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Summary Early‐phase trials of venetoclax in children and teenagers/young adults with leukaemia have yielded promising results, but there remains a paucity of real‐world data. To address this, we report a cohort of 41 children treated with venetoclax for a range of haematological malignancies, demonstrating complete remission in 43.6%, with most achieving minimal residual disease (MRD) negativity. Venetoclax was particularly effective as a bridge to transplant, with bridging successful in 75% of patients. Patients with MRD <1% at initiation of venetoclax were more likely to achieve MRD negativity (81.8% vs. 34.5%, p = 0.007) and had improved overall survival (54.5% vs. 17.9%, p = 0.004). [ABSTRACT FROM AUTHOR]

Summary Philadelphia chromosome (Ph)‐like acute lymphoblastic leukaemia (ALL) is a high‐risk subtype with a gene expression profile similar to Ph‐positive ALL, due to activation of tyrosine kinase signalling. To understand the clinical implications of Ph‐like ALL, this single‐centre retrospective study evaluates outcomes in 268 adults, largely Hispanic ALL patients treated between 2013 and 2024, with a subgroup analysis of 139 haematopoietic stem cell transplantation (HSCT) patients. ALL subtypes included 68 (25.4%) Ph‐like, 89 (33.2%) Ph‐positive, and 111 (41.4%) Ph‐negative. Ph‐like patients were the youngest age at diagnosis (p = 0.007), most likely to have refractory disease (p < 0.001), and least likely to achieve minimal residual disease (MRD) negativity after induction (p = 0.031). Relative to Ph‐negative ALL, Ph‐like achieved worse event‐free survival (EFS) (HR = 1.66; 95% CI 1.12–2.46; p = 0.012), whereas Ph‐positive had improved EFS (HR = 0.60; 95% CI 0.38–0.93; p = 0.024) and cumulative incidence of relapse (CIR) (HR = 0.59; 95% CI 0.35–0.99; p = 0.046). Within the transplant subgroup, Ph status did not impact disease‐free survival (DFS), CIR, or overall survival (OS). However, patients who received blinatumomab within 1‐year pre‐HSCT had improved DFS (HR = 0.43; 95% CI 0.20–0.94; p = 0.034) and CIR (HR = 0.26; 95% CI 0.09–0.75; p = 0.13). In conclusion, our data suggest that Ph‐like is less likely to respond to standard induction therapy and HSCT may result in similar survival outcomes to Ph‐negative ALL. [ABSTRACT FROM AUTHOR]

Summary Acute lymphoblastic leukaemia (ALL) in 20%–30% of adult patients contains the Philadelphia (Ph+) chromosome. Historically, Ph+ ALL denoted a markedly inferior outcome and long‐term survival in the absence of an allograft was uncommon. However, the advent of targeted therapy directed against the BCR::ABL1 fusion protein with various tyrosine kinase inhibitors (TKIs) has markedly improved the prognosis, resulting in a number of treatment controversies in allograft‐eligible patients. Which is the best TKI to use in induction? What is the clinical relevance of the subdivision of Ph+ ALL into multilineage vs lymphoid types? Do all patients in first morphological complete remission (CR1) after induction and consolidation with chemotherapy/TKI require an allograft? If not, what risk factors predict a poor outcome without an allograft? Can chemotherapy‐free approaches, such as blinatumomab in conjunction with more potent TKIs, obviate the need for an allograft in high‐risk patients? What is the best strategy to deal with persistent or emerging minimal residual disease both pre‐ and post‐transplant? Is maintenance TKI indicated in all patients post allograft? Can salvage therapy and a subsequent allograft cure patients who relapse after not being transplanted in CR1? This manuscript reviews the latest data influencing contemporary management and discusses these controversies. [ABSTRACT FROM AUTHOR]

Summary Addition of molecular data to prognostic models has improved risk stratification of myelodysplastic neoplasms (MDS). However, the role of molecular lesions, particularly in the group of low‐risk disease (LR‐MDS), is uncertain. We evaluated a set of 227 patients with LR‐MDS. Overall survival (OS) and probability of leukaemic progression were the main endpoints. RUNX1 was associated with lower OS and SF3B1 with a reduced risk of death (HR: 1.7, 95% CI, 1.1–2.9; p = 0.05; and HR: 0.23, 95% CI 0.1–0.5; p < 0.001; respectively). TP53 and RUNX1 mutations were predictive covariates for the probability of leukaemic progression (p < 0.001). Blast percentage, neither analysed as categorical (<5% vs. 5%–9%; HR: 1.3, 95% CI, 0.7–2.9; p = 0.2) nor as a continuous variable (HR: 1.07, 95% CI, 0.9–1.1; p = 0.07), had impact on survival or probability of progression (sHR: 1.05, 95% CI, 0.9–1.1; p = 0.2). These results retained statistical significance when analysis was restricted to the definition of LR‐MDS according to the WHO 2022 and ICC classifications (<5% blasts). Thus, with the incorporation of molecular data, blast percentage happens to lose clinical significance both for survival and probability of progression in the group of patients with LR‐MDS. [ABSTRACT FROM AUTHOR]

