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Background: Asparaginase-associated pancreatitis (AAP) is a major challenge for continuing asparaginase therapy. We aimed to investigate the acute and longterm complications and survival rates related to first and second AAP episodes in Chinese children with haematological malignancies. Methods: We retrospectively analysed clinical data of children with pancreatitis who received asparaginase chemotherapy for acute lymphoblastic leukaemia (ALL), acute mixed cell leukaemia, and non-Hodgkin's lymphoma at Shanghai Children's Medical Center from November 2013 to November 2023. Results: Of the 76 children included in the study, 12 had local complications (15.79%), with no deaths recorded. Systemic complications manifested in 28 patients (36.84%), resulting in 3 deaths (3.95%). Four patients (5.26%) developed long-term complications (chronic pancreatitis or insulin-dependent diabetes mellitus). No significant differences in local or long-term complications were recorded between children in the asparaginase re-exposed (n=39) and non-reexposed (n=45) groups. Among the re-exposed patients, eight (25.81%) experienced a second attack without fatalities or complications. Survival analysis of intermediate-to high-risk patients revealed a significantly higher event-free survival (EFS) rate for the re-exposed group than for the non-reexposed group. The second AAP episode's occurrence and severity had no relation to the first AAP episode's severity, and the second AAP episode was significantly less severe than the first (p<0.001). Conclusions: The second AAP episode's occurrence is unrelated to the first AAP episode's severity, and the second AAP episode's severity is significantly lower than that of the first. Further, asparaginase therapy could improve EFS in children with intermediate and high-risk ALL. [ABSTRACT FROM AUTHOR]

Leukaemic optic neuropathy is an uncommon cause of visual loss which represents a neuro-oncological emergency with the potential of irreversible blindness if untreated. It can be difficult to diagnose, often presenting with normal neuroradiological and cerebrospinal fluid findings. We present the case of a 26-year-old woman with T-cell acute lymphoblastic leukaemia with optic neuropathy secondary to leukaemic infiltration, who demonstrated features on optical coherence tomography that aided the diagnosis of this condition. This included the presence of numerous, small, hyperreflective opacities erupting from the optic nerve head, which improved following treatment with radiotherapy and chemotherapy, and later recurred when the condition relapsed. This finding may help clinicians differentiate between other causes of optic neuropathy as well as assessing response to treatment and monitoring for recurrence. [ABSTRACT FROM AUTHOR]

Acute lymphoblastic leukaemia (ALL) is one of the most common types of childhood cancer. Treatment of ALL may involve using the enzyme L-asparaginase (ASNase) from Escherichia coli as the first option. However, native E. coli ASNase can induce the production of antibodies, interfering with its pharmacological activity and increasing the risk of allergic reactions. Therefore, monitoring the production of anti-ASNase antibodies in patients is essential for determining treatment efficacy. Hence, a simple, precise, and selective method for the measurement of antibodies is of great interest. In this context, this work reports on an electrochemical biosensor based on carbon-printed electrodes to quantify antibodies in ALL patients under treatment using an ASNase-based protocol. For selective detection of anti-ASNase antibodies, ASNase was immobilized on electrodes using the nanocomposite Fe3O4/chitosan. The biosensor showed linearity for the antibody concentrations between 0.1 and 10 µg mL−1, with a limit of detection of 150 ng L−1. In addition, the biosensor was selective and provided reproducible results with a variability of 3.3%. From these results, it was concluded that the biosensor presented here is a promising device for the measurement of anti-ASNase antibodies produced in patients under treatment for ALL. [ABSTRACT FROM AUTHOR]

Prolonged exposure to hydroquinone (HQ), a metabolite of benzene, can cause severe haematologic disorders in humans. However, the mechanism is still unclear. In the present study, we investigated whether HQ can induce haematological diseases through ferroptosis, which is another form of cell death apart from apoptosis. The results showed that HQ inhibited the viability of Jurkat cells in a dose-dependent and time-dependent manner. The half inhibitory concentrations (IC50s) of HQ-treated Jurkat cells for 12 h, 24 h and 48 h were 107.16 μmol/L, 33.29 μmol/L, and 14.78 μmol/L. The exposure of Jurkat cells to HQ increased intracellular Fe 2 + , malondialdehyde (MDA) and lipid reactive oxygen species (ROS) levels and down-regulated glutathione (GSH) levels. We used erastin-treated cells as a positive control and cells treated with HQ combined with deferoxamine mesylate (DFO) and ferrostain-1 (Fer-1)-treated cells as the negative controls. DFO and Fer-1 partially restored the degradation of cell viability and GSH content and the accumulation of Fe 2 + , MDA and lipid ROS caused by HQ. In addition, we found that cellular mitochondria in the HQ-treated group showed a decrease in volume, an increase in the density of the bilayer membrane and a decrease or disappearance of mitochondrial cristae. Changes in the erastin-treated group were similar to those in the HQ-treated group. We inferred that HQ induces ferroptosis in Jurkat cells. Subsequently, we found that HQ up-regulated the levels of transferrin receptor 1 (TFRC) mRNA and protein expression and down-regulated FTH1, SLC7A11 and synthetic substrate of antioxidant enzyme 4 (GPX4) mRNA levels and protein expression levels. However, the exposure of Jurkat cells to HQ with DFO and Fer-1 alleviated these changes. Notably, the activation of TFRC and the inhibition of FTH1 and System X c − (cystine–glutamate reverse transporter protein) /GPX4 were associated with HQ-induced ferroptosis. These results provide novel insights into how HQ exacerbates haematopoietic cytotoxicity and provide potential targets for the prevention of HQ-induced diseases. [ABSTRACT FROM AUTHOR]

Mesenchymal stem cells (MSCs) are one of the main residents in the bone marrow (BM) and have an essential role in the regulation of haematopoietic stem cell (HSC) differentiation and proliferation. Myelodysplastic syndromes (MDSs) are a group of myeloid disorders impacting haematopoietic stem and progenitor cells (HSCPs) that are characterised by BM failure, ineffective haematopoiesis, cytopenia, and a high risk of transformation through the expansion of MDS clones together with additional genetic defects. It has been indicated that MSCs play anti-tumorigenic roles such as in cell cycle arrest and pro-tumorigenic roles including the induction of metastasis in MDS and leukaemia. Growing evidence has shown that MSCs have impaired functions in MDS, such as decreased proliferation capacity, differentiation ability, haematopoiesis support, and immunomodulation function and increased inflammatory alterations within the BM through some intracellular pathways such as Notch and Wnt and extracellular modulators abnormally secreted by MSCs, including increased expression of inflammatory factors and decreased expression of haematopoietic factors, contributing to the development and progression of MDSs. Therefore, MSCs can be targeted for the treatment of MDSs and leukaemia. However, it remains unclear what drives MSCs to behave abnormally. In this review, dysregulations in MSCs and their contributions to myeloid haematological malignancies will be discussed. [ABSTRACT FROM AUTHOR]

The evolution of cancer treatment has provided increasingly targeted strategies both in the upfront and relapsed disease settings. Small‐molecule inhibitors and immunotherapy have risen to prominence with chimeric antigen receptor T‐cells, checkpoint inhibitors, kinase inhibitors, and monoclonal antibody therapies being deployed across a range of solid organ and haematological malignancies. However, novel approaches are required to target transcription factors and oncogenic fusion proteins that are central to cancer biology and have generally eluded successful drug development. Thalidomide analogues causing protein degradation have been a cornerstone of treatment in multiple myeloma, but a lack of in‐depth mechanistic understanding initially limited progress in the field. When the protein cereblon (CRBN) was found to mediate thalidomide analogues' action and CRBN's neo‐targets were identified, existing and novel drug development accelerated, with applications outside multiple myeloma, including non‐Hodgkin's lymphoma, myelodysplastic syndrome, and acute leukaemias. Critically, transcription factors were the first canonical targets described. In addition to broadening the application of protein‐degrading drugs, resistance mechanisms are being overcome and targeted protein degradation is widening the scope of druggable proteins against which existing approaches have been ineffective. Examples of targeted protein degraders include molecular glues and proteolysis targeting chimeras (PROTACs): heterobifunctional molecules that bind to proteins of interest and cause proximity‐induced ubiquitination and proteasomal degradation via a linked E3 ligase. Twenty years since their inception, PROTACs have begun progressing through clinical trials, with early success in targeting the oestrogen receptor and androgen receptor in breast and prostate cancer respectively. This review explores important developments in targeted protein degradation to both treat and study cancer. It also considers the potential advantages and challenges in the translational aspects of developing new treatments. © 2024 The Author(s). The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland. [ABSTRACT FROM AUTHOR]

