Large Language Models (LLMs) extracts structured data from unstructured Ga-68 Prostate Specific Membrane Antigen Positron Emission Tomography/Computed Tomography (PSMA PET/CT) reports by interpreting context and semantics, enabling reliable conversion of free-text into structured, queryable data. We evaluated whether locally deployed Llama 3.2:3b and Gemma 2:2b models could accurately perform zero-shot extraction of key diagnostic features. We retrospectively selected 50 de-identified Ga-68 PSMA PET/CT reports of histologically confirmed prostate cancer (01 January 2020–30 June 2024), ensuring rigorous expert annotation and inter-reader agreement. Reports were batch-processed using standardized zero-shot and few-shot prompts applied to locally deployed Llama 3.2:3b and Gemma 2:2b models, with model outputs benchmarked against an adjudicated dual-expert ground truth reference derived from independent annotations and consensus resolution of discrepancies using standard performance metrics. Both Llama 3.2:3b and Gemma 2:2b achieved rapid, reliable extraction of key diagnostic features from Ga-68 PSMA PET/CT reports, with excellent inter-reader agreement (average κ = 0.882). Llama 3.2:3b offered superior sensitivity (83.7

e17073 Background: Metastatic prostate cancer remains difficult to manage due to treatment resistance and cumulative toxicity of systemic therapies. Beta-sitosterol, a dietary phytosterol, has demonstrated anticancer activity in preclinical prostate cancer models and symptomatic benefit in benign prostatic hyperplasia, but clinical evidence in prostate cancer is lacking. Additionally, circulating ceramides are emerging as potential biomarkers of tumor burden and disease progression. This pilot trial was designed to evaluate the feasibility, safety, and preliminary clinical effects of beta-sitosterol in metastatic prostate cancer. The aim was to assess the effect of add-on beta-sitosterol supplementation on prostate-specific antigen (PSA) levels, urinary symptoms, safety, and tolerability in patients with metastatic prostate cancer, and to explore the relationship between baseline plasma ceramide levels and PSA. Methods: This was a randomized, double-blind, placebo-controlled, parallel-group pilot trial conducted. Forty-one men with biopsy-proven metastatic prostate cancer were randomized to receive either beta-sitosterol 320 mg once daily (n≈20) or placebo (n≈21) for three months, in addition to standard therapy. The primary outcome was the least-squares mean difference in log₁₀ PSA at three months. Secondary outcomes included changes in International Prostate Symptom Score (IPSS) and safety. Plasma ceramide levels were measured at baseline using ELISA. Results: At three months, there was no statistically significant difference in log₁₀ PSA levels between the beta-sitosterol and placebo groups (p > 0.05). However, patients receiving beta-sitosterol showed a greater reduction in IPSS scores over follow-up, with a higher proportion shifting from moderate-to-severe symptoms to milder categories compared to placebo (p < 0.05). Beta-sitosterol was well tolerated, with no serious adverse events and only mild gastrointestinal complaints reported. Baseline plasma ceramide levels showed a significant positive correlation with PSA (Pearson correlation, p < 0.05), suggesting an association with tumor burden. Conclusions: Add-on beta-sitosterol was safe and improved urinary symptoms but did not significantly reduce PSA levels. Larger trials are required to confirm efficacy and validate ceramide as a prognostic biomarker. Clinical trial information: CTRI/2024/02/063329.