Background: Bleeding is a primary outcome for many transfusion‐related trials in acute leukaemia (AL) patients, typically graded using the World Health Organisation (WHO) bleeding scale (clinically significant bleed (CSB) is ≥grade 2). This composite outcome fails to differentiate minor bleeds that may not be significant, poorly represents the total burden of bleeding and lacks input from healthcare providers (HCPs) and patients. As part of a multi‐step project to create a better bleeding tool for trials, our objective was to identify HCPs' perspectives on the components of CSB in AL patients. Study Design and Methods: Using qualitative description, we interviewed 19 physicians and nurses who care for AL patients undergoing induction chemotherapy. Participants were recruited from professional organisations, networks and social media. An inductive approach to conventional content analysis was used. Results: HCPs identified features of CSB as the anatomical site of bleeding, amount of bleeding, need for intervention and changes in vital signs. Using these characteristics, bleeding events were categorised into three groups: clinically significant, could evolve into a CSB and not clinically significant. HCPs considered the patient's condition, bleeding history and clinical intuitions when deciding whether a bleed could escalate into serious bleeding. Discussion: Using data from HCPs, we categorised bleeds as clinically significant, could evolve into a CSB, and not significant. A study of patients' perspectives on the importance of different kinds of bleeding is the next step to creating a bleeding definition that is informed by evidence, clinicians and patients. [ABSTRACT FROM AUTHOR]

Summary: Therapy‐related acute lymphoblastic leukaemia (tr‐ALL) is a disease entity attributed to previous exposure to chemotherapy and/or radiation for antecedent malignancy. There is observed female predominance for tr‐ALL, likely due to high prevalence and excellent curable rate for non‐metastatic breast cancer as well as the frequent use of carcinogenic agents as part of adjuvant therapy. Here, we reviewed 37 women with diagnosis of ALL following breast cancer treatment with focus on cytogenetic categorization. Philadelphia chromosome positivity (Ph+), KMT2A alterations and other cytogenetic change groups were observed in 32%, 22% and 46% of patients respectively. Median overall survival (OS) and relapse‐free survival (RFS) were 19.4 and 12.9 months, overall while both OS and RFS were superior in tr‐ALL with Ph+ disease compared to KMT2Ar and other cytogenetics respectively. Seventeen (45.9%) patients underwent consolidative allogeneic haematopoietic cell transplantation (alloHCT) in CR1 out of which 4 (24%) relapsed following transplant. Both OS and RFS were superior in the KMT2Ar cytogenetics group following alloHCT. Ph chromosome represents the largest genetic entity of tr‐ALL following breast cancer therapy, and it may be associated with superior survival outcomes while KMT2Ar may be associated with poorer outcomes that can perhaps be mitigated by alloHSCT. [ABSTRACT FROM AUTHOR]

Background: Acute leukaemias (AL) are life-threatening blood cancers that can be potentially cured with treatment involving myelosuppressive, multiagent, intensive chemotherapy (IC). However, such treatment is associated with a risk of serious infection, in particular invasive fungal infection (IFI) associated with prolonged neutropenia. Current practice guidelines recommend primary antifungal (AF) prophylaxis to be administered to high-risk patients to reduce IFI incidence. AFs are also used empirically to manage prolonged neutropenic fever. Current strategies lead to substantial overuse of AFs. Galactomannan (GM) and β-D-glucan (BG) biomarkers are also used to diagnose IFI. Combining both biomarkers may enhance the predictability of IFI compared to administering each test alone. Currently, no large-scale randomised controlled trial (RCT) has directly compared a biomarker-based diagnostic screening strategy without AF prophylaxis to AF prophylaxis (without systematic biomarker testing). Methods: BioDriveAFS is a multicentre, parallel, two-arm RCT of 404 participants from UK NHS Haematology departments. Participants will be allocated on a 1:1 basis to receive either a biomarker-based antifungal stewardship (AFS) strategy, or a prophylactic AF strategy, which includes existing standard of care (SoC). The co-primary outcomes will be AF exposure in the 12-month post randomisation and the patient-reported EQ-5D-5L measured at 12-month post randomisation. Secondary outcomes will include total AF exposure, probable/proven IFI, survival (all-cause mortality and IFI mortality), IFI treatment outcome, AF-associated adverse effects/events/complications, resource use, episodes of neutropenic fever requiring hospital admission or outpatient management, AF resistance in fungi (non-invasive and invasive) and a Desirability of Outcome Ranking. The trial will have an internal pilot phase during the first 9 months. A mixed methods process evaluation will be integrated in parallel to the internal pilot phase and full trial, aiming to robustly assess how the intervention is delivered. Cost-effectiveness analysis will also be performed. Discussion: The BioDriveAFS trial aims to further the knowledge of strategies that will safely optimise AF use through comparison of the clinical and cost-effectiveness of a biomarker-led diagnostic strategy versus prophylactic AF to prevent and manage IFI within acute leukaemia. The evidence generated from the study will help inform global clinical practice and approaches within antifungal stewardship. Trial registration: ISRCTN11633399. Registered 24/06/2022. [ABSTRACT FROM AUTHOR]