Abstract Introduction Variants of uncertain significance (VUS) are commonly reported in cancer with the widespread adoption of diagnostic massive parallel sequencing. The rate of reclassification of VUS in patients with haematological malignancy is not known and we evaluated this retrospectively. We also investigated whether re‐evaluating VUS in 12–24 months or greater than 24 months post‐initial classification was significant. Method A retrospective audit of patients with haematological malignancies referred to the Molecular Medicine Department at the John Hunter Hospital in Newcastle, Australia between September 2018 and December 2021. Data was analysed for VUS, which was then re‐analysed in standard software using current somatic variant guidelines. Proportions of VUS at baseline were compared to post‐re‐analysis. Results The most common diagnoses in the patient cohort (n = 944) were acute myelogenous leukaemia (41%), myelodysplastic syndrome (31%), and chronic myelomonocytic leukaemia (7%). A total of 210 VUS were re‐analysed. The most common VUS were in the TET2 (20%), RUNX1 (10%) and DNMT3A (9%) genes. A total of 103 were re‐analysed at 24–39 months post‐initial classification and 107 variants were re‐analysed between 12 and 24 months post‐initial classification. Of these, 33 (16%) of VUS were re‐classified at 24–39 months and 12 (11%) were re‐classified at 12–24 months post‐initial classification. The most common variants that were re‐classified in both groups were CSF3R (32%), TET2 (29%), ASXL1 (11%) and ZRSR2 (11%). Conclusion This study on reclassification of VUS in blood cancers demonstrated that one in seven VUS were re‐classified 12 months post initial classification. This can inform practice guidelines and potentially impact the prognosis, diagnosis and treatment of haematological malignancies.

A chemoport is widely used in paediatric oncology population. Removal is a relatively easy procedure, but difficulty can be encountered in case the catheter is densely adherent to the vascular wall. It is a rare complication and is associated with long indwelling duration and acute lymphoblastic leukaemia (ALL). Forceful traction can lead to vascular injury and high morbidity. Herein, we report a 7-year-old girl with precursor B ALL who had delayed chemoport removal due to the coronavirus disease (COVID-19) pandemic. The removal process was difficult, as the catheter was adherent to the right innominate vein. Out of panic, the surgeon pulled it out forcefully. Fortunately, the catheter and its fragment were successfully retrieved completely and the child was discharged the next day. The management strategy varies and ranges from minimally invasive to open surgery. Leaving a stuck chemoport catheter in situ can be a bailout method or part of conservative management.

ABSTRACTPost-transcriptional regulation by RNA binding proteins can determine gene expression levels and drive changes in cancer cell proteomes. Identifying mechanisms of protein-RNA binding, including preferred sequence motifs bound in vivo, provides insights into protein-RNA networks and how they impact mRNA structure, function, and stability. In this review, we will focus on proteins that bind to AU-rich elements (AREs) in nascent or mature mRNA where they play roles in response to stresses encountered by cancer cells. ARE-binding proteins (ARE-BPs) specifically impact alternative splicing, stability, decay and translation, and formation of RNA-rich biomolecular condensates like cytoplasmic stress granules (SGs). For example, recent findings highlight the role of ARE-BPs – like TIAR and HUR – in chemotherapy resistance and in translational regulation of mRNAs encoding pro-inflammatory cytokines. We will discuss emerging evidence that different modes of ARE-BP activity impact leukaemia and lymphoma development, progression, adaptation to microenvironment and chemotherapy resistance.

Background: The review of childhood cancers has most times been done in retrospect by most authors and this has its inherent limitations. Most reviews in Africa show that lymphomas are the commonest malignancies of childhood while acute leukemia ranks much lower. Objective: To do a prospective audit of the pattern of childhood malignancies in Enugu, southeast, Nigeria. Methods: Demographic and medical information on patients aged 1 -17 years admitted over a 36 month period for malignancies was obtained and recorded in pretested interviewed administered questionnaire. Data was analyzed using spss, 15 (Chicago II, USA) software. Results: A total of 103 patients were admitted with diagnosis of cancer with a male: female ratio of 1.3: 1 and median age of 7 years. Majority (63.1%) of patients were from the rural area with low socioeconomic background. There was a decline in the incidence of childhood lymphoma from 40% about 25 years ago to 34% in the present study. Although lymphoma remains the leading childhood malignancy, sarcomas and acute leukemia rather than renal and eye tumors ranked second and third respectively among childhood cancers in the center. Conclusion: There is a reversing trend in the pattern of malignancies of childhood in Enugu as acute leukemia becomes one of the leading malignancies of children.

Abstract Tuberculosis (TB) is a global health threat, especially in HIV patients who may experience immune reconstitution inflammatory syndrome (IRIS) upon Mycobacterium tuberculosis infection. Diagnosing and defining IRIS in non‐HIV patients remains challenging. A 63‐year‐old male with acute leukaemia underwent induction therapy with a regimen containing fludarabine. Febrile neutropenia led to further investigations, revealing non‐cavitary pulmonary TB, prompting anti‐tuberculosis therapy (ATT) alongside resumed leukaemia treatment with sorafenib. Persistent extra‐pulmonary TB, specifically lymph node involvement, were observed and IRIS was suspected, evidenced by enlarged lymphadenopathies, scrofula, and skin lesions that developed during the 13‐month course of ATT, with no recurrence after its cessation. This article explores a case of lymph node TB‐associated paradoxical IRIS in a non‐HIV leukaemia patient, revealing the intricate interplay between tuberculosis and haematological malignancies and emphasizing the lack of standardized diagnostic criteria and treatment consensus. Challenges in lymph node TB diagnosis and management highlight the need for tailored therapeutic approaches. The report explores the potential immunomodulatory effects of fludarabine and sorafenib, questioning their roles in TB‐IRIS. This case illuminates TB‐IRIS dynamics in non‐HIV patients, urging further research and collaborative efforts to enhance understanding and outcomes. As medical complexities persist, personalized therapeutic approaches and advancements in TB‐IRIS research are crucial.

Aim: We present a case of Ecthyma gangrenosum (EG) affecting left thigh in a child with acute lymphoblastic leukaemia (ALL) with an aim to raise awareness about this condition. Case presentation: A 7-year-old female child who presented with lethargy, pallor and lumps to inner lip was diagnosed with B-cell precursor ALL. She was started on treatment as per UKALL 2011 guidelines Regime B. On day 28, she developed neutropenic sepsis along with a new lesion in her left thigh. She was started on intravenous Meropenum, Gentamicin and Caspofungin. The clinical diagnosis of EG was made based on lesion progression, positive blood and wound swab & tissue cultures for Pseudomonas aeruginosa and patient's immunocompromised status. The wound healed with secondary intention following debridement. We present a series of photographs to demonstrate her remarkable improvement. Discussion: EG occurs in 1–30% of cases of Pseudomonas sepsis; other bacteria and fungi can be associated with this condition. It is identified more in oncology patients as seen in our patient. A multidisciplinary team approach should be provided in 3 stages with empirical antibiotics, followed by targeted antibiotics or antifungals & surgical debridement. Our patient was treated in similar fashion and made a good recovery. Conclusion: It is a rare skin condition associated with a high mortality. We suggest all clinicians to be vigilant about this condition to be able to provide accurate diagnosis and prompt treatment to improve the overall prognosis.