BACKGROUND:Alterations in genes involved in homologous recombination repair (HRR) occur in approximately 20%-25% of patients with metastatic prostate cancer and are associated with aggressive biology, poor outcomes, and potential sensitivity to poly (ADP-ribose) polymerase inhibitors (PARPi). However, frequency and variations in somatic HRR mutations in the Indian population are unknown. METHODS:We analyzed somatic HRR alterations in patients at the All India Institute of Medical Sciences, New Delhi, between 2022 and November 2024. Targeted next-generation sequencing of 15 HRR genes was performed on tumor tissue samples. Demographic and clinicopathological variables were retrieved from medical records, and their associations were assessed. RESULTS:Of 247 patients tested, 167 were evaluable (32.3% tissue failure due to poor DNA yield). Sixty-eight pathogenic HRR alterations were detected across 51 patients (30.5%). ATM was the most frequently altered gene (13.2%), followed by BRCA1 (5.3%), BRCA2 (4.2%), and CDK12 (4.2%). Variants of unknown significance (VUS) were detected in 12% (20) of patients. Patients with HRR alterations had higher baseline PSA values compared with the non-HRR cohort (median 150 vs 100 ng/mL, P = .012). No significant associations were observed with age, Gleason score, disease volume or risk category, or visceral metastases. CONCLUSIONS:This study provides the first comprehensive dataset on the spectrum of somatic HRR mutations in Indian patients with prostate cancer. The prevalence (30.5%) was somewhat higher than the global studies, ATM was the most frequently mutated gene, followed by BRCA1, in contrast to Western and Asian cohorts, where BRCA2 predominates. These findings suggest potential population-specific variations and underscore the need for broader HRR testing to better delineate the genomic landscape of prostate cancer in Indian patients.

BACKGROUND:Acute graft-versus-host disease (aGvHD) is a major immune complication of allogeneic hematopoietic stem cell transplantation (Allo-HSCT), driven by complex immune-cytokine interactions. This study employed machine learning (ML) algorithms to develop early predictive models for aGvHD using immune and cytokine profiles of Allo-HSCT recipients at the time of engraftment. MATERIALS AND METHODS:Seventy patients with hematological disorders undergoing their first Allo-HSCT were recruited prospectively. Peripheral blood immune subsets and cytokines were analyzed using flow cytometry and ELISA, respectively. ML models, including support vector classifier (SVC), decision tree, and random forest, were trained on 48 features: 34 immune subsets and 14 cytokines. RESULTS:Patients who developed aGvHD exhibited a reduced CD4+/CD8+ ratio, lower Tregs, elevated Th1, Th17, cytotoxic natural killer (NK) cells, dendritic cells (DCs), B cell, and increased proinflammatory cytokines (IFN-γ, IL-1β, IP-10, TNF-α, IL-17α, IL-12p70, MIP-1α, MIP-1β, and RANTES). ML models demonstrated excellent predictive performance, with cytokine profiles alone or combined with immune data achieving perfect accuracy (1.00), followed by T-cell (0.96), NK cell (0.93), DC (0.90), and B cell (0.86) models. CONCLUSION:Cytokine profiles emerged as superior predictors over immune subsets, supporting their integration into ML-based aGvHD risk prediction. These findings provide a foundation for developing biomarker-guided strategies for early aGvHD detection and management.

Diffuse large B-cell lymphoma (DLBCL) is molecularly heterogeneous, yet standard cell-of-origin (COO) classification fails to capture actionable biology. Systematic genetic profiling remains unmapped in South Asian populations, who exhibit a decade-younger age of onset. We performed targeted next-generation sequencing on pre-treatment diagnostic biopsies from 186 Indian DLBCL patients to evaluate LymphGen molecular subtyping against COO classification. LymphGen re-stratification showed that every COO category contained multiple genetic subtypes with distinct driver genes, co-mutation patterns, and mutation types. This COO–genotype mismatch persisted even when we modelled perfect COO assignment, indicating it is structural, not a artefact of imperfect immunohistochemistry. The MCD subtype (18.8%) was missense-predominant (71.3% missense), characterised by recurrent MYD88 and CD79B mutations consistent with proximal NF-kB/BCR activation, whereas EZB (22.6%) and BN2 (18.3%) were truncation-predominant, consistent with tumour-suppressor loss. This cohort demonstrated enrichment of N1 (9.1% vs ∼3% Western) and A53 (15.6% vs ∼12% Western) subtypes. A53 carried the highest LOH/biallelic signature (21.3% of mutations at VAF >50%), consistent with TP53 biallelic inactivation and known poor prognosis under standard immunochemotherapy. Independent of COO, VAF-based clonal ordering identified TP53 and MYD88 as early founding events versus late BCL2/SGK1 acquisition. Furthermore, genetic subtyping reassigned risk biology in 17% of non-GCB and 23% of GCB cases, resolving all 32 COO-unclassified cases. Overall, 72% of patients carried at least one actionable lesion. These data provide an early Indian molecular reference and support integrating targeted molecular classifiers as adjuncts to comprehensive LymphGen and FISH in frontline workflows.