Summary: Despite advancements in utilizing genetic markers to enhance acute myeloid leukaemia (AML) outcome prediction, significant disease heterogeneity persists, hindering clinical management. To refine survival predictions, we assessed the transcriptome of non‐acute promyelocytic leukaemia chemotherapy‐treated AML patients from five cohorts (n = 975). This led to the identification of a 4‐gene prognostic index (4‐PI) comprising CYP2E1, DHCR7, IL2RA and SQLE. The 4‐PI effectively stratified patients into risk categories, with the high 4‐PI group exhibiting TP53 mutations and cholesterol biosynthesis signatures. Single‐cell RNA sequencing revealed enrichment for leukaemia stem cell signatures in high 4‐PI cells. Validation across three cohorts (n = 671), including one with childhood AML, demonstrated the reproducibility and clinical utility of the 4‐PI, even using cost‐effective techniques like real‐time quantitative polymerase chain reaction. Comparative analysis with 56 established prognostic indexes revealed the superior performance of the 4‐PI, highlighting its potential to enhance AML risk stratification. Finally, the 4‐PI demonstrated to be potential marker to reclassified patients from the intermediate ELN2017 category to the adverse category. In conclusion, the 4‐PI emerges as a robust and straightforward prognostic tool to improve survival prediction in AML patients. [ABSTRACT FROM AUTHOR]

Summary: Physiologically based pharmacokinetic (PBPK) modelling is an alternative modelling technique that is increasingly used in pharmacokinetics. Due to its nature, it can be complementarily employed to population pharmacokinetics, especially when it comes to small population size. Here, we report the proof of concept of its application to accurately describe the pharmacokinetics of a recombinant L‐asparaginase in paediatric patients with acute lymphoblastic leukaemia. Data from two randomized, double‐blind, phase II/III clinical studies (MC‐ASP.4/ALL; MC‐ASP.5/ALL) were included to setup and evaluate the final model, respectively. Final population values for basic pharmacokinetic parameters were calculated (clearance: 0.0569 L/h/19.5 kg, volume of distribution: 1.251 L, half‐life: 18.5 h, trough concentration: 140.9 IU/L). Pharmacokinetic parameter prediction as well as predictive performance of the model proofed to be comparable to a separately developed population pharmacokinetic model with 13% deviation in predicted median L‐asparaginase trough levels. To the best of our knowledge, this is the first whole‐body PBPK model of a non‐antibody therapeutic protein. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to assess the prognostic significance of various morphological markers of chromosomal instability (CI). Design: This is a cross-sectional analytical study. Setting: Single centre study from the Department of Pathology of a tertiary care centre in India. Participants: The study included samples of bone marrow aspirates (BMA) and biopsies of patients with acute leukaemia (AL) and myelodysplastic syndrome (MDS) performed between June 2019 and June 2021. Inadequate samples were excluded. We included 178 samples from 80 cases. Interventions: BMA and biopsies slides examined for CI markers like chromatin bridges, multipolar mitosis, nuclear budding, micronuclei, laggards, chromatin string (CS) and nuclear heterogeneity (NH). CI markers were correlated with the type, severity and prognosis of acute leukaemia and MDS. Main outcome measures: Evaluation of CI markers as prognostic markers in AL and MDS. Results: We included B-cell ALL (35), AML (11), MDS (04), relapse of AL (12), and remission of AL (116). All CI markers were significantly increased in AL and MDS compared to the remission group. All CI markers were significantly higher in non-responders to therapy than in responders. In regression analysis, the median (IQR) values of CS and NH were significantly higher among non-survivors than survivors. Conclusion: CI markers of morphology are significantly associated with poor prognosis, including Non-survival of the disease. These markers are easy to identify and cost-effective. We recommend incorporating morphological markers of CI in routine reporting of haematological malignancies to assist in prognostication before reports from sophisticated techniques are available. [ABSTRACT FROM AUTHOR]

Aims: To report the clinicopathological features of Kikuchi disease in patients with acute leukaemia, emphasising similarities among cases. Methods and results: In a cohort of 454 Kikuchi disease patients, we identified three cases of concurrent acute leukaemia. These patients shared similar clinical traits, with Kikuchi disease emerging approximately a month after induction chemotherapy onset, featuring neck‐region lymphadenopathy. Notably, two patients were middle‐aged, deviating from the typical age distribution of Kikuchi disease. Histologically, these cases aligned with typical Kikuchi disease. Negative immunohistochemical stains (CD34, CD117, ERG, TdT) indicated the absence of extramedullary leukaemic infiltration. Herpes simplex virus immunohistochemical staining was also negative. Significantly, a human leucocyte antigen (HLA) association was observed in these three cases. HLA‐B*15:01, C*04:01, and DRB1*04:06 were more prevalent in these patients compared to the general population (compared with three independent control cohorts: Taiwanese Han Chinese (n = 504), Tzu Chi Taiwanese bone marrow donors (n = 364) and Hong Kong Chinese (n = 5266)). Conclusions: Our study underscores the unique link between Kikuchi disease and acute leukaemia, characterised by specific features and HLA associations. This underlines Kikuchi disease as a possible differential diagnosis in pertinent clinical scenarios. Furthermore, this syndrome offers insights into postchemotherapy immunology in acute leukaemia, enhancing comprehension. [ABSTRACT FROM AUTHOR]

In their paper, using zebrafish models, Gioacchino et al. have demonstrated the GATA2 haploinsufficiency, the genetic hallmark of GATA2 deficiency syndrome, promotes erythroid and myeloid cytopenia, and have discovered a self‐regulatory mechanism to compensate GATA2 levels and protein function. Commentary on: Gioacchino et al. GATA2 heterozygosity causes an epigenetic feedback mechanism resulting in myeloid and erythroid dysplasia. Br J Haematol 2024;205:580‐593. [ABSTRACT FROM AUTHOR]