Many tumours are organised in a hierarchical structure with at its apex a cell that can maintain, establish, and repopulate the tumour—the cancer stem cell. The haematopoietic stem cell (HSC) is the founder cell for all functional blood cells. Like HSCs, the leukaemia stem cells (LSC) are hypothesised to be the leukaemia‐initiating cells, which have features of stemness such as self‐renewal, quiescence, and resistance to cytotoxic drugs. Immunophenotypically, CD34+CD38− defines HSCs by adding lineage negativity and CD90+CD45RA−. At which stage of maturation the further differentiation is blocked, determines the type of leukaemia, and determines the immunophenotype of the LSC specific to the leukaemia type. No apparent LSC phenotype has been described in lymphoid leukaemia, and it is debated if a specific acute lymphocytic leukaemia‐initiating cell is present, as all cells are capable of engraftment in a secondary mouse model. In chronic lymphocytic leukaemia, a B‐cell clone is responsible for uncontrolled proliferation, not a specific LSC. In chronic and acute myeloid leukaemia, LSC is described as CD34+CD38− with the expression of a marker that is aberrantly expressed (LSC marker), such as CD45RA, CD123 or in the case of chronic myeloid leukaemia CD26. In acute myeloid leukaemia, the LSC load had prognostic relevance and might be a biomarker that can be used for monitoring and as an addition to measurable residual disease. However, challenges such as the CD34‐negative immunophenotype need to be explored. [ABSTRACT FROM AUTHOR]

Summary: Methotrexate (MTX), although an indispensable part of contemporary treatment protocols for childhood acute lymphoblastic leukaemia (ALL)/lymphomas (LBL) in improving outcomes, can lead to serious neurotoxicity with long‐term consequences. The aetiopathogenesis, predisposing factors and treatment for MTX‐induced neurotoxicity are not yet well defined. The aim of our study was to detect the incidence, risk factors and to assess the overall outcomes of MTX‐induced neurotoxicity among large cohort of paediatric ALL/LBL patients treated on a uniform protocol. We conducted retrospective audit of medical records of 622 consecutive children (≤14 years) diagnosed with ALL and LBL between January 2018 and December 2022 and treated on modified BFM‐95 protocol at the Department of Pediatric Oncology, Regional Cancer Centre, Thiruvananthapuram. Risk factors predisposing to MTX‐induced neurotoxicity were identified using binary logistic regression analysis. Forty‐three children were diagnosed with MTX‐induced neurotoxicity with an incidence rate of 6.9%. More than two‐thirds of them had high‐grade MTX‐induced neurotoxicity CTCAE v5.0 with a median age of 9 years (range: 9 months to 14 years). Almost half of them developed MTX neurotoxicity during Protocol M followed by Phase‐Ib consolidation (15%). Majority of these patients (84%, 36/43) were challenged again with MTX, with 11% (4/36) developing recurrence. Fifteen per cent had persistent neurological deficits at last follow‐up. Univariate analysis found older age (age > 5 years) (p < 0.001), T‐cell phenotype (p = 0.040), tumour lysis syndrome during induction (p < 0.001), baseline renal problems prior to MTX exposure (p < 0.001) and CNS leukaemic involvement (p < 0.003) to be significantly associated with MTX neurotoxicity. On multivariate analysis, older age (>5 years), tumour lysis during induction and CNS leukaemia retained statistical significance (p < 0.05). Methotrexate‐induced neurotoxicity during paediatric acute lymphoblastic leukaemia/lymphoma therapy is a transient phenomenon in majority and re‐challenge with MTX is generally safe. Older age children who develop tumour lysis during induction and CNS leukaemic involvement are at increased risk for MTX‐induced neurotoxicity during ALL/LBL treatment. [ABSTRACT FROM AUTHOR]

The present study analyses the clinical characteristics of patients diagnosed with cutaneous fusarium through a systematic review of cases reported in literature. A total of 39 cases were included, of which 53% were men, 30% were women, and in 17% the sex was not specified. The age ranged from 5 to 85 years. Most cases were reported in Brazil, followed by Japan and United States of America. The most common agent was Fusarium solani, in 37.5% of the patients. Most of the affected individuals had acute myeloid leukaemia and some of the predisposing factors, which included induction chemotherapy, febrile neutropenia, and bone marrow transplantation. The clinical topography of the lesions was located in 27.5% and disseminated in 72.5%, with the most observed clinical feature outstanding the presence of papules and nodules with central necrosis in 47% of the cases. Longer survival was demonstrated in those treated with more than three antifungals. It is concluded that cutaneous fusarium is a complex and challenging clinical entity, infection in patients with leukaemias underscores the need for thorough care to decrease morbidity and mortality. [ABSTRACT FROM AUTHOR]

Leukaemia image classification involves using machine learning, and often deep learning, techniques to automatically analyse medical images and categorize them into different classes, such as different types of leukaemia or distinguishing between leukaemia and normal cells. Leukaemia, a kind of cancer that may occur in individuals of all ages, including kids and adults, is a significant contributor to worldwide death rates. Additionally, inspection under a microscope, leukemic cells look and develop similarly to normal cells, making identification more difficult. Traditional machine learning models may struggle to scale effectively with the increasing size and complexity of medical image datasets. As the datasets grow, the limitations of manually engineered features and shallow architectures become more apparent. In the context of leukaemia image classification using deep learning, the primary aim is to develop a robust and accurate model that can effectively distinguish between different types of leukaemia or between leukaemia and normal cells within medical images. As a consequence, the study provided a unique deep learning approach known as optimized deep recurrent neural network (ODRNN) for identifying leukaemia sickness by analysing microscopic images of blood samples. Deep recurrent neural networks (DRNNs) are used in the recommended strategy for diagnosing leukaemia, and then, the red deer optimization algorithm (RDOA) applies to optimize the weight gained by DRNN. The weight of DRNN from RDOA will be tuned on the deer roaring rate behaviour. The model that has been proposed is evaluated on two openly accessible leukaemia blood sample datasets, AML, ALL_IDB1, and ALL_IDB2. The research work uses statistical metrics related to disease including specificity, recall, accuracy, precision, and F1-score to assess the effectiveness of the proposed model for identification and classification. The proposed method achieves highly impressive results, with scores of 98.96%, 99.85%, 99.98%, 99.23%, and 99.98%, respectively. In conclusion, deep learning-based image classification for leukaemia has emerged as a powerful and promising approach in the field of medical diagnostics. Leveraging ODRNN, researchers and practitioners have made significant strides in automating the process of identifying and classifying leukaemia cells in medical images. [ABSTRACT FROM AUTHOR]

This study discusses the importance of minimal residual disease (MRD) detection in acute myeloid leukemia (AML) patients using liquid biopsy and next-generation sequencing (NGS). AML prognosis is based on various factors, including genetic alterations. NGS has revealed the molecular complexity of AML and helped refine risk stratification and personalized therapies. The long-term survival rates for AML patients are low, and MRD assessment is crucial in predicting prognosis. Currently, the most common methods for MRD detection are flow cytometry and quantitative PCR, but NGS is being incorporated into clinical practice due to its ability to detect genomic aberrations in the majority of AML patients. Typically, bone marrow samples are used for MRD assessment, but using peripheral blood samples or liquid biopsies would be less invasive. Leukemia originates in the bone marrow, along with the cfDNA obtained from peripheral blood. This study aimed to assess the utility of cell-free DNA (cfDNA) from peripheral blood samples for MRD detection in AML patients. A cohort of 20 AML patients was analyzed using NGS, and a correlation between MRD assessment by cfDNA and circulating tumor cells (CTCs) in paired samples was observed. Furthermore, a higher tumor signal was detected in cfDNA compared to CTCs, indicating greater sensitivity. Challenges for the application of liquid biopsy in MRD assessment were discussed, including the selection of appropriate markers and the sensitivity of certain markers. This study emphasizes the potential of liquid biopsy using cfDNA for MRD detection in AML patients and highlights the need for further research in this area. [ABSTRACT FROM AUTHOR]

