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Dissecting the heterogeneity of IGHV-mutated CLL: An eric study.
No full textIntroduction: Patients with CLL and mutated immunoglobulin heavy variable (IGHV) genes (M-CLL) are clinically heterogeneous. While genomic aberrations contribute to adverse outcomes in certain M-CLL subgroups, they do not fully account for M-CLL heterogeneity, suggesting the need for further research.
Methods: This is a retrospective, observational study aiming to identify factors associated with shorter overall survival (OS) after first-line (1L) treatment in M-CLL. The study included patients diagnosed with M-CLL between 2000-2022 in 26 centers with a follow-up >6 months after 1L treatment. Special attention was given to immunogenetic features, including BcR stereotypy. Besides, we developed a novel immunogenetic metric that considers the amino acid composition of the germline IGHV genes, following the IMGT physicochemical classification table. Each aligned position across the IGHV gene sequences was assigned different scores based on the relation between the assessed amino acids: 0 if identical, 1 if in the same physicochemical group, and 2 if in different groups. This scoring system enabled the generation of a distance matrix for all IGHV genes, which was then used as input for hierarchical clustering, leading to the creation of 15 clusters. Univariable (UVA) and multivariable (MVA) analyses were performed to identify risk factors associated with shorter OS. The variables assessed in the UVA were age at 1L initiation, biological sex, type of 1L treatment, TP53 mutations, FISH aberrations, and karyotype.
Results: 1933 patients from 26 centers in 12 countries were evaluated. The median age at 1L treatment was 69 years (IQR: 62-76). Most patients were males (1184, 61.3%) and 1249 (64.7%) were alive at last follow up. The median follow-up from 1L treatment was 4.6 years (IQR: 1.8-8.1). Before 1L treatment, 623/1090 (57.2%), 195/1077 (18.1%), 107/1342 (8%) and 103/1240 (8.3%) carried del(13q), trisomy 12, del(17p) and del(11q) detected by FISH, respectively. TP53 mutations were detected in 118/1012 (11.7%) cases and karyotype with ≥3 and ≥5 (CK5) aberrations in 82/610 (13.4%) and 17/610 (2.8%) cases, respectively. The most common stereotyped subsets were #2 (59/1112, 5.3%) and #4 (11/1112, 1%). Most patients (1346, 69.8%) received 1 line of treatment, while 344 (17.8%), 138 (7.2%) and 101 (5.2%) received 2, 3, and ≥4 lines, respectively. FCR was the most common 1L treatment (395, 20.8%) followed by chlorambucil (Chl) monotherapy (320, 16.9%). BTK inhibitors (BTKis) were used in 241 cases [12.5%; ibrutinib: 162 (8.3%), acalabrutinib 65 (3.4%), zanubrutinib: 10 (0.5%), pirtobrutinib 4 (0.2%)]. BR, Chl-rituximab and Chl-obinutuzumab were used in 185 (9.8%), 126 (6.6%) and 98 (5.2%) cases, respectively. Finally, 70 (3.6%) received venetoclax-obinutuzumab 1L treatment and 33 (1.7%) received ibrutinib-venetoclax. The median OS was 11 years (95% CI: 10.4-11.8). In UVA, older age at 1L, male sex, TP53 aberrations (TP53-abs), del(11q) and CK5 were associated with shorter OS (p<0.001, p=0.03, p<0.001, p<0.001, p=0.001, respectively). Compared to FCR/BR, targeted treatments led to a similar OS (p=0.3), while other non-targeted treatments resulted in shorter OS (p<0.001). Regarding the new immunogenetic metric, clusters 13 (IGHV1-24 and IGHV1-69-2 genes), 4 (IGHV2 genes) and 8 (IGHV3-13) associated with shorter OS (p=0.07, p=0.02, and p=0.002, respectively). To assess the relevance of this finding, we scanned our immunogenetic database consisting of 42,154 M-CLL IG rearrangements. While the IGHV1-24, IGHV1-69-2 and IGHV3-13 genes were very rare (0.6%), IGHV2 gene rearrangements represented a sizeable M-CLL subgroup (1969 cases, 4.7%). In MVA, only age at 1L and CK5 retained statistical significance for OS (HR: 1.08, 95% CI: 1.04-1.3, p<0.001, HR: 2.5, 95% CI: 1.04-6.2, p=0.04, respectively).