Aims: Azathioprine (AZA) and 6‐mercaptopurine are prescribed in acute lymphoblastic leukaemia (ALL) and inflammatory bowel diseases (IBD). Metabolism to active 6‐thioguanine (6TGN) and 6‐methylmercaptopurine nucleotides (6MMPN) is variable but therapeutic drug monitoring (TDM) remains debatable. This study reports on factors impacting on red blood cell (RBC) metabolites concentrations in children to facilitate TDM interpretation. Methods: The first paediatric TDM samples received during year 2021 were analysed, whatever indication and thiopurine drug. Target concentration ranges were 200–500, <6000 pmol/8 × 108 RBC for 6TGN and 6MMPN. Results: Children (n = 492) had IBD (64.8%), ALL (22.6%) or another autoimmune disease (12.6%): mean ages at TDM were 7.5 in ALL and 13.7 years in IBD (P <.0001). ALL received 6‐mercaptopurine (mean dose 1.7 mg/kg/d with methotrexate), IBD received AZA (1.9 mg/kg/d with anti‐inflammatory drugs and/or monoclonal antibodies). Median 6TGN and 6MMPN concentrations were 213.7 [interquartile range: 142.5; 309.6] and 1144.6 [419.4; 3574.3] pmol/8 × 108 RBC, 38.8% of patients were in the recommended therapeutic range for both compounds. Aminotransferases and blood tests were abnormal in 57/260 patients: 8.1% patients had high alanine aminotransaminase, 3.4% of patients had abnormal blood count. Factors associated with increased 6TGN were age at TDM and thiopurine methyltransferase genotype in ALL and AZA dose in IBD. The impact of associated treatment in IBD patients was also significant. Conclusion: TDM allowed identification of children who do not reach target levels or remain over treated. Including TDM in follow‐up may help physicians to adjust dosage with the aim of reducing adverse effects and improve treatment outcome. [ABSTRACT FROM AUTHOR]

Granulocytic sarcoma is a myeloid neoplasm that can occur in isolation or in association with acute leukaemia. The temporal bone represents a sanctuary site for myeloid progenitors: granulocytic sarcoma may develop in this location before or concomitantly with the onset of acute leukaemia. This atypical presentation with clinical and radiological data that closely mimic those of cholesteatoma often delays an accurate diagnosis. We here describe the clinical case of a 28-year-old male with granulocytic sarcoma of the external auditory canal that preceded the relapse of promyelocytic leukaemia. [ABSTRACT FROM AUTHOR]

Purpose: To longitudinally investigate choroidal and choriocapillaris perfusion metrics and the number of choroidal hyperreflective foci (HRF) in patients with acute leukaemia (AL) before and after disease remission and to correlate these metrics with systemic parameters during active disease. Methods: Prospective, longitudinal study of 26 eyes of 14 AL patients. All patients underwent optical coherence tomography (OCT) and OCT‐angiography (OCTA) in the acute phase. Subfoveal choroidal thickness (CT), total, luminal and stromal choroidal area (TCA, LCA, SCA), choroidal vascularity index (CVI), choriocapillaris flow deficits (cFD) density, and choroidal HRF number were computed. In a subset, the measurements were repeated after AL remission. Age‐ and gender‐matched 26 healthy controls were recruited for cross‐sectional comparisons. Results: Patient's mean age was 59 ± 12 years. The TCA, LCA, SCA and choroidal HRF number were significantly higher in patients than controls (p = 0.028, p = 0.044, p = 0.024 and p = 0.001, respectively). Lower haemoglobin levels were associated with lower CT (r = 0.58, p = 0.008). Higher D‐dimer values were associated with lower TCA (r = −0.52, p = 0.008), lower LCA (r = −0.50, p = 0.006), higher cFD density (r = 0.41, p = 0.044) and higher choroidal HRF number (r = 0.47, p = 0.008). The CT, TCA, SCA and choroidal HRF number significantly reduced after AL remission (p = 0.001, p = 0.047, p = 0.007 and p = 0.002 respectively). The CVI increased significantly compared to the active phase (p = 0.013). Conclusion: The study demonstrates a subclinical choroidal involvement in patients with AL, with relative stromal thickening in the acute phase, and normalization after disease remission. Choroidal HRF were identified as a biomarker of leukaemic choroidopathy. Choriocapillaris and choroidal vascularity were inversely correlated with a systemic pro‐coagulant state. [ABSTRACT FROM AUTHOR]