Leukemia is a life-threatening malignant tumor of the hematopoietic system. Currently, the main treatment modalities are chemotherapy and hematopoietic stem cell transplantation. However, increased drug resistance due to decreased sensitivity of leukemia cells to chemotherapeutic drugs presents a major challenge in current treatments. Autophagy-associated proteins involved in autophagy initiation have now been shown to be involved in the development of various types of leukemia cells and are associated with drug resistance. Therefore, this review will explore the roles of autophagy-related proteins involved in four key autophagic processes: induction of autophagy and phagophore formation, phagophore extension, and autophagosome formation, on the development of various types of leukemias as well as drug resistance. Autophagy may become a promising therapeutic target for treating leukemia. [ABSTRACT FROM AUTHOR]

Acute lymphoblastic leukaemia is currently treated with bacterial L-asparaginase; however, its side effects raise the need for the development of improved and efficient novel enzymes. Previously, we obtained low anti-asparaginase antibody production and high serum enzyme half-life in mice treated with the P40S/S206C mutant; however, its specific activity was significantly reduced. Thus, our aim was to test single mutants, S206C and P40S, through in vitro and in vivo assays. Our results showed that the drop in specific activity was caused by P40S substitution. In addition, our single mutants were highly stable in biological environment simulation, unlike the double-mutant P40S/S206C. The in vitro cell viability assay demonstrated that mutant enzymes have a higher cytotoxic effect than WT on T-cell-derived ALL and on some solid cancer cell lines. The in vivo assays were performed in mice to identify toxicological effects, to evoke immunological responses and to study the enzymes' pharmacokinetics. From these tests, none of the enzymes was toxic; however, S206C elicited lower physiological changes and immune/allergenic responses. In relation to the pharmacokinetic profile, S206C exhibited twofold higher activity than WT and P40S two hours after injection. In conclusion, we present bioengineered E. coli asparaginases with high specific enzyme activity and fewer side effects. [ABSTRACT FROM AUTHOR]

In acute lymphoblastic leukaemia (ALL), elevated foetal haemoglobin (HbF) levels have been associated with the prognosis of patients. Genetic variants in HbF regulatory genes: BAF chromatin remodelling complex subunit (BCL11A), HBS1L-MYB transcriptional GTPase intergenic region (HBS1L-MYB), Krüppel-like factor 1 (KLF1), haemoglobin gamma subunit 2 (HBG2), haemoglobin gamma subunit 1 (HBG1), and haemoglobin subunit beta pseudogene 1 (HBBP1) are often associated with elevated HbF concentration. This study investigated the association of genetic variants in HbF regulatory genes with HbF concentration, unfavourable prognosis, and outcome in children with ALL. We quantified HbF concentration and genotyped 17 genetic variants in 48 patients with ALL and 64 children without ALL as a reference group. HbF concentration was higher in patients than in the reference group (4.4% vs 1.4%), and 75% (n = 36) of the patients had HbF > 2.5%. Unfavourable prognosis ALL was established in 68.8% (n = 33) of the patients. Variant HBG2 rs7482144 was associated with high HbF concentration (P = 0.015); while HBS1L-MYB rs9399137 (P = 0.001), HBG2 rs7482144 (P = 0.001) and the β-globin genes HBG2, HBG1, and HBPP1 haplotype TGC (P = 0.017) with unfavourable prognosis ALL. Additionally, variant BCL11A rs4671393 showed a protective role (P = 0.0001). In conclusion, variants HBG2 rs7482144, HBS1L-MYB rs9399137 and BCL11A rs4671393 may play a significant role in ALL. [ABSTRACT FROM AUTHOR]

Invasive aspergillosis is associated with significant morbidity and mortality in patients with haematologic malignancies and haematopoietic cell transplant recipients. The prognosis is worse among patients who have failed primary antifungal treatment. We aim to provide guidance on the diagnosis and management of refractory invasive pulmonary aspergillosis. Using PubMed, we performed a review of original articles, meta-analyses, and systematic reviews. We discuss the diagnostic criteria for invasive pulmonary aspergillosis and the evidence on the treatment of primary infection. We outline our diagnostic approach to refractory disease. We propose a treatment algorithm for refractory disease and discuss the role of experimental antifungal agents. For patients with worsening disease while on antifungal therapy, a thorough diagnostic evaluation is required to confirm the diagnosis of aspergillosis and exclude another concomitant infection. Treatment should be individualized. Current options include switching to another triazole, transitioning to a lipid formulation of amphotericin B, or using combination antifungal therapy. [ABSTRACT FROM AUTHOR]

Aims: The aim was to analyse the use and safety of bisphosphonate treatment for metabolic bone complications in paediatric cancer patients. Methods: We retrospectively describe our experience with bisphosphonate treatment in 25 childhood cancer patients (aged <18 years) in a single tertiary hospital between 1999 and 2020. Results: The most common primary diagnosis was acute lymphoblastic leukaemia (n = 16) and Hodgkin lymphoma (n = 3). Eleven patients (44%) had received allogeneic stem cell transplantation and two patients autologous stem cell transplantation. Sixteen patients (64%) had been treated with radiotherapy, either total-body (n = 11) or local (n = 5). The main indication for bisphosphonates was osteoporosis with vertebral compression fractures in 13/25, osteonecrosis in 6/25 and hypercalcaemia in 2/25. The bisphosphonate treatment was started on average 13 (range 0-76) months after the diagnosis of the bone complication. Bisphosphonate treatment lasted between weeks (hypercalcaemia) to 5 years (severe osteoporosis). Mild, non-symptomatic hypophosphatemia (n = 8), hypocalcaemia (n = 6) and moderate, transient pain (n = 6) were the most common adverse effects. No severe side effects were observed even when bisphosphonates were administered concomitantly with chemotherapy. Bone mineral density significantly improved with the bisphosphonate treatment (mean lumbar spine Z-score -1.17 vs. -0.07, p < 0.001). Conclusion: Bisphosphonate treatment was well tolerated in this paediatric patient cohort. [ABSTRACT FROM AUTHOR]

Summary: Pocket motifs and their amino acid positions of HLA molecules are known to govern antigen presentation to effector cells. Our objective was to analyse their influence on the risk of graft‐versus‐host disease (GVHD) and relapse after umbilical cord blood transplant (UCBT). The transplant characteristics of 849 patients with acute leukaemia were obtained from the Eurocord/EBMT database. Higher acute (a) GVHD was associated with homozygosity of UCB HLA‐C amino acid positions 77 and 80 (NN/KK) (p = 0.008). Severe aGVHD was associated with HLA‐A pocket B YSAVMENVHY motif (p = 0.002) and NN and RR genotypes of the HLA‐C amino acid positions 77 and 156 (p = 0.006 and p = 0.002). Such risk was also increased in case of recipient and UCB mismatches in P4 (p < 0.0001) and P9 (p = 0.003) pockets of HLA‐DQB1 alleles. For chronic GVHD, the pocket B YYAVMEISNY motif of the HLA‐B*15:01 allele and the absence of mismatch between recipient and UCB in the P6 pocket of HLA‐DRB1 were associated with a lower risk (p = 0.0007 and p = 0.0004). In relapse, both UCB pocket B YFAVMENVHY belonging to HLA‐A*32:01 and recipient pocket B YDSVGENYQY motif of the HLA‐C*07:01 allele were associated with higher risk (p = 0.0026 and p = 0.015). We provide clues on HLA‐mediated cellular interactions and their role in the development of GVHD and relapse. [ABSTRACT FROM AUTHOR]