In patients <70 years, older age at 1L, TP53-abs, del(11q), and clusters 4 and 8 were associated with shorter OS (p<0.001, p=0.01, p=0.007, p=0.01, and p=0.01, respectively). The type of treatment effect was similar to the whole cohort. In MVA, age at 1L andTP53-absretained statistical significance (HR:1.07, 95% CI:1.02-1.11, p=0.003, HR:1.9, 95% CI:1.02-3.5, p=0.04, respectively).
Conclusion: Older age, CK5 and TP53 aberrations are independent high-risk factors for shorter OS in M-CLL. Utilization of IGHV2 subgroup genes emerged as adverse-prognostic for OS and merits further evaluation
IBCL-618: Perspective on marginal zone lymphoma in India
No full textContext:
Marginal zone lymphomas (MZL) are indolent non-Hodgkin lymphomas (NHL), representing 7% to 17% of NHL cases in Western nations. MZL consists of three subtypes: extranodal mucosa-associated lymphoid tissue (MALT lymphoma), nodal MZL, and splenic MZL.
Objective:
Data on the incidence and prognosis of MZL in patients from India are nonexistent.
Design, Setting, and Participants
This retrospective study aims to examine patients who were diagnosed with NHL and were registered at the Department of Medical Oncology, AIIMS, New Delhi. There were 1,800 confirmed cases of NHL in adults (individuals ≥18 years) between 2014 and 2023. Data on baseline features, therapy, and survival were extracted from patient medical records. Active surveillance, antibiotic monotherapy, radiotherapy, single-agent rituximab, or rituximab plus chemotherapy were the recommended treatments.
Results:
Out of all NHL cases, 54 (3%) were classified as MZL. The cohort comprised 33 males and 21 females, with a median age of 59 years (range: 21–89 years). MALT accounted for 30 cases (56%), splenic MZL for 14 cases (26%), and NMZL for 10 cases (19%)—representing the three most prevalent subtypes. Moreover, 6 individuals (11%) exhibited elevated LDH levels. The gastric region represented 60% of MALT lymphoma cases, followed by the ophthalmic area at 20%, and the parotid gland at 10%; of the remaining cases, 4 were associated with the intestinal region and 1 each for breast, lung, skin, and brain. In the follow-up, 42.5% of patients received chemo-immunotherapy, comprising bendamustine and rituximab; 7.4% were treated with single-agent rituximab; 21% underwent radiation therapy; and nearly 33% remained under close observation. Approximately 63% of the cases underwent combined modality treatment, which included antibiotics, radiation, chemoimmunotherapy, or SA rituximab. The response rate following treatment was 83%. Within the entire cohort, 7.4% exhibited transformed high-grade lymphoma. At a median follow-up of 40 months, the event-free survival was 72.1%, while the overall survival rate was 85.4%.
Conclusion:
MZL represents 3% of the total NHL. Extranodal marginal zone lymphoma (ENMZL) was the most prevalent, followed by splenic MZL. The response rate and outcome were consistent with existing literature
IBCL-293: Outcomes of follicular lymphoma patients treated with a uniform protocol: A single-institution analysis
No full textBackground:
Follicular lymphoma (FL) is the second most common subtype of non-Hodgkin lymphoma (NHL) in India. Bendamustine-rituximab (BR) is a widely adopted regimen for treatment-naive FL. However, limited data exist from Indian cohorts regarding survival outcomes with this approach. This study evaluates the clinical characteristics, treatment outcomes, and prognostic factors of FL patients treated with the BR regimen at a single tertiary care center.
Methods:
This retrospective study included 107 patients diagnosed with FL and registered at our institution between 2012 and 2023. Among these, 64 patients were uniformly treated with 6 cycles of the BR regimen, with or without rituximab maintenance therapy.