IntroductionAutologous hematopoietic stem-cell transplant(ASCT) following high-dose chemotherapy is an established treatment for selected pediatric solid tumors. However, data from low- and middle-income countries(LMICs) remain scarce, where outcomes may be influenced by limited supportive care infrastructure and higher infection risks. Most available reports focus primarily on neuroblastoma, with little evidence for other solid tumors.MethodsThe study included children, adolescents, and young adults (CAYA,0–25 years) with solid tumors treated at a tertiary-care center in India, aiming to assess survival outcomes, engraftment kinetics, and toxicities. Data were collected from patient files and electronic databases for those who underwent ASCT between January 2008 and June 2025.ResultsOut of 92 patients, median age was 6y (IQR,4-16) with 69.6% males. Diagnoses included: high-risk neuroblastoma(HRNB,52.2%), relapsed/refractory Ewing sarcoma(EWS,22.8%), relapsed/refractory germ-cell tumors(GCT,15.2%), retinoblastoma(RB,5.4%), and soft-tissue sarcoma (STS,4.4%). Forty-three (46.8%) underwent ASCT in relapse/refractory setting, while 49(53.2%) had upfront ASCT. Median CD34+cell dose was 5.7(IQR,3.5-6.9) million/kg, with a median cryopreservation duration of 16(IQR,8-49) days. Median time to neutrophil-engraftment was 11(IQR,9-12) days. The 3-year OS of the entire cohort was 50.6% (95%CI: 36.8-62.9), and EFS was 35.9% (95%CI: 23.6-48.3). Three-year OS for HRNB, relapsed/refractory-EWS, relapsed/refractory-GCT, STS and RB were 48.5%(95%CI: 29.2-65.3), 43.8% (95%CI: 17.8-67.4), 56.3%(95%CI: 20.9-80.9), 66.7% (95%CI: 5.4-94.5), and 50.0%(95%CI: 6.0-91.0), respectively. For HRNB and EWS, BuMel-140 had better OS than CEM-200 [HR = 0.15,95%CI:0.04-0.7,p=0.005].ConclusionASCT yields acceptable outcomes for selected high-risk or relapsed/refractory pediatric solid tumors in LMICs, with outcomes in GCT comparable to global standards, based on experience from a high-volume transplant center.