This study aimed to conduct a thorough analysis of peripheral blood smear findings in acute and chronic leukaemia's at a tertiary care centre, utilizing the 5th edition of the WHO classification (2022) for diagnosis and employing cytochemical staining to differentiate between Acute Myeloid Leukaemia (AML) and Acute Lymphoblastic Leukaemia (ALL). Methods: A retrospective analysis was performed on peripheral blood smear findings of 300 cases, including 30 cases of acute leukaemia, at a tertiary care centre. Diagnosis was based on standardized diagnostic criteria, and cytochemical staining was utilized for subtype differentiation. Data on patient demographics, leukaemia subtype, and peripheral blood smear characteristics were collected and analysed. Results: Among the 30 acute leukaemia cases, CML constituted 16 cases, while 12 cases were identified as AML and 2 cases as ALL. Peripheral blood smear analysis revealed distinct morphological features corresponding to each leukaemia subtype. Cytochemical staining aided in confirming the lineage differentiation between AML and ALL. Conclusion: Peripheral blood smear analysis, guided by standardized diagnostic criteria and complemented by ancillary tests such as cytochemical staining, plays a crucial role in leukaemia diagnosis and classification. Continued research and collaboration are essential for advancing diagnostic algorithms and improving patient care in the management of leukaemia's. [ABSTRACT FROM AUTHOR]

The objective of this work is to create a diagnostic tool for the early diagnosis of leukaemia which is a serious type of cancer affecting bones and blood. Acute lymphoblastic leukemia (ALL) is the most dangerous form of leukemia. Doctors diagnose it by blood samples under powerful microscopes with enhanced lenses which can be slow and is sometimes affected by disagreements among experts. Therefore, the purpose of this work was to create a profound diagnostic tool for the early diagnosis of leukaemia. We proposes an Optimized Light Weight CNN to detect ALL at the early stage. Fragmentation and classification based on preprocessing are the two main components of the suggested method. Artificial images are created during the segmentation process and then tamed by chromatic modification. The proposed model is used to extract the best deep features from every blood smear image to predict the presence of ALL. The work was tested by two lymphoblastic leukaemia image databases (ALL_IDB1 and ALL_ IDB2). Deep-learning (DL) models-based segmentation and classification techniques have recently been introduced for detecting ALL; however they still have certain drawbacks. The proposed approach was assessed with few DL parameters like accuracy, F1 score, precision, recall and Area under the curve. In comparison to the most recent research studies already published; the suggested strategy produced exceptional classification accuracy as 99.56%, F1 score as 99.53%. [ABSTRACT FROM AUTHOR]

The main objective of this study was to investigate the production and activity of glutaminase by some clinical bacterial species. Two marine specimens, saltwater and sediment gathered from the Red Sea coast of Hurghada, Egypt, yielded 100 marine bacterial isolates altogether. Based on cultural and biochemical testes, there were 60 isolates of Gram-negative bacteria belong to the Escherichia coli, including 10, isolates of Pseudomonas aeruginosa, 25 isolates of Klebsiella pneumoniae (K. pneumonia) and 2 Acinetobacter junii. Whereas the remaining isolates were identified as Gram-positive bacteria were distributed as 3 Enterococcus faecalis. All the bacterial isolates were screened for L-glutaminase enzyme activity using rapid plate assay. The isolate showing the highest production of L-glutaminase was identified by 16S rDNA gene sequence analysis. Then L-glutaminase production was optimized by various process parameters such as: The effect of incorporation of additional carbon source, nitrogen source, different concentrations of sodium chloride (0.2-1.2 %), initial pH values (4-9), incubation temperatures (25-50°C), and incubation periods (24-120 h.). Fifty isolates were found to be L-glutaminase producers. The zone index was calculated for all L-glutaminase producing samples which are ranged from 5.0 to 1.0. The maximum zone index was given by K. pneumonia. The enzymatic activity was ranged from (82.75±4.71-15.7±0.86) IU/ml. The maximum activity was recorded by K. pneumonia. Various parameters that enhance the yield of L-glutaminase by K. pneumonia was investigated and resulted in fructose was the best carbon source, beef extract was the best nitrogen source, 1% of NaCl concentration was the optimum for L-glutaminase production from K. pneumonia, the optimum L-glutaminase production was recorded at pH 8.0, The maximum enzyme productivity was obtained at 96 h., Maximum L-glutaminase production was noticed at a temperature of 40°C. In conclusion, the current study showed microbial source of glutaminase enzyme production from K. pneumonia pure culture. Nutritional parameters, such as carbon and nitrogen sources also played an important role in enhancing the yield. [ABSTRACT FROM AUTHOR]

Abstract This study aimed to investigate the impact of Vernonia amygdalina leaf extract on FLT3 regulation. V. amygdalina was extracted with 96% ethanol (VAE-96), and its cytotoxicity against FLT3- cell lines (MOLM-13 and MV-4-11) was evaluated. The results indicated that VAE-96 induced apoptosis in these cells and inhibited the phosphorylation of AKT, MAPK, and FLT3. Additionally, VAE-96 substantially diminished the activity of the FLT3 promoter and the expression of FLT3 mRNA. The extract was found to contain alkaloids, saponin, reduced sugar compounds, and polyphenols, including tannins and flavonoids, as per the phytoconstituents analysis. The potential of alkaloid fractions on MOLM-13 cells was indicated by the robust cytotoxic effect of the alkaloid fractions, which resulted in over 50% cell mortality at 30 µg/ml. Our results suggest that VAE-96 may be a beneficial agent for the prevention and treatment of AML with FLT3-ITD mutation.

Summary: Background: Autoimmune diseases are known to be associated with an increased risk of cancer. Whether maternal immune dysregulation can have an impact on the development of haematological malignancies in offspring remains uncertain. Therefore, we explored the association between offspring risk of haematological malignancies and maternal autoimmune disease using a real-world nationwide population-based study. Methods: In this case–control study, we identified 2172 children with haematological malignancies between 2004 and 2019 from Taiwan's National Health Insurance program and compared them with population-based controls without haematologic malignancies, who were matched with each individual at a ratio of 1:4. The medical information of the autoimmune mothers were obtained from the Taiwan Maternal and Child Health Database. Conditional logistic regression was used to estimate the odds ratio for haematologic malignancy in offspring. Furthermore, subgroup and stratified analyses were conducted. Findings: Among the rheumatologic diseases in our study, Crohn's disease was the most common disease both in the haematological malignancy group (1.1%) and the control group (0.9%). In multivariable analysis, the odds ratio for haematological malignancy in offspring with maternal autoimmune diseases was 1.2 (95% confidence interval [CI] 0.91–1.58). The overall risk of haematologic malignancy was not significantly higher when adjusted for specific risk factors, including neonatal age, maternal age, family income, urbanization, maternal occupation, birth weight, or maternal comorbidity, except for prematurity. When comparing different autoimmune diseases among haematological malignancies and the control group, maternal psoriatic arthritis/psoriasis had the highest adjusted overall risk for haematological malignancies (adjusted OR 2.11, CI 0.89–5), followed by ankylosing spondylitis (adjusted OR 1.45, CI 0.7–3), autoimmune thyroiditis (OR 1.26, CI 0.57–2.81), systemic lupus erythematosus (OR 1.21, CI 0.48–3.02), Crohn's disease (OR 1.19, CI 0.75–1.9), and Sjogren's syndrome (OR 1.18, CI 0.65–2.15), but no significance was reached in these analyses. Multivariable analysis of risk factors associated with haematological malignancy subtypes was done. It showed no associations between maternal autoimmune disease and childhood haematological malignancies. Interpretation: We found no significant relationship between maternal autoimmune disease and childhood haematological malignancies. The influence of maternal immune dysregulation on the next generation with respect to haematological malignancies development may be limited. Funding: There was no funding source for this study.