Purpose: Knowledge about oral health-related quality of life (OHRQoL) in adult patients with leukaemia is still limited. Accordingly, aim of this cross-sectional study was to assess OHRQoL and its associations to different parameters in adult patients with newly diagnosed acute leukaemia.Materials and Methods: Participants with first diagnosis of acute leukaemia were consecutively recruited in the Clinic of Hematology and Oncology of the University Medical Center Goettingen. OHRQoL was assessed using the German short form of oral health impact profile (OHIP-G14). Presence of oral initial symptoms, dental health (decayed- [D-T], missing- [M-T] and filled-teeth index [DMF-T]), dental behaviour and periodontal disease severity were assessed. For comparison, a healthy control group (HC) was recruited.Results: Thirty-nine patients with leukaemia and 38 HC were included. In the leukaemia group, a statistically significant and clinically relevant higher OHIP-sum score compared to HC was found (6.13 [3; 0-7] vs 0.87 [0; 0-2], p <0.01). The different subaspects of OHRQoL (patterns) 'oral function' and 'orofacial appearance' were statistically significantly worse in the leukaemia group (p <0.01). Time since diagnosis showed a clinically relevant association to the pattern 'psychosocial impact' (p = 0.06). Patients with oral initial symptoms had a statistically significantly worse OHIP-sum score (p <0.04, V = 0.775). DMF-T (p = 0.03, r = 0.242) and M-T (p = 0.03, r = 0.252) showed an association to OHIP sum score. Moreover, D-T (p = 0.03, r = 0.253) and M-T (p = 0.01, r = 0.296) were associated to orofacial appearance. Additionally, M-T showed an association to pattern 'oral function' (p = 0.01, r = 0.277).Conclusion: Patients with newly diagnosed acute leukaemia show a reduced OHRQoL. This might be particularly caused by oral health situation, especially oral initial symptoms as well as missing teeth. [ABSTRACT FROM AUTHOR]

Background Hyperleukocytosis is a high-mortality emergency that must be diagnosed and treated promptly. The treatment options are low-dose cytosine arabinoside, hydroxyurea, steroids and leukapheresis. The risks and benefits of leukapheresis and leukapheresis with cytoreductive drugs in hyperleukocytosis are unclear. Therefore, we aimed to evaluate the efficacy of leukapheresis and the effect of adding cytoreductive drugs to leukapheresis in reducing leukocyte count and mortality in our patients. Material and Methods Thirty-four adult patients with acute leukaemia who underwent leukapheresis were included in this retrospective study. Results The median age was 66.5 years old, and 88.2% of the patients were acute myeloid leukaemia. The total number of leukapheresis was 69 cycles, and the median number of the procedure was 2. The most common symptoms were associated with the pulmonary system (67.6%). The median follow-up was 17.5 days. The mean reduction of leukocyte count was 69,112/mm3, and the efficacy of leukapheresis was 40.9%. The decrease in leukocyte and platelet counts was statistically significant when compared before and after leukapheresis. The mortality rate was 76.5% during hospitalization. While 24 patients received concomitant cytoreductive drugs with leukapheresis, ten did not. There was no statistically significant difference between these groups regarding reducing leukocyte count, efficiency of leukapheresis and mortality (p values 0.857, 0.562 and 0.553). Conclusions In our study, we showed the efficacy of leukapheresis in hyperleukocytosis but failed to show any difference in leukocyte reduction or mortality with additional cytoreductive drugs. Leukapheresis with concomitant cytoreduction does not abolish or increase mortality. [ABSTRACT FROM AUTHOR]

Background: Published epidemiological studies of haematological cancers are few. Hereby we present a 20-year epidemiological data of haematological cancers in Sarawak from a population-based cancer registry. Methods: Haematological cancer cases with ICD-10 coded C81-C96 and ICD-O coded /3 diagnosed from 1996 to 2015 were retrieved from Sarawak Cancer Registry. Adult was defined as those 15 years and above. Incidence rate (IR) was calculated based on yearly Sarawak citizen population stratified to age, gender, and ethnic groups. Age-standardised IR (ASR) was calculated using Segi World Standard Population. Results: A total of 3,947 cases were retrieved and analysed. ASR was 10 and male predominance (IR ratio 1.32, 95%CI 1.24,1.41). Haematological cancers generally had a U-shaped distribution with lowest IR at age 10–14 years and exponential increment from age 40 years onwards, except acute lymphoblastic leukaemia (ALL) with highest IR in paediatric 2.8 versus adult 0.5. There was a significant difference in ethnic and specific categories of haematological cancers, of which, in general, Bidayuh (IR ratio 1.13, 95%CI 1.00, 1.27) and Melanau (IR ratio 0.54, 95%CI 0.45, 0.65) had the highest and lowest ethnic-specific IR, respectively, in comparison to Malay. The ASR (non-Hodgkin lymphoma, acute myeloid leukaemia, ALL, chronic myeloid leukaemia, and plasma cell neoplasm) showed a decreasing trend over the 20 years, -2.09 in general, while Hodgkin lymphoma showed an increasing trend of + 2.80. There was crude rate difference between the 11 administrative divisions of Sarawak. Conclusions: This study provided the IR and ASR of haematological cancers in Sarawak for comparison to other regions of the world. Ethnic diversity in Sarawak resulted in significant differences in IR and ASR. [ABSTRACT FROM AUTHOR]