204 Background: Approximately one-fourth of patients with metastatic castration resistant prostate cancer (mCRPC) harbor mutations in homologous recombination repair (HRR) pathway genes. However, access to PARP inhibitors remains limited in LMICs. Carboplatin has been inadequately researched in such settings. Methods: We conducted a phase II single arm clinical trial at a tertiary care cancer centre in Northern India. Eligible patients harboring a mutation in the HRR pathway genes and previously treated with at least one androgen pathway receptor inhibitor, who did not have access to PARP inhibitors were treated with single agent carboplatin (dose: area under curve 5) every 3 weeks. The primary endpoint was PSA50 response, defined as a confirmed decline in serum levels of more than 50% from enrollment. Secondary endpoints included radiological response, and safety. Results: Of 213 patients with mCRPC screened for HRR mutations, 44 (20.6%) harbored a mutation in the HRR genes. Of these, 39 patients received carboplatin. The baseline characteristics are shown in the table. The primary end-point of PSA50 was observed in 41% patients. Among 30 evaluable patients for radiological responses, partial response occurred in 20.0%, and stable disease in 43.3%. The median duration of response was 6.2 months. In a multivariate analysis, patients with germline mutation were more likely to respond compared to those with somatic mutations (odds ratio, 6.76; P=0.05). Conclusions: In men with mCRPC harboring HRR mutations, carboplatin is associated with 41% PSA50 response rate, suggesting activity in this subset of patients. Patients with germline mutations are more likely to respond to carboplatin. In patients who do not have access to PARP inhibitors, use of carboplatin may be a reasonable option. Clinical trial information: CTRI/2023/04/051507 . Baseline characteristics (n=39). Characteristic Overall (N = 39) Age (years) median [min–max] 65 [52–81] PSA (ng/mL), median [min–max] 48.8 [2.3–1251.0] Family history Yes 11 (28.2%) ECOG Performance Status 0 12 (31.0%) 1 27 (69.0%) Volume* High 33 (84.6%) Low 6 (15.4%) Metastatic sites Non regional Nodal involvement 26 (66.7%) Visceral metastasis 7 (17.9%) Lung metastasis 3 (7.7%) Liver metastasis 5 (12.8%) Skeletal metastasis 37 (94.9%) Pathology (Gleason score) 7 5 (12.8%) 8 18 (46.2%) 9 14 (35.9%) 10 2 (5.1%) Previous therapies Abiraterone acetate (AA) 34 (87.2%) Docetaxel (CSPC) 8 (20.5%) Docetaxel (CRPC) 12 (30.8%) Prior docetaxel (any) 20 (51.3%) Enzalutamide 16 (41.0%) Cabazitaxel 3 (7.7%) Lu-177 PSMA therapy 3 (7.7%) Lines of prior systemic therapies 1 18 (46.2%) 2 15 (38.5%) ≥ 3 6 (15.4%) Mutation type Somatic mutation 23 (59.0%) Germline mutation 16 (41.0%) HRR genes BRCA2 11 (28.2%) ATM 9 (23.1%) BRCA1 6 (15.4%) CDK12 3 (7.7%) RAD54L 3 (7.7%) BRIP1 2 (5.1%) PALB2 2 (5.1%) RAD51D 2 (5.1%) AKT1 1 (2.6%) BARD1 1 (2.6%)

Leukemic stem cells (LSCs) play a critical role in relapse and chemoresistance in acute myeloid leukemia (AML). These LSCs originate from Hematopoietic stem cells (HSCs) after acquiring genetic and molecular aberrations. Both HSCs and LSCs predominantly reside in CD34 +CD38- fraction of the bone marrow and their phenotypic similarities poses a challenge in distinguishing between them. In addition, the phenotypic heterogeneity of LSCs limits the precise quantitation of this population in clinical studies. Delineation of LSCs from HSCs and quantification of LSC burden is crucial as it is correlated with survival rates and treatment outcomes in AML. In this study, we employed single cell transcriptomic analysis to identify differentially expressed cell surface markers that can discriminate LSCs from HSCs. Our data revealed several candidate markers, including CD48, CD52, CD96 and CD88 with distinct expression patterns in LSCs compared to HSCs. We further validated the expression levels of these markers as potential biomarkers for the identification of LSCs in both CD34 + and CD34- AML. Among these cell surface markers, CD52, CD96 and CD48 were significantly over-expressed in LSCs relative to HSCs. Incorporating these markers in combination with established aberrant markers can enhance the identification of LSCs and help distinguish them from HSCs in both CD34 + and CD34- AML. Our findings support the use of an expanded combinatorial marker panel and warrants its further evaluation in a larger AML cohort, particularly in the context of measurable residual disease (MRD) assessment, prognostication and correlation with treatment response and survival outcomes.