Introduction: The spectrum of haematological and non haematological disorders is vast in various age groups. Complete blood counts and other routine laboratory tests are not always sufficient to diagnose these diseases. Bone marrow examination plays an important role in diagnosing their underlying causes. Aim: To analyse the spectrum of various haematological and non haematological disorders reported in Bone Marrow Aspiration (BMA) and compare them with Bone Marrow Trephine Biopsy (BMB) and Flow Cytometry (FCM) findings where applicable. Materials and Methods: A one-year cross-sectional study was conducted in the Department of Clinical Pathology, PGIMS, Rohtak, Haryana, India from April 2022 to March 2023. A total of 518 consecutive BMA samples were morphologically analysed. Comparative evaluations were performed among BMA, BMB, and FCM where applicable. Diagnostic accuracy was calculated, and the findings of discordant cases were tabulated. Definitive diagnosis of lymphoma/leukaemia and Paroxysmal Nocturnal Haemoglobinuria (PNH) cases were made using FCM. Results: The patients’ ages ranged from three months to 86 years, with a mean age of 38.4 years. The male to female ratio was 1.3:1, with a slight male predominance. The highest number of cases were of anaemia {183 (35.3%) and 164 (31.7%), respectively} and leukaemia {128 (24.7%) and 134 (25.9%), respectively}, followed by normal marrow studies {39 (7.5%) and 32 (6.2%), respectively} and megakaryocytic thrombocytopenia {24 (4.6% in each} in both BMA and biopsy. Among anaemia cases {183 and 164 cases in BMA and BMB}, the majority were of the megaloblastic type {62 (33.8%) and 54 (32.9%), respectively}, followed by hypoplastic/aplastic type {40 (21.8%) and 50 (30.5%), respectively}. In cases of leukaemia (128 and 134 cases in BMA and BMB), acute leukaemia cases (76 (59.4%) and 82 (61.2%), respectively} outnumbered chronic leukaemia cases {52 (40.6%) and 52 (38.8%), respectively} in both BMA and BMB. The concordance and discordance rate between BMA and BMB were 87.6% (419 cases) and 12.4% (59 cases), respectively. Diagnosis was exclusively made by BMB in cases of myelofibrosis, granulomatous disease, and Hodgkin’s lymphoma. Conclusion: BMA cytology is a relatively safe and mildly invasive technique for evaluating various haematological and non haematological disorders with better preservation of cellular morphology. However, in cases with dry/blood taps and focal marrow involvement, BMB should be performed, as it shows well-preserved marrow architecture with all its cellular and stromal components. FCM is a definitive diagnostic modality for further categorisation of acute leukaemia and Chronic Lymphoproliferative Disorders (CLPD).

Abstract Background Increased malignancy frequency is well documented in adult-systemic lupus erythematosus (SLE), but with limited reports in childhood-onset SLE (cSLE) series. We explored the frequency of malignancy associated with cSLE, describing clinical and demographic characteristics, disease activity and cumulative damage, by the time of malignancy diagnosis. Method A retrospective case-notes review, in a nationwide cohort from 27 Pediatric Rheumatology centres, with descriptive biopsy-proven malignancy, disease activity/damage accrual, and immunosuppressive treatment were compiled in each participating centre, using a standard protocol. Results Of the 1757 cSLE cases in the updated cohort, 12 (0.7%) developed malignancy with median time 10 years after cSLE diagnosis. There were 91% females, median age at cSLE diagnosis 12 years, median age at malignancy diagnosis 23 years. Of all diagnosed malignancies, 11 were single-site, and a single case with concomitant multiple sites; four had haematological (0.22%) and 8 solid malignancy (0.45%). Median (min–max) SLEDAI-2 K scores were 9 (0–38), median (min–max) SLICC/ACR-DI (SDI) score were 1 (1–5) Histopathology defined 1 Hodgkin's lymphoma, 2 non-Hodgkin's lymphoma, 1 acute lymphoblastic leukaemia; 4 gastrointestinal carcinoma, 1 squamous cell carcinoma of the tongue and 1 anal carcinoma; 1 had sigmoid adenocarcinoma and 1 stomach carcinoid; 3 had genital malignancy, being 1 vulvae, 1 cervix and 1 vulvae and cervix carcinomas; 1 had central nervous system oligodendroglioma; and 1 testicle germ cell teratoma. Conclusion Estimated malignancy frequency of 0.7% was reported during cSLE follow up in a multicentric series. Median disease activity and cumulative damage scores, by the time of malignancy diagnoses, were high; considering that reported in adult series.

Xinjun Hou,1 Yanhui Han,2 Abdurahman Hajinur Hirad,3 Abdullah A Alarfaj,3 Linxiang Liu4 1Department of Traditional Chinese Medicine Hematology, Xin’an People’s Hospital, Luoyang, Henan, 471000, People’s Republic of China; 2Department of Internal Medicine of Traditional Chinese Medicine, Xin’an the Second People’s Hospital, Luoyang, Henan, 471000, People’s Republic of China; 3Department of Botany and Microbiology, College of Science, King Saud University, Riyadh, 11451, Saudi Arabia; 4Department of Hematology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, 450052, People’s Republic of ChinaCorrespondence: Linxiang Liu, Department of Hematology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, People’s Republic of China, Email liulx2021@sina.comBackground: The present study aimed to investigate the protective effect of icaritin (ICT) on ENU-induced leukemia in male mice.Methods: The mice received intraperitoneal injections of 80 mg/kg ENU twice a week for three months for induction of leukemia. Blood smears from these mice showed blast cells, confirming the presence of leukemia. After confirming leukemia, mice were divided into control, ENU-induced leukemia, and leukemia groups (10 mg/kg bw and 20 mg/kg bw) were treated with ICT for 35 days. Blood, spleen, and liver samples were collected for analysis. The expression of IL-6, JAK2, STAT3, as well as inflammatory, pro-apoptotic (Bax), and anti-apoptotic (Bcl-2) proteins were evaluated using qPCR, immunohistochemistry, and immunofluorescence techniques.Results: The study found that ICT inhibited inflammation and the IL-6/JAK2/STAT3 pathway in ENU-induced mice. ICT treatment induced apoptosis in the spleen and liver by activating Bax and downregulating Bcl-2. The findings provide novel evidence that ICT acts as a dual inhibitor of IL-6/JAK2/STAT3 signaling, promoting apoptosis and playing an essential role in anti-leukemic activity.Conclusion: These results suggest that ICT has potential as a therapeutic target for treating leukemia, offering a novel approach to leukemia treatment through inhibiting the IL-6/JAK2/STAT3 pathway and induction of apoptosis.Keywords: N-ethyl-n-nitrosourea, leukaemia, ICT, IL-6/JAK2/STAT3, inflammation, apoptosis

T-cell acute lymphoblastic leukaemia (T-ALL) is a bone marrow (BM) malignancy affecting children and adults. Typically treated with chemotherapy, leukaemia remains a major death cause in people under 20 years old. Understanding molecularly altered pathways in T-ALL may lead to new therapeutic avenues in the future. Ras pathway dysregulation is common in T-ALL. We have shown elevated expression levels of the Ras guanine nucleotide exchange factor RasGRP1 in T-ALL patients, which results in constant production of active Ras (RasGTP). When leukaemia cell lines are exposed to cytokines, RasGTP levels further increase in a RasGRP1-dependent manner. How overexpressed RasGRP1 may impact primary BM cells has remained unknown. We recently published a new RoLoRiG mouse model that allows for pIpC-induced overexpression of RasGRP1 in haematopoietic cells, which can be traced with an ires-EGFP cassette. This novel model revealed that RasGRP1 overexpression bestows a fitness advantage to haematopoietic stem cells (HSCs) over wild-type cells. Intriguingly, this increased fitness only manifests in native Hematopoiesis, and not in BM transplantation (BMT) assays. In this commentary, we summarize key features of our RoLoRiG model, elaborate on BM niche importance, and discuss differences between native Hematopoiesis and BMT in the context of stem cell metabolism.

