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Objective: To explore symptom experiences and self-management strategies from the haematological malignancy patient's perspective. Methods: A qualitative descriptive approach was used to provide a direct and comprehensive understanding of the symptoms experienced and self-management strategies during treatment among patients with haematological malignancy. Fourteen patients with haematologic malignancies who received chemotherapy at a Chinese tertiary hospital were selected using purposeful sampling. Data were collected via semi-structured interviews and one-on-one patient sessions. The collected data were analysed using the content analysis methods. Reporting adhered to the COnsolidated criteria for REporting Qualitative research (COREQ) guidelines. Results: The data from this study were categorized into four themes and eight subthemes: (1) the dynamics and complexity of symptom experience (nonlinear, and overloaded symptom burden); (2) strategies for coping with symptomatic change (actively responding to challenges, and facing symptoms negatively); (3) symptom affects interaction (symptoms affect family interactions, and symptoms affect social interactions); and (4) benefit from symptom management (promoting family relationships, and regaining a new role in society). Conclusions: Patients with haematological malignancy undergoing chemotherapy still face complex and variable symptoms, and there are still considerable challenges in symptom management. The findings underscore that health care providers should provide the necessary symptom assessment to enhance the well-being of patients based on the characteristics of the patient's symptom experience and symptom management needs at different stages of the disease.

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Chimeric antigen receptor (CAR) T-cell therapies have revolutionised the field of haematological malignancies by achieving impressive remission rates in patients with highly refractory haematological malignancies, improving overall survival. To date, six commercial anti-CD19 and anti-BCMA CAR T-cell products have been approved by the Food and Drug Administration (FDA) for the treatment of relapsed/refractory B-cell haematological malignancies and multiple myeloma. The indications for CAR T-cell therapies are gradually expanding, with these therapies being investigated in a variety of diseases, including non-malignant ones. Despite the great success, there are several challenges surrounding CAR T-cell therapies, such as non-durable responses and high-grade toxicities. In addition, a new safety concern was added by the FDA on 28 November 2023 following reports of T-cell malignancies in patients previously treated with either anti-CD19 or anti-BCMA autologous CAR T-cell therapies both in clinical trials and in the real-world setting. Since then, several reports have been published presenting the incidence and analysing the risks of other secondary malignancies after CAR T-cell therapies. In this opinion article, the current landscape of secondary malignancies after CAR T-cell therapies is presented, along with a proposed strategy for future research aiming at potentially diminishing or abrogating the risk of developing secondary malignancies after CAR T-cell therapies.

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Background: Apart from troponins, various additional biomarkers that indicate myocardial injury, inflammation, thrombosis, and other routes are being studied to improve the treatment of acute coronary syndrome (ACS). Myeloid activity has been found to be elevated in ACS, and this has sparked a great deal of interest in hematological parameters since they might offer independent insights into pathophysiology and risk assessment. Objective: The purpose of this study was to evaluate the hematological markers' prognostic ability for all intrahospital causes of mortality in individuals with an ACS diagnosis. Methods: A long-term cohort study based at an institution was done. At Jimma Medical Center, patients with an ACS diagnosis were progressively brought in between May 1, 2022, and October 31, 2023. Complete blood counts (CBC) and biochemical analysis were carried out. Multilevel mixed effect logistic regression was computed to evaluate the predictive competence of hematological indices on intrahospital mortality. Prognostic performance of hematological parameters was done using the ROC curve analysis. Result: A total of 110 patients were included, of which 99 (90 %) were diagnosed ST-elevation myocardial infarction, and 74 (67.3 %) were men. The mean age was 56 (±11) years. RDW, platelet count, and MCV were independently associated with intrahospital mortality (AOR = 1.20 with P < 0.001, AOR = 0.995 with P < 0.03, and AOR = 0.897 with P < 0.025, respectively). The predictive power of RDW-SD for intrahospital mortality was evaluated by ROC analysis, the AUC value were 0.737 (95 % CI 0.669-0.805). Conclusion: This study found that red cell distribution width, mean corpuscular volume, and platelets were predictive factors for intrahospital death in patients with ACS. Thus, it is possible to predict the prognosis of an ACS patient using hematological data.