Results:
Of the 64 patients, 37 were male and 27 were female, with a median age of 52 years (range, 27–70). The Ann Arbor stage distribution was as follows: stage 1 (2%), stage 2 (6%), stage 3 (20%), and stage 4 (72%). Bone marrow involvement and bulky disease were observed in 41% and 33% of patients, respectively, while extra nodal involvement occurred in 77%. Based on the Follicular Lymphoma International Prognostic Index (FLIPI-1), 11% were low risk, 23% intermediate risk, and 66% high risk. Rituximab maintenance therapy was administered to 32 patients (50%), with financial constraints being a key limiting factor. The overall response rate (ORR) was 89%, and complete remission (CR) was achieved in 75% of patients. During follow-up, two patients experienced transformation to diffuse large B-cell lymphoma (DLBCL). At a median follow-up of 60 months, the median overall survival (OS) was not reached. PFS rates were 87.3% at 12 months (95% CI, 79.5%–95.9%) and 67.7% at 60 months (95% CI, 55.6%–82.3%), demonstrating sustained long-term efficacy of the BR regimen. The most common toxicities included skin rash (13%) and febrile neutropenia (10%). All-grade toxicities were observed in 34% of patients. Maintenance rituximab was significantly associated with better progression-free survival (PFS) (adjusted hazard ratio [aHR], 0.23; 95% CI, 0.08–0.64), while no other clinical or tumor characteristics correlated with survival outcomes.
Conclusion:
This study highlights the favorable efficacy and manageable toxicity profile of the BR regimen in treatment-naive FL patients. Rituximab maintenance therapy after induction immunochemotherapy improves PFS
Application of targeted RNA‐sequencing in high‐risk B‐ cell acute lymphoblastic leukemia (B‐ALL): Identifying fusions, IKZF1 deletions, and CRLF2 expression in an Indian cohort
No full textIntroduction
B-cell acute lymphoblastic leukemia (B-ALL) is genetically heterogeneous. We assessed the utility of FusionPlex ALL targeted RNA sequencing panel in detecting gene fusions and other genomic lesions in B-ALL.
Methods
The high-risk B-ALL, negative for common recurrent gene fusions (RGF), that is, BCR::ABL1, ETV6::RUNX1, TCF3::PBX1 and KMT2A::AFF1, were analysed with RNA-based targeted sequencing 81-gene-panel FusionPlex ALL (IDT, USA). Multiplex ligation-dependent probe amplification (MLPA) was used for IKZF1 deletions and flow-cytometry for CRLF2 expression and ploidy analysis.
Results
Out of 32 samples, 27 were high-risk B-ALL cases (median age 16 (1–41) years) and 5 B-ALL controls with known fusions for validation. The fusions were detected in 6/27 (22%) RGF-negative B-ALL cases; 2 with EPOR::IGH and 1 each P2RY8::IGH, PAX5::ETV6, SNX2::ABL1, IKZF1::CIITA. In addition, IKZF1 and/or PAX5 gene deletions resulting in the formation of oncogenic/novel isoforms were detected in 75% (15/20) samples positive on MLPA. Flow-cytometry CRLF2 overexpression was noted in 60% (9/15) tested samples which correlated well with targeted RNAseq CRLF2 gene expression.