Sufficient evidence supports a relationship between certain myeloid neoplasms and exposure to benzene or formaldehyde. DNA methylation could underlie benzene- and formaldehyde-induced health outcomes, but data in exposed human populations are limited. We conducted two cross-sectional epigenome-wide association studies (EWAS), one in workers exposed to benzene and another in workers exposed to formaldehyde. Using HumanMethylation450 BeadChips, we investigated differences in blood cell DNA methylation among 50 benzene-exposed subjects and 48 controls, and among 31 formaldehyde-exposed subjects and 40 controls. We performed CpG-level and regional-level analyses. In the benzene EWAS, we found genome-wide significant alterations, i.e., FWER-controlled P-values

Summary: Among 301 newly diagnosed patients with acute myeloid leukaemia receiving venetoclax and a hypomethylating agent, 23 (7.6%) experienced major cardiac complications: 15 cardiomyopathy, 5 non‐ST elevation myocardial infarction and/or 7 pericarditis/effusions. Four patients had more than one cardiac complication. Baseline characteristics included median age ± interquartile range; 73 ± 5 years; 87% males; 96% with cardiovascular risk factors; and 90% with preserved baseline ejection fraction. In multivariate analysis, males were more likely (p = 0.02) and DNMT3A‐mutated cases less likely (p < 0.01) to be affected. Treatment‐emergent cardiac events were associated with a trend towards lower composite remission rates (43% vs. 62%; p = 0.09) and shorter survival (median 7.7 vs. 13.2 months; p < 0.01). These observations were retrospectively retrieved and warrant further prospective examination. [ABSTRACT FROM AUTHOR]

Summary: Chronic myelomonocytic leukaemia (CMML) is a rare haematological disorder characterized by monocytosis and dysplastic changes in myeloid cell lineages. Accurate risk stratification is essential for guiding treatment decisions and assessing prognosis. This study aimed to validate the Artificial Intelligence Prognostic Scoring System for Myelodysplastic Syndromes (AIPSS‐MDS) in CMML and to assess its performance compared with traditional scores using data from a Spanish registry (n = 1343) and a Taiwanese hospital (n = 75). In the Spanish cohort, the AIPSS‐MDS accurately predicted overall survival (OS) and leukaemia‐free survival (LFS), outperforming the Revised‐IPSS score. Similarly, in the Taiwanese cohort, the AIPSS‐MDS demonstrated accurate predictions for OS and LFS, showing superiority over the IPSS score and performing better than the CPSS and molecular CPSS scores in differentiating patient outcomes. The consistent performance of the AIPSS‐MDS across both cohorts highlights its generalizability. Its adoption as a valuable tool for personalized treatment decision‐making in CMML enables clinicians to identify high‐risk patients who may benefit from different therapeutic interventions. Future studies should explore the integration of genetic information into the AIPSS‐MDS to further refine risk stratification in CMML and improve patient outcomes. [ABSTRACT FROM AUTHOR]

Aims: The discovery of somatic genetic alterations established many histiocytic disorders as haematologic neoplasms. We aimed to investigate the demographic characteristics and additional haematologic cancers of patients diagnosed with histiocytic disorders in The Netherlands. Methods and results: We retrieved data on histiocytosis patients from the Dutch Nationwide Pathology Databank (Palga). During 1993 to 2022, more than 4000 patients with a pathologist‐assigned diagnosis of a histiocytic disorder were registered in Palga. Xanthogranulomas were the most common subtype, challenging the prevailing assumption that Langerhans cell histiocytosis (LCH) is the most common histiocytic disorder. LCH and juvenile xanthogranuloma (JXG) had a peak incidence in the first years of life; males were overrepresented among all histiocytosis subgroups. 118 patients had a histiocytic disorder and an additional haematologic malignancy, including 107 (91%) adults at the time of histiocytosis diagnosis. In 16/118 patients, both entities had been analysed for the same genetic alteration(s). In 11 of these 16 patients, identical genetic alterations had been detected in both haematologic neoplasms. This included two patients with PAX5 p.P80R mutated B cell acute lymphoblastic leukaemia and secondary histiocytic sarcoma, further supporting that PAX5 alterations may predispose (precursor) B cells to differentiate into the myeloid lineage. All 4/11 patients with myeloid neoplasms as their additional haematologic malignancy had shared N/KRAS mutations. Conclusions: This population‐based study highlights the frequency of xanthogranulomas. Furthermore, our data add to the growing evidence supporting clonal relationships between histiocytic/dendritic cell neoplasms and additional myeloid or lymphoid malignancies. Particularly adult histiocytosis patients should be carefully evaluated for the development of these associated haematologic cancers. [ABSTRACT FROM AUTHOR]

Introduction: The spectrum of haematological and non haematological disorders is vast in various age groups. Complete blood counts and other routine laboratory tests are not always sufficient to diagnose these diseases. Bone marrow examination plays an important role in diagnosing their underlying causes. Aim: To analyse the spectrum of various haematological and non haematological disorders reported in Bone Marrow Aspiration (BMA) and compare them with Bone Marrow Trephine Biopsy (BMB) and Flow Cytometry (FCM) findings where applicable. Materials and Methods: A one-year cross-sectional study was conducted in the Department of Clinical Pathology, PGIMS, Rohtak, Haryana, India from April 2022 to March 2023. A total of 518 consecutive BMA samples were morphologically analysed. Comparative evaluations were performed among BMA, BMB, and FCM where applicable. Diagnostic accuracy was calculated, and the findings of discordant cases were tabulated. Definitive diagnosis of lymphoma/leukaemia and Paroxysmal Nocturnal Haemoglobinuria (PNH) cases were made using FCM. Results: The patients' ages ranged from three months to 86 years, with a mean age of 38.4 years. The male to female ratio was 1.3:1, with a slight male predominance. The highest number of cases were of anaemia {183 (35.3%) and 164 (31.7%), respectively} and leukaemia {128 (24.7%) and 134 (25.9%), respectively}, followed by normal marrow studies {39 (7.5%) and 32 (6.2%), respectively} and megakaryocytic thrombocytopenia {24 (4.6% in each} in both BMA and biopsy. Among anaemia cases {183 and 164 cases in BMA and BMB}, the majority were of the megaloblastic type {62 (33.8%) and 54 (32.9%), respectively}, followed by hypoplastic/aplastic type {40 (21.8%) and 50 (30.5%), respectively}. In cases of leukaemia (128 and 134 cases in BMA and BMB), acute leukaemia cases (76 (59.4%) and 82 (61.2%), respectively} outnumbered chronic leukaemia cases {52 (40.6%) and 52 (38.8%), respectively} in both BMA and BMB. The concordance and discordance rate between BMA and BMB were 87.6% (419 cases) and 12.4% (59 cases), respectively. Diagnosis was exclusively made by BMB in cases of myelofibrosis, granulomatous disease, and Hodgkin's lymphoma. Conclusion: BMA cytology is a relatively safe and mildly invasive technique for evaluating various haematological and non haematological disorders with better preservation of cellular morphology. However, in cases with dry/blood taps and focal marrow involvement, BMB should be performed, as it shows well-preserved marrow architecture with all its cellular and stromal components. FCM is a definitive diagnostic modality for further categorisation of acute leukaemia and Chronic Lymphoproliferative Disorders (CLPD). [ABSTRACT FROM AUTHOR]