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Chimeric antigen receptor T-cell (CAR T-cell) therapies have emerged as a promising treatment modality for several malignancies, particularly haematological malignancies, by inducing robust antitumour responses. However, CAR T-cell therapies are associated with a spectrum of adverse events, including neurological complications. We here provide a review of neurological adverse events observed in patients undergoing CAR T-cell therapy, focusing on their incidence, clinical manifestations, underlying mechanisms and potential management strategies.

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OBJECTIVES: To investigate the severe haematological involvement in children with SLE and assess its clinical associations, treatments, outcome and damage accrual. METHODS: The medical charts of children with SLE in whom haematological involvement was observed were reviewed. Severe haematological indices were defined as autoimmune haemolytic anaemia with a haemoglobin concentration < 8 g/dL, thrombocyte count < 30 000/µL, and neutrophil count < 500/µL. RESULTS: Among the 224 patients included, 102 (45.5%) displayed severe indices, predominantly at the initial involvement, and most frequently as severe anaemia in 54 (24.1%) and severe thrombocytopenia in 45 (20.1%). Disease activity did not differ according to the presence of severe disease indices. In addition, the presence of severe indices at initial involvement did not affect the damage accrual. However, a higher rate of damage (51.1% vs. 29.9%, p = 0.002) and steroid-induced damage (28.9% vs. 8.2%, p < 0.001) was evident in patients with flares of the haematological system. Regression analysis revealed that rituximab treatment during the initial episode (OR:4.5, p = 0.006) and the presence of anticardiolipin antibodies (OR:2.3, p = 0.014) significantly increases the odds for haematological system flare. However, severe indices at initial involvement did not increase the odds of a haematological flare. CONCLUSION: Severe haematological indices at onset are common but not related with disease outcomes. Prevention of flares is important to improve outcomes, and a more rigorous maintenance strategy would benefit most to children who display haematological indices refractory to conventional immunosuppressants and those with anti-cardiolipin antibodies.

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OBJECTIVE: Osimertinib plays a crucial role in patients with non-small cell lung cancer (NSCLC). However, the haematological toxicities caused by osimertinib in such a population have not been well characterised. This analysis was performed to determine the incidence of osimertinib-related haematological toxicity in patients with NSCLC. METHOD: A literature search was conducted in PubMed, Embase, Cochrane Library and Web of Science. Eligible studies were included to describe the pooled incidences of anaemia, neutropenia and thrombocytopenia secondary to osimertinib in NSCLC patients. RESULTS: 1288 patients from 10 studies were enrolled in this study. The overall incidences of osimertinib-related all-grade anaemia, neutropenia and thrombocytopenia in NSCLC patients were 21.1% (95% CI 10.9% to 33.3%), 14.6% (95% CI 5.9% to 26.1%) and 28.4% (95% CI 12.4% to 47.6%), respectively. In items of high-grade haematological toxicities, there were 0.5% (95% CI 0.1% to 1.1%) for anaemia, 2.0% (95% CI 0.3% to 4.6%) for neutropenia and 0.4% (95% CI 0% to 1.1%) for thrombocytopenia. CONCLUSIONS: There is non-negligible haematological toxicity associated with osimertinib, and it should be taken seriously.

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The optimal therapeutic approach for relapsed/refractory (R/R) Waldenström's Macroglobulinaemia (WM) has not been clearly defined, especially after treatment with chemoimmunotherapy (CIT) and covalent Bruton's tyrosine kinase inhibitors (cBTKi). The PembroWM trial is a multi-centre, phase II, single-arm study assessing the safety, tolerability and efficacy of rituximab with pembrolizumab in R/R WM patients who had received at least one prior line of treatment, with all having relapsed post-CIT and most also exposed to cBTKi. A total of 17 patients were enrolled, with a median age of 70, and median of three prior lines of therapy with 15 either refractory or intolerant of a cBTKi. A significant proportion was identified as genomically high risk with BTKC481, CXCR4 and MYD88 L265P wild-type aberrations. Twenty-four-week overall response rate was 50% (60% CI 39.3%-60.7%), and median duration of response was 11.6 months (IQR: 6.3-17). The median progression-free survival was 13.6 months (95% CI 3-19.8), and the median overall survival (OS) was not reached. Treatment was well tolerated, with minimal numbers of immune-mediated AEs typically seen with checkpoint inhibitors. PembroWM is the first study to evaluate the feasibility of PD-1 axis modulation in WM and has shown that in combination with Rituximab the combination is safe and deliverable.