Mitophagy is a selective form of autophagy that plays a crucial role in mitochondrial quality control. Mediators of the mitophagy pathway have been reported to contribute to tumor progression in multiple solid tumors. Limited data suggests that the overexpression of certain pathway components may predict for adverse survival outcomes in adult AML. However, the role of these mediators in pediatric AML has not been studied previously. We identified nine mitophagy-related genes (PINK1, PARKIN, SQSTM1, NDP52, OPTN, ULK1, MAP1LC3B, FUNDC1, and BNIP3) using the Reactome pathway database and Ensembl genome browser. Gene expression for each of the nine genes was quantified using quantitative reverse transcription polymerase chain reaction on bone marrow mononuclear cells in a retrospective cohort of 90 children (aged ≤ 18 years) with AML and 30 controls. Differential expression of these genes between patients and controls and across different molecular subtypes was assessed using nonparametric statistical tests. For external validation, transcriptomic data from children and young adults (aged ≤ 39 years) with AML and control samples from the Beat AML cohort were also analyzed. Survival analyses were performed using Kaplan-Meier estimates, and log-rank tests were used to evaluate associations between gene expression (upper versus lower quartiles) and relapse-free and overall survival in our patient cohort. A total of 90 children with AML patients and 30 controls were included. All nine mitophagy-related genes were significantly overexpressed in AML compared with controls, which was independently confirmed in the Beat AML cohort. Upregulation of all nine genes was consistent across most subgroups examined. Among these genes, only FUNDC1 overexpression was significantly associated with inferior relapse-free survival (HR = 2.039, p = 0.044). Mitophagy-related genes are upregulated across pediatric AML subtypes. FUNDC1 expression overexpression is associated with inferior relapse-free survival (RFS). Identifying vulnerabilities in mitophagy pathways may open avenues for therapeutic targeting in pediatric AML.

Leukaemic stem cells (LSCs) are chemo-resistant leukaemia-initiating clones that drive refractoriness and relapse in acute myeloid leukaemia (AML). The study evaluated the prognostic significance of LSC burden in treatment naïve AML patients. LSCs were quantified using Next-generation flow cytometry; patients were stratified into LSCneg/low and LSChigh groups based on the median LSC percentage, and correlated with post-induction morphological remission and measurable residual disease (MRD) status, and long-term outcomes including relapse-free survival (RFS), event-free survival (EFS) and overall survival (OS). LSCs were detectable in 93.5% patients, with a median frequency of 0.386%. Patients with LSCneg/low (≤0.386%) had higher rates of complete remission (CR) (p = 0.05) and MRD negativity (p = 0.002). Lower LSC burden was associated with improved RFS, EFS and OS (all p < 0.05) suggesting the prognostic relevance of LSC quantitation in AML. In both Cluster of Differentiation 34 positve (CD34+) and CD34 negative (CD34-) AML, low LSC% was associated with superior survival outcomes (p < 0.05). LSC burden is a strong, independent predictor of response and survival in AML, and its integration with European LeukemiaNet risk-stratification and MRD assessment may enhance risk refinement and individualized therapy.

Background:Mesenchymal stem cell-based therapy faces challenges that have driven interest in MSCs-derived culture-conditioned media (CCM) as a cell-free alternative. Our study aims to optimize the dose and collection timing of CCM to enhance its therapeutic efficacy in aGVHD, while also standardizing co-culture conditions for CD3+ T-cell interaction with CCM. Material and methods:Human MSCs were isolated from BM and WJ and subsequently preconditioned under hypoxic conditions (1 % O2) for 24 h in a tri-gas incubator. Culture-conditioned media (CCM) were collected from both naive (MSCs) and hypoxia-preconditioned MSCs (MSCsHYP) at 24, 48, and 72 h and filtered using a 0.2 μm membrane filter. CD3+ T-cell were isolated from PBMNCs derived from aGVHD patients. These T-cell were co-cultured at varying densities (2∗106, 5∗106, and 10∗106 cells/ml) with different concentrations of CCM (25 %, 50 %, and 100 %), and cell proliferation was assessed using the MTS assay. Furthermore, CD3+ T-cell proliferation and activation status were evaluated in a 2D co-culture model of CD3+ T-cell and CCM using flow cytometry. Results:Our findings revealed that CCM collected at 48 h, at a 50 % concentration, exerted the most pronounced inhibitory effect on CD3+ T-cell proliferation, particularly at a density of 5∗106 cells/ml, irrespective of the MSCs source. Hypoxia preconditioning significantly enhanced the immunomodulatory effects, with WJ-MSCsHYP-CCM demonstrating superior efficacy in suppressing T-cell proliferation, increasing the CD4+/CD8+ T-cell ratio, and reducing CD4+ T-cell activation compared to BM-MSCsHYP-CCM. Conclusion:These results emphasize the critical role of optimizing CCM collection timing and concentration to maximize therapeutic potential. Our study paves the way for the development of standardized, scalable, and effective cell-free therapies for aGVHD.