Objectives: This study examines the associations of active matrix metalloproteinase‐8 (aMMP‐8) point‐of‐care immunotest (Periosafe) outcomes with oral health of patients with haemato‐oncologic diseases. Methods: Adult patients diagnosed with haematological diseases aimed to be treated with haematopoietic stem cell transplantation (HSCT) between 2018 and 2019 were included in the study. Clinical and radiological dental examination were taken immediately prior to transplantation. The presence of oral foci of infections, caries or periodontitis was examined and compared with the outcomes of aMMP‐8 immunotest. Results: Acute oral infection foci were present in 11.9%, chronic in 44.1% and periodontitis in 42.0% of the 143 subjects. aMMP‐8 immunotest was positive in 13.3% of all the 143 subjects. Among subjects with periodontitis (n = 60), the aMMP‐8 immunotest was also positive in 13.3% of these subjects. However, the subjects with positive aMMP‐8 immunotest (n = 19) had more often acute or chronic infection foci and more than one of the examined dental treatment needs compared with subjects with negative immunotest (all p < 0.05). There were no differences in age, sex, hyposalivation, DMFT‐index values nor with plasma levels of leukocytes, neutrophils or C‐reactive protein between subjects with positive or negative aMMP‐8 immunotest. Conclusions: aMMP‐8 immunotest accuracy might be reduced, in relation to periodontitis, in haemato‐oncologic patients. [ABSTRACT FROM AUTHOR]

Aim: The survival rate after treatment for childhood leukaemia has greatly improved, but could result in protracted immune deficiency. This study examined the immune status of children after chemotherapy and evaluated their responses to immunisation. Methods: Subjects who had completed their treatment for acute lymphoblastic leukaemia at The Children's Hospital Reykjavík, Iceland, during 2011–2020 had blood drawn and were then immunised for influenza in October 2021. Blood was drawn again 4 weeks later and their humoral and cellular responses were measured with a haemagglutination inhibition assay and lymphocyte stimulation test. Antibodies to other immunisations were also evaluated. Results: We studied 18 patients (10 male) who had completed their treatment at 3.7–20.3 years of age (mean 9.1), 11–84 months (mean 36.9) before enrolment. Conventional immunological evaluation did not reveal notable abnormalities. The responses to several childhood vaccinations, including the pneumococcal conjugate vaccination, were adequate in most patients. Humoral responses to the influenza vaccine confirmed adequate reactions in all but one patient. Considerable variations were observed in the lymphocyte stimulations tests. Conclusion: Most patients reacted adequately to immunisation, especially against annual influenza and Streptococcus pneumoniae, reiterating the usefulness of vaccinations. The most appropriate timing for vaccination after treatment still needs to be determined. [ABSTRACT FROM AUTHOR]

Understanding the local epidemiology of feline leukaemia virus (FeLV) and feline immunodeficiency virus (FIV) in Hong Kong will inform retrovirus prevention strategies. Domestic cat hepadnavirus (DCH), a novel hepatitis-B-like virus, is commonly detected among client-owned cats in Hong Kong, but community cats have not been studied. The aims of this study were to investigate the frequency and potential risk factors for (i) FeLV and FIV among community and client-owned cats and (ii) perform molecular detection of DCH among community cats in Hong Kong. Blood samples from 713 cats were obtained from client-owned (n = 415, residual diagnostic) and community cats (n = 298, at trap-neuter-return). Point-of-care (POC) testing for FeLV antigen and feline immunodeficiency virus (FIV) anti-p15 and p24 antibodies was performed. FeLV-positive samples were progressed to p27 sandwich enzyme-linked immunosorbent assay. Whole blood DNA was tested with qPCRs for FeLV U3 and gag, and nested PCRs where additional information was required. DCH qPCR was performed on a subset of community cats (n = 193). A single, regressive, FeLV infection was detected in a client-owned cat (1/415 FeLV U3 qPCR positive, 0.2%, 95% CI 0.0–1.3%). Five/415 client-owned cats tested presumably false FeLV-antigen positive (qPCR negative). No markers of FeLV infection were detected in community cats (0/298; 0%). FIV seroprevalence was much higher in community cats (46/298, 15.4%) than in client-owned cats (13/415, 3.1%) (p < 0.001). Mixed breed was a risk factor for FIV infection in client-owned cats. Neither sex nor age were associated with FIV infection. DCH DNA was detected in 34/193 (17.6%) community cats (median viral load 6.32 × 103 copies/reaction). FeLV infection is rare in Hong Kong, negatively impacting the positive predictive value of diagnostic tests. FeLV-antigen testing remains the screening test of choice, but confirmation of a positive result using FeLV qPCR is essential. FIV infection is common in community cats and the absence of a sex predisposition, seen previously in cats managed similarly, raises questions about virus-transmission dynamics in these groups. DCH infection is very common in Hong Kong, both in client-owned and community cats, highlighting the importance of understanding the pathogenic potential of this virus for cats. [ABSTRACT FROM AUTHOR]

Summary: Mastocytosis constitutes the neoplastic proliferation of mast cells and is broadly classified into systemic mastocytosis (SM), cutaneous mastocytosis and mast cell sarcoma. SM is further partitioned into advanced (AdvSM) and non‐advanced (SM‐non‐Adv) subcategories. AdvSM includes aggressive SM (ASM), SM with an associated haematological neoplasm (SM‐AHN) and mast cell leukaemia (MCL). In 2022, two separate expert committees representing the 5th edition of the World Health Organization (WHO5) and the International Consensus (ICC) classification systems submitted revised classification criteria for SM, highlighted by the ICC‐proposed incorporation of mast cell cytomorphology in the diagnostic criteria for MCL and myeloid‐lineage restriction for the AHN component in SM‐AHN. Recent developments in SM also include the introduction of KIT‐targeting tyrosine kinase inhibitors (KITi), including midostaurin and avapritinib, both drugs have shown potent activity in reducing mast cell and mutant KIT burden and alleviating mast cell‐associated organopathy and mediator symptoms; however, their overall impact on survival or superiority over pre‐KITi era treatment options (e.g. cladribine) has not been studied in a controlled setting. In the current review, we provide a summary of recent changes in disease classification and an analysis of recent clinical trials and their impact on our current treatment approach in AdvSM. [ABSTRACT FROM AUTHOR]

In a nationwide, matched cohort study, we aimed to investigate risks of haematologic cancers among individuals tested for Borrelia burgdorferi (Bb) antibodies, and among serum Bb seropositive individuals. We identified all Bb seropositive individuals in Denmark (1993–2020) (n = 52 200) and constructed two age- and sex-matched comparison cohorts: (a) Bb seronegative controls (n = 104 400) and (b) background population controls (n = 261 000). We calculated short-term OR (aOR) (<1 month of study inclusion), and long-term hazard ratios (aHR) (>1 month after study inclusion) adjusted for age and sex. We stratified seropositive individuals on only Bb- IgM seropositive (n = 26 103), only Bb- IgG seropositive (n = 18 698), and Bb- IgM-and-IgG seropositive (n = 7399). Compared with the background population, individuals tested for Bb antibodies had increased short-term (aOR: 12.6, 95% CI: 10.1–15.6) and long-term (aHR: 1.3, 95% CI: 1.2–1.4) risk of haematologic cancers. The Bb seropositive individuals had no increased risk of haematologic cancers compared with those who tested negative for Bb, except that Bb- IgM-and-IgG seropositive individuals had increased long-term risk of chronic lymphatic leukaemia (aHR: 2.0, 95% CI: 1.2–3.4). Our results suggest that Bb antibody testing is included in the work-up of unspecific symptoms preceding diagnosis of haematologic cancers. Bb- IgM-and-IgG seropositivity was associated with a two-fold increased long-term risk of chronic lymphatic leukaemia, which warrants further investigation. [ABSTRACT FROM AUTHOR]