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In this study, we employed the dithiothreitol-based protein equalisation technique and analytical proteomics to better understand myeloma diseases by comparing the proteomes of pellets and supernatants formed upon application of DTT on serum samples. The number of unique proteins found in pellets was 252 for healthy individuals and 223 for multiple myeloma patients. The comparison of these proteomes showed 97 dysregulated proteins. The unique proteins found for supernatants were 264 for healthy individuals and 235 for multiple myeloma patients. The comparison of these proteomes showed 87 dysregulated proteins. The analytical proteomic comparison of both groups of dysregulated proteins is translated into parallel dysregulated pathways, including chaperone-mediated autophagy and protein folding, addressing potential therapeutic interventions. Future research endeavours in personalised medicine should prioritize refining analytical proteomic methodologies using serum dithiothreitol-based protein equalisation to explore innovative therapeutic strategies. We highlight the advanced insights gained from this analytical strategy in studying multiple myeloma, emphasising its complex nature and the critical role of personalised, targeted analytical techniques in enhancing therapeutic efficacy in personalised medicine.

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Ubiquitin like modifier activating enzyme 1 (UBA1) plays an important role in immune regulation and cellular function. However, the functional mechanism and role of UBA1 in pan-cancer have not been fully elucidated and its value in haematological tumours (diffuse large B cell lymphoma (DLBC/DLBCL) and acute myeloid leukaemia (AML/LAML)) has not been explored. We conducted a comprehensive analysis of the functional mechanism and role of UBA1 in pan-cancer using multiple databases, including differential expression analysis, clinical pathological staging analysis, prognosis analysis and immune analysis. Then, we confirmed the function of UBA1 in haematological tumours through cell experiments. The results showed that the expression of UBA1 was significantly increased in most cancers and the differential expression of UBA1 was mainly concentrated in digestive tumours, haematological tumours and brain tumours. Moreover, the high expression of UBA1 had poor prognosis in most tumours, which may be related to its involvement in various cancer-related pathways such as cell cycle, as well as its methylation level, protein phosphorylation level, immune cell infiltration and immune therapy response. Cell experiments have confirmed that UBA1 can significantly regulate the cycle progression and apoptosis of DLBCL cells and AML cells. Therefore, UBA1 may be a potential therapeutic target for haematological tumours. In summary, our study not only comprehensively analysed the functional mechanisms and clinical value of UBA1 in pan-cancer, but also validated for the first time the regulatory role of UBA1 in haematological tumours.

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BACKGROUND: Invasive fungal infections (IFI) are a relevant cause of morbidity and mortality among patients with haematological neoplasms (HMs). Since 2002, a classification of IFI based on host factors, clinical and radiological features and mycological tests was published for research purpose. OBJECTIVES: These criteria are widely used in clinical practice to identify patients at risk for IFI. The aim of the study was to evaluate the clinical applicability of EORTC/MSG 2008 criteria for the diagnosis of IFI in daily practice. PATIENTS/METHODS: This multicentre, non-interventional, observational, prospective study gathered all consecutive inpatients with HMs in which an intravenous antifungal treatment was started. Exclusion criteria were a previous or concomitant transplant procedure, outpatient status and oral antifungal therapy. EORTC/MSG 2008 criteria were used to classify patients at the beginning of antifungal therapy and at 30 days. An independent board reviewed the classification of IFI given by local clinicians at T0 and T30. RESULTS: The highest percentage of agreement was found for possible IFI (96%), while a lower agreement was reported for proven IFI (74%), and the highest variability was observed for probable IFI (56%). At T30, the board re-evaluation confirmed a strict agreement for possible IFI only (98%). Among 306 patients classified as possible, 156 (51%) patients showed non-typical radiological findings and 45 (15%) patients presented host factors only. CONCLUSIONS: In real life, the EORTC/MSG criteria can be applicable only for possible IFI. As non-typical radiological findings are reported in possible IFI, introducing a new IFI category should be considered.

