nine (5$2%) developed asparaginase-associated pancreatitis (8, mild; 1, moderately-severe; no sequelae); patients were significantly older (median, 11$6 years; p¼0$008). With vial donation/dose-sharing, patients paid only for 25% (156/624) of administered doses. Conclusions: Findings confirm Hamsyl as a suitable asparaginase biogeneric. Toxicity rates, although acceptable, indicate continuing requirement for better asparaginases. Our experience highlights importance of pharma partnerships in enabling access and evaluation of essential anticancer drugs. A similar partnership is envisaged for expanded access to an affordably- priced lower-strength single-dose Hamsyl formulation at ALL study centres. CYCLOPHOSPHAMIDE-TOPOTECAN: A POTENTIAL SALVAGE REGIMEN FOR RELAPSED PEDIATRIC SOLID CANCERS? T. Pragadeesh, Gargi Das, Prasanth Srinivasan, Balaji Thiruvengadam Kothandan, Venkatraman Radhakrishnan. Cancer Institute (WIA), Chennai Background: Relapsed pediatric solid cancers have very limited options for salvage chemotherapy and are associated with poor outcomes. Table 1 Summary of plasma Asparaginase activity measurements recorded 12e16 days post PEG-ASNase administration * p ¼ 1.5843E-7 S48 # p ¼ .002.