Conclusion
The targeted sequencing approach can help in detecting known and novel fusions in B-ALL, novel breakpoints in the known fusions, gene deletions as oncogenic/novel isoforms and CRLF2 expression
The role of background matching and disruptive coloration in impeding detection and recognition
No full textCamouflage involves diverse strategies that aid animals in obscuring their presence from potential threats. These strategies inhibit detection (locating the animal) and, if detected, prevent recognition (determining the animal’s identity) of the bearer. Background matching, where animals have color patterns that match the appearance of the background they are viewed against, and disruptive coloration, where animals have high contrast markings that hinder the perception of their shape, are two of the most ubiquitous camouflage strategies. While the effect of background matching and disruptive coloration in impeding detection has been extensively studied, their effect on recognition remains poorly understood, with many studies implicitly assuming that patterns hindering detection also inhibit recognition. Here, using human volunteers as ‘predators’ of virtual targets, we tested the effectiveness of background matching and disruptive coloration on detection and recognition. We demonstrate that detection and recognition are not fully coupled because patterns effective at hindering detection did not necessarily impede recognition, and conversely, patterns that inhibited recognition were not always effective at preventing detection. The extent of background matching influenced both detection and recognition. However, the immediate match between the target’s outline and its background had a greater impact on recognition than the overall background match. Furthermore, disruptive patterns that did not break the outline of the target outperformed patterns that broke up the outline in terms of detection under certain situations. Our findings highlight that camouflage can act independently on detection and recognition, and underscore the importance of recognition in studies of animal camouflage
Oviposition Colour Preferences in a Grass‐Feeding Butterfly
No full textHerbivorous insects use both visual and chemical cues to locate suitable host plants in diverse vegetation. Because colour is among the most salient visual cues, such insects are expected to have preferences for particular colours when searching for host plants. To test whether colour preferences play a role during host-plant selection, we performed a series of oviposition-choice experiments on common evening brown butterflies (Melanitis leda L.; Lepidoptera: Nymphalidae) using artificial grasses. This species uses a wide variety of grasses as host plants but nevertheless shows strong preferences among species of grass. We determined preferences between primary colours (red, blue and green), and preferences between greens that vary in (a) brightness (luminance), (b) hue (adding some blue or green) and (c) saturation (adding various amounts of grey). We found that these butterflies readily oviposited on artificial grass and responded to hue, brightness and saturation. They appeared to prefer bright green, pure green or slightly red-shifted green, and green of high saturation. The acceptance of artificial grass shows that visual cues, possibly together with mechanical cues, can be enough to induce oviposition behaviour. The preferences appear to fit with the host-plant use of this species. Our results highlight the importance of visual cues for ovipositing insects
Piezoelectricity in a mixture of chiral 1D hybrid lead bromide and iodide systems
No full textChiral organic–inorganic hybrid perovskites possess inherent structural asymmetry and lattice flexibility, enabling a piezoelectric response suitable for energy harvesting and sensing technologies. Here, we introduced a new strategy for the development of a piezoelectric nanogenerator (PENG) constructed from a mixture of two chiral one-dimensional hybrid lead halides, (R-MBA)PbBr3 and (R-MBA)PbI3 (MBA: methylbenzylammonium). Individually, both hybrid halide systems exhibit piezoelectric behaviour, but when mixed, the piezoelectric output increases significantly. The highest performance is achieved for the optimized mixed halide mixture [75 wt% (R-MBA)PbBr3 + 25 wt% (R-MBA)PbI3]. To improve flexibility and mechanical endurance, we incorporated the optimized halide mixture into a polycaprolactone (PCL) polymer matrix. The device with 15 wt% of the optimized halide mixture embedded in PCL demonstrates the highest peak-to-peak voltage of 40.8 V with a power density of 83.1 μW cm-2. The halide mixture–PCL composite significantly enhances the device performance, facilitated by its endurance to a higher impact force of 21 N at 8 Hz compared to the neat mixture of hybrid halide salts without PCL (4 N at 6 Hz), leading to a 1.5 times enhancement in the peak-to-peak voltage. Finally, self-powered pressure sensors were fabricated by integrating multiple PENG devices and demonstrated for smart door mat applications. These findings show that physical mixing of chiral hybrid lead halides might be a useful approach to enhance piezoelectric performance
Remote sensing of biodiversity and climate change: adaptation and mitigation prospective
No full textThe vital role of biodiversity cannot be ignored in the context of changing climate as its critical role in affecting the key ecological processes, that is, productivity, regulation of climate and hydrological cycle, maintenance of atmosphere, water, and soil fertility, are determinants of ecosystem health. In this regard, plant diversity plays a major and dominant role in providing niches to other biota. Additionally, climate change has become a significant new threat imposing increasingly higher risks of extinction with an increase of 2°C–3°C temperature above preindustrial level. Thus more robust and meaningful research on biodiversity especially on plant diversity in response to various drivers must be carried out to analyze their geographic pattern and response toward the climate change scenario to formalize most suitable conservation prioritization along with their sustainable use. Most of the essential indicators for biodiversity monitoring can be derived from remotely sensed imageries. Researchers are using high resolution earth observation data to derive environmental heterogeneity parameters useful to study biodiversity and climate change. Considering the prevailing climate change scenario, modeling approaches and understanding of environmental variability along with multi-scale approaches, the advances in understanding can enhance the biodiversity conservation measures. This chapter also discusses on the adaptation and mitigation strategies which help maintain ecosystem resilience. The importance of global collaboration and local actions in tackling biodiversity and climate challenges, offering solutions that align with the sustainable development goals (SDGs) 13 (Climate Action) and 15 (Life on Land) are discussed
Naphthalimide-based fluorescent polymeric probe: a dual-phase sensor for formaldehyde detection.