Aiming to accommodate the unmet need for easily accessible biomarkers with a focus on biological differences between haematological diseases, the diagnostic value of plasma proteins in acute leukaemias and lymphomas was investigated. A multiplex proximity extension assay (PEA) was used to analyze 183 proteins in diagnostic plasma samples from 251 acute leukaemia and lymphoma patients and compared with samples from 60 healthy controls. Multivariate modelling using partial least square discriminant analysis revealed highly significant differences between distinct disease subgroups and controls. The model allowed explicit distinction between leukaemia and lymphoma, with few patients misclassified. Acute leukaemia samples had higher levels of proteins associated with haemostasis, inflammation, cell differentiation and cell-matrix integration, whereas lymphoma samples demonstrated higher levels of proteins known to be associated with tumour microenvironment and lymphoma dissemination. PEA technology can be used to screen for large number of plasma protein biomarkers in low µL sample volumes, enabling the distinction between controls, acute leukaemias and lymphomas. Plasma protein profiling could help gain insights into the pathophysiology of acute leukaemia and lymphoma and the technique may be a valuable tool in the diagnosis of these diseases. • PEA can discriminate between leukaemia and lymphoma. • Very few patients were misclassified. • Different protein profiles reflect different biological processes. • Processes identified in leukaemia: hemostasis, cell-differentiation and integration. • Processes identified in lymphoma: cell motility, matrix invasion and angiogenesis. [ABSTRACT FROM AUTHOR]

Down syndrome (DS) is the commonest chromosomal disorder and is considered to be the most common syndrome associated with acute leukaemia. The objective of this study was to determine the characteristics of acute leukaemia in children with DS in Pakistan. It was a retrospective, cohort study conducted over a 2-year period, and the data was analysed in SPSS 20.0 in terms of descriptive statistics. Nineteen DS patients with acute leukaemia were enrolled. The proportion of DS-acute leukaemia was found to be 1.84% among all cases of paediatric acute leukaemia. The mean age of presentation was 5.5 years ± 4.3 SD with a male to female ratio of 1.1:1. The precursor B-cell ALL was found in 13 (68.4%) and acute myeloid leukaemia was found in 6 (31.6%) patients of DS. Thirteen patients (68.4%) completed treatment, while 6 (31.6%) expired due to treatment-related toxicity. Mean overall survival was 38 months ± 5.34 SD. The status of diagnosis of DS before presentation with acute leukaemia was the only statistically significant factor associated with the outcome. Few distinct characteristics of DS-acute leukaemia have been found in our population. Treatment toxicity was the sole cause of treatment failure. [ABSTRACT FROM AUTHOR]

Introduction: Cytogenetic assessment is an essential test in patients with Acute Lymphoblastic Leukaemia (ALL), as it is required for diagnosis, treatment and to know the prognosis. Although these tests are done as standard of care in most of the institutes, there are limited publications from India describing karyotypic abnormalities in ALL patients. Aim: To assess the various cytogenetic abnormalities encountered in patients suffering from ALL and to know the pattern of chromosomal abnormalities. Materials and Methods: The present study was a retrospective cross-sectional study done at a tertiary care teaching hospital in Karnataka, India. Patients who were diagnosed with ALL based on flow cytometry between January 2017 and June 2021 were included in the present study and total 61 patients were evaluated for the cytogenetic findings. The medical records of these 61 patients were reviewed to collect their details like age, sex, immunophenotype and cytogenetic findings. Results: During flow cytometry analysis, side scatter vs CD45 expression strategy was applied. Events with low side scatter and dim CD45 expression (blast gate) were gated. Leukaemias expressing precursor markers (CD34/HLA-DR) along with cytoplasmic/surface CD3 were diagnosed as T-ALL. Leukaemias with precursor markers along with any two out of three B-cell markers i.e CD19, CD79a or CD10 were diagnosed as B-ALL. In this study 13 patients out of 35 had normal karyotype and this was the most common cytogenetic finding. The most common cytogenetic abnormality in B-ALL patients was hypodiploidy, but t(9;22) (q34;q11.2) was the most common cytogenetic abnormality in adult patients with B-ALL. Among the patients with T-ALL, only 2 (15.38%) patients had chromosomal abnormalities. Conclusion: The present study highlights the role of cytogenetics in patients undergoing treatment for ALL. Chromosomal abnormalities like t(9;12) (q13;p11.2), t(X;1) (q13;p36.1) and t(9;15) (p13;q11.2) are novel chromosomal abnormalities which were found in the present study. Long-term follow-up is necessary to identify prognostic implications of such chromosomal abnormalities. [ABSTRACT FROM AUTHOR]

Canine acute leukaemia is a heterogeneous neoplasm with multiple phenotypes. Criteria to subtype acute leukaemia by flow cytometry have not been validated. The goal of this study was to develop a panel of antibodies and objective antigen expression criteria for the assignment of lymphoid or myeloid lineage by flow cytometry. We isolated mRNA from the blood of 45 CD34+ acute leukaemia cases and measured expression of 43 genes that represent lymphoid and myeloid lineages using NanoString technology. We determined differentially expressed genes between major groups identified by unsupervised hierarchical clustering. We then evaluated the expression of antigens by flow cytometry to determine if cases could be assigned to a lineage. Two groups were identified by gene expression. Group 1/LYMPH overexpressed lymphoid‐associated genes (ex. DNTT) and had a higher percentage of CD5 + CD3‐ cells by flow cytometry. Group 2/MYELO overexpressed myeloid‐associated genes (ex. ANPEP/CD13) and had a higher percentage of class II major histocompatibility complex (MHCII)‐ CD14+ and/or CD18 + CD4‐ cells. We proposed that >12.5% CD5 + CD3‐ cells in the blood was indicative of lymphoid lineage, and > 3.0% CD14 + MHCII‐ cells or > 18% CD18 + MHCII‐CD4‐ cells was indicative of myeloid lineage. 15/15 cases that met the proposed criteria for acute lymphocytic leukaemia were in LYMPH group and 12/15 cases that met the proposed criteria for acute myeloid leukaemia were in MYELO group. The majority of CD34+ cases that did not meet either immunophenotyping lineage criterion (12/13) clustered within the LYMPH group. In conclusion, currently available antibodies can be useful for determining canine acute leukaemia subtypes. [ABSTRACT FROM AUTHOR]