We evaluated records of relapse/refractory myeloma patients treated between 2014 and 2019 to assess the efficacy and safety of salvage regimens. One hundred ninety-five patients received salvage therapy, another 61(21.8%) asymptomatic patients with biochemical progression were kept on close follow up. Median PFS was superior for complete responders; 31.2 versus 8.2 months, P < .005. Median PFS for refractory myeloma was 5.09 months compared to 11.4 months for nonrefractory myeloma, P < .001. Median OS was not reached. Background: Treatment of relapse/refractory multiple myeloma (MM) is complex and requires consideration of disease, patients related factors and front-line treatment used. We aimed to assess the efficacy and safety of salvage regimens in symptomatic MM patients. Methods: We evaluated records of relapse/refractory MM patients treated between 2014 and 2019. One hundred ninety-five patients received salvage therapy, another 61 (21.8%) asymptomatic patients with biochemical progression were kept on close follow up. Primary outcome was progression free survival (PFS). Response and toxicity to treatment and overall survival (OS) were secondary outcome measures. Results: Patients median age was 59.5 years (range; 23-84 years) and 65.7% were males. Among 176 (90.3%) evaluable patients; 98(55.6%) responded; complete response (CR)-19(10.8%), very good partial response (VGPR)-14(7.9%), and partial response (PR) 65(36.9%). Median PFS was superior for complete responders; 31.2 versus 8.2 months, P < .005. Median PFS for refractory myeloma was 5.09 months compared to 11.4 months for nonrefractory myeloma, P < .001. Median PFS was 6.70 months for those with clinical relapse versus 9.50 months for biochemical relapse ( P = .62). Median OS was not reached. Circulating plasma cells > 5%, thrombocytopenia, refractory disease were predictors of inferior PFS. Most common grade 3/4 treatment-related adverse events were thrombocytopenia (5.7%), anemia (7.5%), and febrile neutropenia (5.2%). About 10(2.4%) patients required change of therapy due to adverse reactions. Conclusion: Achievement of CR in symptomatic, relapsed myeloma was associated with superior PFS. Careful observation for asymptomatic patients with biochemical relapse is a reasonable approach. Newer novel molecules for those with refractory disease are needed.

There is dearth of clinical data from India regarding outcomes of umbilical cord blood transplant (UCBT). This study aimed to analyze the long-term outcomes in children who underwent UCBT at a single Indian center. This retrospective study included patients who underwent UCBT between 2011 and 2024 in a tertiary care center in Northern India. Data on HLA-matching, cell dose, conditioning, engraftment, toxicities and survival outcomes were recorded. Out of 20 patients with median (Q1, Q3) age 4 (2, 6) years, 11 had leukemia and 9 had immunodeficiencies or enzymopathies. Majority (90

Mesenchymal Stem Cells-derived Small Extracellular Vesicles endowed with regenerative cargo from their parent cells, have emerged as a promising avenue for cell-free therapeutics in regenerative medicine. Notably, deliberate induction of apoptosis in MSCs before sEV isolation has been identified as a strategy to augment the regenerative capabilities of MSCs-sEVs. This study explores a novel approach to enhance the immunomodulatory potential of MSC-sEVs through apoptosis induction and optimal tissue source to ensure consistent and improved clinical outcomes. Apoptosis was induced in tissue-specific MSCs using Staurosporine. sEVsV and sEVsApo were isolated via ultracentrifugation. Invitro immune response was assessed via T-cell proliferation, T-regulatory cell induction macrophage polarization assay. Mitochondrial bioenergetics was studied using MitoSOX staining and Seahorse assay in H2O2-treated HuH7 cells. These findings were validated invivo in the CCL4-induced Chronic Liver Disease model via Histopathological staining, biochemical parameters, and fibrotic, pro-inflammatory, and anti-inflammatory markers and assessed the mechanism by targeting TGF-β/SMAD pathway. Our results demonstrate that sEVsApo exhibited significantly higher concentrations and superior immunomodulatory effects by suppressing CD3 + T-cell proliferation, promoting T-regulatory cell differentiation, and polarized macrophages towards M2-phenotype. In terms of tissue specificity, it was observed that WJ-sEVs were faring better. sEVsApo effectively reduced mitochondrial ROS significantly improved oxidative phosphorylation. Invitro findings were corroborated in an invivo CLD model, wherein sEVsApo ameliorated fibrosis and inflammation, by inhibiting TGF-β/ SMAD2/3 pathway. This study concludes that apoptosis induction can be considered as minimum manipulation strategy to enhance the immunoregulatory and regenerative potential of MSCs-sEVs, thereby expanding their implication in immune disorder.