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Arterial thrombosis contributes to some of the most frequent causes of mortality globally, such as myocardial infarction and stroke. Platelets are essential mediators of physiological haemostasis and pathological thrombosis. Platelet activation is controlled by a multitude of signalling pathways. Upon activation, platelets shed platelet-derived extracellular vesicles (pEVs). In this Special Issue: Extracellular Vesicles, Moon et al. investigate the impact of various platelet agonists (thrombin, ADP, collagen) on the proteome of pEVs. The study demonstrates that pEVs exhibit an agonist-dependent altered proteome compared to their parent cells, with significant variations in proteins related to coagulation, complement, and platelet activation. The study observes the rapid generation of pEVs following agonist stimulation with specific proteome alterations that underscore an active packaging process. This commentary highlights the implications of their findings and discusses the role of pEV cargo in cardiovascular disease with potential novel therapeutic and diagnostic opportunities.

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Paroxysmal nocturnal haemoglobinuria (PNH) is a rare, potentially life-threatening haematological disease characterised by chronic complement-mediated haemolysis with multiple clinical consequences that impair quality of life. This post hoc analysis assessed haematological and clinical responses to the first targeted complement C3 inhibitor pegcetacoplan in patients with PNH and impaired bone marrow function in the PEGASUS (NCT03500549) and PRINCE (NCT04085601) studies. For patients with impaired bone marrow function, defined herein as haemoglobin <10 g/dL and absolute neutrophil count <1.5 × 109 cells/L, normalisation of the parameters may be difficult. Indeed, 20% and 43% had normalised haemoglobin in PEGASUS and PRINCE, respectively; 60% and 57% had normalised LDH, and 40% and 29% had normalised fatigue scores. A new set of parameters was applied using changes associated with clinically meaningful improvements, namely an increase in haemoglobin to ≥2 g/dL above baseline, decrease in LDH to ≤1.5× the upper limit of normal, and an increase in fatigue scores to ≥5 points above baseline. With these new parameters, 40% and 71% of PEGASUS and PRINCE patients had improved haemoglobin; 60% and 71% had an improvement in LDH, and 60% and 43% had an improvement in fatigue scores. Thus, even patients with impaired bone marrow function may achieve clinically meaningful improvements with pegcetacoplan.

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BACKGROUND: Examining the distribution of biochemical and haematological tests in different age groups of rural population is necessary to ensure that health care facilities are equipped to address the prevalent health conditions and manage age-related illness effectively. Hence, this study is aimed at seeing the distributions of blood biochemical and haematological parameters in rural population. METHODS: This cross-sectional study investigated the distribution of 26 different haematological and biochemical parameters in longitudinal cohort study (Srinivaspura Aging, NeuoSenescence and COGnition - SANSCOG), from the villages of Srinivaspura, Kolar district, India. A total of 2592 participants (1240 males and 1352 females), aged ≥45 years who are cognitively healthy were included for the analysis. Mean, 2.5th, 5th, 25th, 50th, 75th, 95th and 97.5th percentiles were calculated for the entire sample. Additionally, median and percentiles were determined for both gender and age categories (45-54, 55-64, 65-74, and ≥75 years). RESULTS: We observed the distinct distributions of various haematological and biochemical parameters, with elevated levels of glycaemic, lipid, liver, and thyroid parameters. CONCLUSION: Findings revealed the notable variations from the established reference ranges, indicating the potential undiagnosed cases and highlighting the gaps in health awareness and health seeking behaviour.

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Haemolytic anaemia represents a risk factor for the development of pulmonary hypertension (PH), currently classified as World Health Organization group 5 PH, and data regarding appropriate therapeutic strategy are limited. A total of 28 patients, 85.7% with thalassaemia and 14.3% with sickle cell disease, with a diagnosis of PH confirmed by right heart catheterization were included in the study. The patients were divided into three groups according to the PH haemodynamic definition and overall diagnostic approach: 42.9% had precapillary PH (pulmonary arterial hypertension-PAH group), 25% had post-capillary PH, and 32.1% had chronic thromboembolic PH (CTEPH) (29% of b-thalassemia and 50% of SCD patients). The therapeutic approach in each group and its impact on the outcome and haemodynamics were recorded. PAH-specific drug therapy received 82.1% of patients, and balloon pulmonary angioplasty (BPA) was performed in six patients with CTEPH. There were statistically significant differences in baseline mPAP and PVR values between the CTEPH-haemolytic anaemia group and other groups. PAH-specific drug therapy resulted in haemodynamic improvement for the PAH group. Patients who underwent BPA had improved pulmonary haemodynamics. The median survival time was 162 months, and the survival rate was 1 year-100%; 2, 3, 4, 5, and 6 years-96%; 9 years-90%; and 13 years-78%. In patients with haemolytic anaemia, the wide spectrum of induced PH highlighted the importance of a correct predominant diagnosis. BPA in CTEPH patients and specific-PAH drug therapy for PAH patients represent potential therapeutic strategies; however, the management should be offered in expert PH centres under individualized approaches for patients.