It is essential to relate the biology of acute leukaemia to normal blood cell development. In this review, we discuss how modern models of haematopoiesis might inform approaches to diagnosis and management of immature leukaemias, with a specific focus on T‐lymphoid and myeloid cases. In particular, we consider whether next‐generation analytical tools could provide new perspectives that could improve our understanding of immature blood cancer biology. [ABSTRACT FROM AUTHOR]

Summary: The standardized EuroFlow protocol, including CD19 as primary B‐cell marker, enables highly sensitive and reliable minimal residual disease (MRD) assessment in B‐cell precursor acute lymphoblastic leukaemia (BCP‐ALL) patients treated with chemotherapy. We developed and validated an alternative gating strategy allowing reliable MRD analysis in BCP‐ALL patients treated with CD19‐targeting therapies. Concordant data were obtained in 92% of targeted therapy patients who remained CD19‐positive, whereas this was 81% in patients that became (partially) CD19‐negative. Nevertheless, in both groups median MRD values showed excellent correlation with the original MRD data, indicating that, despite higher interlaboratory variation, the overall MRD analysis was correct. [ABSTRACT FROM AUTHOR]

Summary: Rearrangements of Janus kinase 2 (JAK2r) form a subtype of acute lymphoblastic leukaemia (ALL) associated with poor patient outcomes. We present a high‐risk case of B‐cell ALL (B‐ALL) where retrospective mRNA sequencing identified a novel GOLGA4–JAK2 fusion gene. Expression of GOLGA4–JAK2 in murine pro‐B cells promoted factor‐independent growth, implicating GOLGA4–JAK2 as an oncogenic driver. Cells expressing GOLGA4–JAK2 demonstrated constitutive activation of JAK/STAT signalling and were sensitive to JAK inhibitors. This study contributes to the diverse collection of JAK2 fusion genes identified in B‐ALL and supports the incorporation of JAK inhibitors into treatment strategies to improve outcomes for this subtype. [ABSTRACT FROM AUTHOR]

Acute leukemia (AL) occurring in pregnancy is extremely rare, and its treatment is a clinical dilemma. We retrospectively reviewed the medical records of our hospital from 2010 to 2019. Twenty-one patients were diagnosed with AL during pregnancy. Of whom, eighteen had acute myeloid leukemia, and 3 had acute lymphoblastic leukemia. Six, eight and seven patients were diagnosed during the first, second, and third trimester, respectively. Six of the 21 patients experienced therapeutic abortion and 1 had spontaneous abortion, whereas 9 gave birth to healthy babies (4 through vaginal deliveries and 5 with Caesarean sections). Four babies had been exposed to chemotherapeutic agents, but no congenital malformations were observed. Sixteen patients received chemotherapy, while 4 patients died before chemotherapy and one was discharged after refusing chemotherapy. The complete remission rate of the 10 patients who began chemotherapy immediately after diagnosis was 80%, compared with 66.7% in the 6 patients who started chemotherapy after abortion or delivery. Three remain alive. In general, initiation of chemotherapy as early as possible may increase the CR rate. Combined with literature data, we proposed that, for patients diagnosed in early and late stages of pregnancy (>30 weeks), elective termination or induced delivery before chemotherapy may be a good choice for better maternal (and fetal) outcome. Acute leukaemia diagnosed in pregnancy is extremely rare, and its treatment is a clinical dilemma. In general, initiation of chemotherapy as early as possible may increase the CR rate. For patients who are diagnosed in the first trimester or late stage of pregnancy (>30 weeks), elective termination or induced delivery before starting chemotherapy may be a good choice for better maternal (and fetal) outcome. [ABSTRACT FROM AUTHOR]

Aims: This open‐label, phase I study evaluated the pharmacokinetics and safety of pegylated recombinant human granulocyte colony‐stimulating factor (PEG‐rhG‐CSF) for the treatment of chemotherapy‐induced neutropenia in children with acute leukaemia. Methods: PEG‐rhG‐CSF was administered as a single 100 mcg/kg (3 mg maximum dose) subcutaneous injection at the end of each chemotherapy period when neutropenia occurred. Blood samples were obtained from patients treated with PEG‐rhG‐CSF. PEG‐rhG‐CSF serum concentrations were determined by an enzyme‐linked immunosorbent assay. Population pharmacokinetic (PPK) analysis was implemented using the nonlinear mixed‐effects model. Short‐term safety was evaluated through adverse events collection (registered at clinicaltrials.gov identifier: 03844360). Results: A total of 16 acute leukaemia patients (1.8–13.6 years) were included, of whom two (12.5%) had grade 3 neutropenia, six (37.5%) had grade 4 neutropenia, and eight (50.0%) had severe neutropenia. For PPK modelling, 64 PEG‐rhG‐CSF serum concentrations were obtainable. A one‐compartment model with first‐order elimination was used for pharmacokinetic data modelling. The current weight was a significant covariate. The median (range) of clearance (CL) and area under the serum concentration–time curve (AUC) were 5.65 (1.49–14.45) mL/h/kg and 16514.75 (6632.45–54423.30) ng·h/mL, respectively. Bone pain, pyrexia, anaphylaxis and nephrotoxicity were not observed. One patient died 13 days after administration, and the objective assessment of causality was that an association with PEG‐rhG‐CSF was "possible". Conclusions: The AUC of PEG‐rhG‐CSF (100 mcg/kg, 3 mg maximum dose) in paediatric patients with acute leukaemia were similar to those of PEG‐rhG‐CSF (100 mcg/kg) in children with sarcoma. PEG‐rhG‐CSF is safe, representing an important therapeutic option for chemotherapy‐induced neutropenia in paediatric patients with acute leukaemia. [ABSTRACT FROM AUTHOR]