BACKGROUND:Radioactive iodine (RAI) therapy is the standard-of-care for metastatic differentiated thyroid cancer (DTC), but ~60% of patients show resistance before achieving satisfactory response. METHODS:Eligible patients were randomly assigned to RAI therapy plus lenvatinib (RAI-L arm) or standard RAI therapy alone (RAI arm). All patients were administered RAI therapy (5.5-7.4 GBq) every 6-9 months, and patients in RAI-L arm were additionally administered lenvatinib (10 mg once daily). The primary endpoint was objective response rate (ORR). Secondary endpoints included progression-free survival (PFS), overall survival, quality of life, and toxicity. RESULTS:Fifty patients were enrolled (mean age 49.1±12.6 y, range 21-67). ORR was significantly higher in the RAI-L arm compared with RAI arm (54.5% vs. 24%; P =0.03). Subgroup analysis indicated combination therapy was more beneficial in age older than or equal to 55 years ( P =0.04), follicular thyroid carcinoma ( P =0.04), presence of both pulmonary and extra-pulmonary metastases ( P =0.007), and RAI therapy-naive ( P =0.02) patients. Median PFS in the RAI-L arm was 36 months (95% CI: 24.5-47.5) versus 26 months (95% CI: 18.9-33.1) in the RAI arm ( P =0.09). Grade ≥3 adverse events were more frequent in the RAI-L arm (45.5%) compared with RAI arm (8%, P =0.006), with hypertension (31.8%) and hand-foot skin reaction (13.6%) being the most common. CONCLUSIONS:Combining RAI therapy with lenvatinib improved ORR with clinically meaningful prolongation of PFS; however, it comes with a burden of treatment-related toxicity, underscoring the need for careful patient selection.

BACKGROUND:Measurable residual disease (MRD) is becoming a cornerstone in the multiple myeloma (MM) management; however, its implementation in India faces several challenges. This Delphi survey aimed to gather expert consensus on the current practices, and barriers in MRD monitoring in MM in India. METHODS:A 3-round Delphi process (2 e-surveys and 1 in-person meeting) was conducted with hematologists, pathologists, and oncologists managing MM in India. Consensus (≥ 75% agreement) led to recommendations for standardized MRD practices. RESULTS:Twenty-five experts participated, agreeing on key protocols: processing first-pull bone marrow aspirates within 24 hours, using a single tube with at least a 10-color panel, acquiring at least 3 million events for 10⁻⁵ sensitivity under proper environmental control, and by adequately trained staff. At least 4 monoclonal antibodies for gating of plasma cells and at least 3 parameters among mast cells, myeloid precursors, hematogones, normal plasma cells, should be used to assess hemodilution. Guidance on modulation of treatment decisions, including maintenance therapy based on MRD status remains inconclusive. Though, there is an agreement that MRD negativity in MM improves survival and lowers relapse risk but currently it does not influence maintenance therapy decisions. MRD testing was advised at postinduction, pre/post-transplant, and annually during maintenance. Challenges identified included protocol variability, interpretation issues, and lack of an external quality assessment program. Experts emphasized the need for advanced flow cytometry training. CONCLUSIONS:The findings of this study will guide clinical adoption and future research, particularly for high-risk populations and novel therapies.