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The effect of helminthiasis on host immunity is a neglected area of research, particularly in tuberculosis (TB) infection. This study aimed to evaluate the effect of helminthiasis on immunological and haematological parameters in newly diagnosed TB patients in Bobo-Dioulasso. After all biological analyses, we formed three subpopulations: group 1 (n = 82), as control, were participants without helminthic or Mycobacterium tuberculosis complex infection (Mtb-/Helm-), group 2 (n = 73) were TB patients without helminthic infection (Mtb+/Helm-), and group 3 (n = 22) were TB patients with helminthic infection (Mtb+/Helm+). The proportion of helminth coinfection was 23.16% (22/95) in TB patients, and Schistosoma mansoni infection was found in 77.3% (17/22) cases of helminthiasis observed in this study. A low CD4 T cell count and a low CD4:CD8 ratio were significantly associated with concomitant infection with helminths and the Mtb complex (Mtb+/Helm+) compared to the other groups (p < 0.05). However, there was no statistically significant difference in the CD8 median among the three participating groups (p > 0.05). Lymphopenia, monocytosis, thrombocytosis, and hypochromic microcytic anaemia were the haematological defects observed in the Mtb+/Helm+ and Mtb+/Helm- patients. Exploring these types of immune-haematological biomarkers would be a valuable aid in diagnosing and a better follow-up and monitoring of the tuberculosis-helminthiasis coinfection.

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The present study aims to assess the acute and subacute toxicity of the hydro-alcoholic extracts of Anchusa strigosa (leaves) and the aerial parts of Zataria multiflora Boiss in Wistar albino rats. The crude extracts of Anchusa strigosa (leaves) and the aerial parts of Zataria multiflora Boiss were prepared in 70% ethanol. Systematic tests for acute toxicity were performed at varying dosages of 100, 250, and 500 mg/kg, while for subacute toxicity, a dose of 600 mg/kg was orally given to Wistar albino rats. At the end of acute and sub-acute toxicity studies, biochemical parameters, hematological analysis, and histopathological analysis showed no significant difference in the body weight, abnormalities, or organ damage of the rats compared to the untreated rats (control). Also, there were no results of death recorded in rats. These findings indicated that the medium-term oral administration of Anchusa strigosa (leaves) and the aerial parts of Zataria multiflora Boiss after the treatment does not cause toxicity and provides assurance regarding their suitability for potential therapeutic applications in both acute and subacute forms.

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BACKGROUND: Malaria is a life-threatening parasitic disease typically transmitted through the bite of an infected Anopheles mosquito. There is ample evidence showing the potential of malaria infection to affect the counts of lymphocyte subpopulations in the peripheral blood, but the extent of alteration might not be consistent in all geographical locations, due to several local factors. Although Ghana is among the malaria-endemic countries, there is currently no available data on the level of alterations that occur in the counts of lymphocyte subpopulations during P. falciparum malaria infection among adults. AIM: The study was to determine the immunophenotypic alterations in the level of peripheral blood lymphocytes and their subsets in adults with uncomplicated P. falciparum malaria infection and apparently healthy participants. METHODS: The study was a cross-sectional comparative study conducted in two municipalities of the Volta region of Ghana. Blood samples were collected from study participants and taken through serology (P. falciparum/Pan Rapid Diagnostic Kits), microscopy (Thick and thin blood films) and Haematological (Flow cytometric and Full blood count) analysis. RESULTS: A total of 414 participants, comprising 214 patients with malaria and 200 apparently healthy individuals (controls) were recruited into this study. Parasite density of the malaria patients ranged from 75/µL to 84,364/µL, with a mean of 3,520/µL. It was also observed that the total lymphocytes slightly decreased in the P. falciparum-infected individuals (Mean ± SD: 2.08 ± 4.93 × 109/L) compared to the control group (Mean ± SD: 2.47 ± 0.80 × 109/L). Again, there was a significant moderate positive correlation between parasite density and haematocrit levels (r = 0.321, p < 0.001). Apart from CD45 + T-cells, more people in the control group had normal values for the lymphocyte subsets measured compared to the malaria patients. CONCLUSIONS: From the results obtained, there was high parasite density among the malaria patients suggestive of high intensity of infection in the case group. The malaria patients again showed considerable haematological alterations in lymphocyte sub-sets and the parasite density appeared to be strongly associated with CD4 + T-cell reduction. Also, the parasite density significantly associated with decreasing haematocrit levels. This indicates that lymphocyte subset enumeration can be used to effectively support malaria diagnosis.