No full textFormaldehyde (FA) is a common pollutant found indoors and outdoors, posing a significant threat to human health. Therefore, developing sensitive and efficient detection methods for FA is essential for environmental monitoring and protecting public health. Herein, we report a naphthalimide-conjugated water-soluble polymeric fluorescent probe for the detection of FA in both aqueous and vapor phases using fluorimetric methods. The aromatic amines present in the side chain of the polymer react with FA, forming a Schiff base (imine bond). This imine formation inhibits the photoinduced electron transfer (PET) process within the polymer, leading to a ‘turn-on’ fluorescence under 365 nm UV light. The probe is capable of selectively sensing FA with a detection limit as low as 1.36 nM in aqueous medium. The formation of imine is confirmed for the model reaction between 6-(4-aminophenyl)-2-(4-((4-vinylbenzyl)oxy)phenyl)-1 h-benzo[de]isoquinoline-1,3(2 h)-dione and FA by electrospray ionization mass spectrometry (ESI-MS) and nuclear magnetic resonance (NMR) titration methods. The mechanism behind ‘turn-on’ FA sensing is investigated using density functional theory (DFT) analysis. Additionally, the study demonstrates a facile approach for covalently attaching the polymer on the surface of a filter paper surface via ultraviolet (UV) light-induced cross-linking. Such polymer attached paper exhibits FA vapor sensing through changes in fluorescence intensity
Pediatric mature B-cell non-hodgkin lymphoma in India: A retrospective multicenter pooled analysis of treatment approaches and outcomes
No full textBackground
Published data on outcomes of pediatric mature B-cell non-Hodgkin lymphoma (B-NHL) from India is limited and difficult to interpret due to small sample size and non-uniform treatment protocols. This study aims to do a pooled analysis of published patient data from multiple centers across India to provide a clearer understanding of survival rates and treatment-related toxicities with respect to the treatment protocols in this population.
Methods
A pooled analysis was conducted of patient data from 505 children with mature B-NHL, including Burkitt lymphoma (n = 395), diffuse large B-cell lymphoma (DLBCL, n = 52), and other subtypes (n = 58), treated from 2000 to 2022 at seven major cancer centers in India. Outcomes assessed were grade 3/4 toxicities, toxic deaths, relapse/progression, and survival rates.
Results
Most patients (401/505) presented with advanced disease; bone marrow and CNS involvement were observed in 13.9 % and 6.9 % of cases, respectively. Treatment protocols primarily included LMB (n = 208), BFM (n = 191), and MCP (n = 61). Grade 3/4 toxicities were reported in 79.2 % of patients, with higher rates observed with LMB protocol (92.1 %) compared to BFM (70.8 %) and MCP (70.1 %) (p < 0.001). Toxic death rates were similar across protocols. Overall survival (OS) and event-free survival (EFS) at a median follow-up of 17 months were 69.4 ± 2.2 % and 64.9 ± 2.2 %, respectively, with no significant differences in relapse/progression rates or stage-specific OS between protocols (p = 0.28 and 0.51).
Conclusions
This pooled analysis shows that although treatment-related toxicities differ by protocol, overall survival outcomes were similar across the LMB, BFM, and MCP regimens, despite being much lower than those reported from high income countries. Uniform standardized protocols may further improve outcomes for pediatric B-NHL in India