Background The toxicity associated with conventional conditioning regimens limits treatment outcomes in autoimmune disorders such as acute graft-versus-host disease (aGVHD). Developing effective adjunctive interventions to restore immune balance is therefore essential. This study investigated the immunomodulatory potential of mesenchymal stem cells (MSCs)-derived culture-conditioned media (CCM) from naïve and preconditioned MSCs-hypoxic (MSCsHYP), apoptotic (MSCsAPO), and dual preconditioned (MSCsHYP+APO) in aGVHD. Methods Human MSCs isolated from bone marrow and Wharton’s Jelly were preconditioned under hypoxia (1% O₂), apoptosis (1 µM staurosporine, 24 h), or both. The immunoregulatory and antioxidant properties of their CCM were evaluated through T-cell proliferation assays, Treg induction, macrophage polarization, mitochondrial function, and T-cell bioenergetics. Comparative proteomic profiling of CCM from WJ-MSCs and WJ-MSCsHYP+APO co-cultured with aGVHD patient-derived activated PBMNCs was performed using LC-MS/MS, alongside in vivo validation in a chemotherapy-induced aGVHD murine model. Results WJ-MSCsHYP+APO-CCM exhibited superior immunomodulatory efficacy, suppressing T-cell proliferation, promoting Treg and Th2/Th9 differentiation, and driving M2 macrophage polarization. It reduced mitochondrial ROS, enhanced mitochondrial polarization, and shifted T-cell metabolism from glycolysis toward oxidative phosphorylation. Proteomic analysis revealed modulation of IL-12, IL-17, and JAK–STAT pathways, along with regulation of complement, coagulation, and metabolic cascades. Interaction with immune cells further enhanced its antioxidant and tissue-reparative properties via extracellular matrix remodeling. Conclusion Dual preconditioning under hypoxia and apoptosis amplifies the immunomodulatory, antioxidant, and reparative efficacy of WJ-MSC-CCM, offering a potent non-cellular therapeutic strategy for aGVHD management. GRAPHICAL ABSTRACT Immunomodulatory and immune metabolic reprogramming potential of naïve and preconditioned MSCs (MSCs, MSCsHYP, MSCsAPO, MSCsHYP+APO) derived CCM in Acute GVHD (created using [Biorender.com][1]) ![Figure][2] ### Competing Interest Statement The authors have declared no competing interest. Indian Council of Medical Research, https://ror.org/0492wrx28, 2021/14763 [1]: https://Biorender.com [2]: pending:yes

Background/Objectives: AML is a heterogeneous hematological malignancy distinguished by the clonal expansion of immature myeloid progenitor cells. Despite advances in therapy, relapse rates remain high, and outcomes are poor. The WT1 gene has emerged as a potential contributor to leukemogenesis, but its clinical relevance at the transcriptional level is not fully understood. This study employed RNA sequencing as a discovery tool to identify WT1 gene expression in AML and further investigated its role in diagnosis, prognosis, and treatment response. Methods: Between 2020 and 2024, 345 diagnostic, 259 post-induction, and 70 relapse-stage BM or PB samples were prospectively collected from de novo AML patients at AIIMS, New Delhi. RNA sequencing was initially performed on five paired diagnosis-relapse samples to profile transcriptomic changes and assess WT1 expression dynamics. WT1 expression was further validated by qPCR. The relationship between WT1 expression and various clinical parameters was evaluated using Cox regression analysis to determine its impact on prognosis. Results: RNA sequencing and qPCR confirmed WT1 overexpression at diagnosis, which significantly declined following induction therapy. High WT1 expression at diagnosis was linked with adverse clinical characteristics, including elevated WBC counts and higher blast percentages and predicted poor survival outcomes. WT1 expression was identified as a significant prognostic marker, correlating with OS and EFS. Conclusions: By integrating RNA sequencing with targeted validation, this study highlights WT1 expression as a critical biomarker for AML diagnosis, prognosis, and treatment response. The findings suggest that WT1 expression may serve as a valuable tool for monitoring disease status, risk stratification, and guiding treatment decisions in AML, with potential applications for WT1-targeted precision therapies.