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Cytomegalovirus reactivation (CMVr) and bloodstream infections (BSI) are the most common infectious complications in patients after allogeneic haematopoietic stem cell transplantation (allo-HSCT). Both are associated with great high morbidity whilst the BSI is the leading cause of mortality. This retrospective study evaluated the incidence of CMVr and BSI, identified associated risk factors, assessed their impact on survival in allo-HSCT recipients during the first 100 days after transplantation. The study comprised 500 allo-HSCT recipients who were CMV DNA-negative and CMV IgG-positive before allo-HSCT. Amongst them, 400 developed CMVr and 75 experienced BSI within 100 days after allo-HSCT. Multivariate regression revealed that graft failure and acute graft-versus-host disease were significant risk factors for poor prognosis, whereas CMVr or BSI alone were not. Amongst all 500 patients, 56 (14%) developed both CMVr and BSI in the 100 days after HSCT, showing significantly reduced 6-month overall survival (p = 0.003) and long-term survival (p = 0.002). Specifically, in the initial post-transplant phase (within 60 days), BSI significantly elevate mortality risk, However, patients who survive BSI during this critical period subsequently experience a lower mortality risk. Nevertheless, the presence of CMVr in patients with BSI considerably diminishes their long-term survival prospects. This study provides real-world data on the impact of CMVr and BSI following transplantation on survival, particularly in regions such as China, where the prevalence of CMV IgG-positivity is high. The findings underscore the necessity for devising and executing focused prevention and early management strategies for CMVr and BSI to enhance outcomes for allo-HSCT recipients.

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Background: Haematological abnormalities are common among tuberculosis patients but there is dearth of information on their value as prognostic markers in Multidrug resistant tuberculosis patients. This study examined the association between complete blood count variables and drug resistant tuberculosis. Materials and methods: Nighty (90) consenting adults comprising 30 Drug Resistant Tuberculosis patients (DR-TB), 30 Drug susceptible tuberculosis patients (DS-TB) and 30 healthy participants were recruited in this study. Ethical approval was obtained from Oyo State Ministry of Health Institutional Review Board while patients' demographic data were collected using structured questionnaire. Five milliliters (5mL) of blood samples were collected in EDTA bottle. Haematological parameters were analysed using impedance technique and Mindary-BG5380 5-part automated system. Result: The mean hemoglobin levels were significantly lower in DR-TB patients (11.70 ± 2.73 g/dL) than in DS-TB patients (8.33 ± 9.56 fL), with a mean difference of -3.37 ± 12.29 g/dL. The mean MCH and MCHC levels were also slightly lower in DR-TB patients (26.17 ± 3.44 pg and 30.41 ± 1.92 g/dL, respectively), but the differences were not statistically significant. The WBC count was similar in both groups (8.20 ± 3.80 × 10^9 /L and 8.45 ± 3.63 × 10^9 /L, respectively). Conclusion: The mean hemoglobin levels were significantly lower in DR-TB patients than in DS-TB patients which may be due to the increased inflammation associated with DR-TB. The WBC count was similar in both groups, suggesting that the immune system is responding similarly to the infection in both DR-TB and DS-TB patients. Recommendation: In the meantime, healthcare providers should be aware of these potential differences and use them to inform their diagnosis and treatment of patients with tuberculosis.

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