Summary: Older patients with acute myeloid leukaemia (AML) account for nearly half of those with the disease. Because they are perceived to be unfit for, unwilling to receive, or unlikely to benefit from conventional chemotherapy they represent an important unmet need. Tosedostat is a selective oral aminopeptidase inhibitor, which in phase I/II trials showed acceptable toxicity and encouraging efficacy. We report the only randomised study of low‐dose cytosine arabinoside (LDAC) combined with tosedostat (LDAC‐T) versus LDAC in untreated older patients not suitable for intensive treatment. A total of 243 patients were randomised 1:1 as part of the 'Pick‐a‐Winner' LI‐1 trial. There was a statistically non‐significant increase in the complete remission (CR) rate with the addition of tosedostat, LDAC‐T 19% versus LDAC 12% [odds ratio (OR) 0·61, 95% confidence interval (CI) 0·30–1·23; P = 0·17]. For overall response (CR+CR with incomplete recovery of counts), there was little evidence of a benefit to the addition of tosedostat (25% vs. 18%; OR 0·68, 95% CI 0·37–1·27; P = 0·22). However, overall survival (OS) showed no difference (2‐year OS 16% vs. 12%, hazard ratio 0·97, 95% CI 0·73–1·28; P = 0·8). Exploratory analyses failed to identify any subgroup benefitting from tosedostat. Despite promising pre‐clinical, early non‐randomised clinical data with acceptable toxicity and an improvement in response, we did not find evidence that the addition of tosedostat to LDAC produced a survival benefit in this group of patients with AML. International Standard Randomised Controlled Trial Number: ISRCTN40571019 [ABSTRACT FROM AUTHOR]

Summary: Given its myeloid‐restricted expression, myeloperoxidase (MPO) is typically used for lineage assignment (myeloid vs. lymphoid) during acute leukaemia (AL) diagnostics. In the present study, a robust flow cytometric definition for MPO positivity was established based on the standardised EuroFlow protocols, the standardised Acute Leukaemia Orientation Tube and 1734 multicentre AL cases (with confirmed assay stability). The best diagnostic performance was achieved by defining MPO positivity as ≥20% of the AL cells exceeding a lymphocyte‐based threshold. The methodology employed should be applicable to any form of standardised flow cytometry. [ABSTRACT FROM AUTHOR]

Introduction: Acute leukemia (AL) occurring in pregnancy is extremely rare, and its treatment is a clinical dilemma. Methods: We retrospectively reviewed the medical records of our hospital from 2010 to 2019. Results: Twenty-one patients were diagnosed with AL during pregnancy. Of whom, eighteen had acute myeloid leukemia, and 3 had acute lymphoblastic leukemia. Six, eight and seven patients were diagnosed during the first, second, and third trimester, respectively. Six of the 21 patients experienced therapeutic abortion and 1 had spontaneous abortion, whereas 9 gave birth to healthy babies (4 through vaginal deliveries and 5 with Caesarean sections). Four babies had been exposed to chemotherapeutic agents, but no congenital malformations were observed. Sixteen patients received chemotherapy, while 4 patients died before chemotherapy and one was discharged after refusing chemotherapy. The complete remission rate of the 10 patients who began chemotherapy immediately after diagnosis was 80%, compared with 66.7% in the 6 patients who started chemotherapy after abortion or delivery. Three remain alive. Conclusions: In general, initiation of chemotherapy as early as possible may increase the CR rate. Combined with literature data, we proposed that, for patients diagnosed in early and late stages of pregnancy (>30 weeks), elective termination or induced delivery before chemotherapy may be a good choice for better maternal (and fetal) outcome. [ABSTRACT FROM AUTHOR]

Interleukin-1 blockade with anakinra in acute leukaemia patients with severe COVID-19 pneumonia appears safe and may result in clinical improvement Keywords: haemophagocytic syndrome; acute leukaemia; infection; immunotherapy EN haemophagocytic syndrome acute leukaemia infection immunotherapy e80 e83 4 07/20/20 20200715 NES 200715 As of 17 May 2020 the number of patients infected by coronavirus disease 2019 (COVID-19) worldwide has exceeded 4-5 million.1 A subgroup of patients with COVID-19 pneumonia develop a hyperinflammatory syndrome which has a similar cytokine release profile to secondary haemophagocytic lymphohistiocytosis (HLH).2 Immunomodulatory drugs are hypothesised to abrogate the dysfunctional immune response in hyperinflammatory COVID-19 and are currently being investigated in clinical trials. In this report we demonstrate that anakinra is safe in haematology patients and resulted in a clinical improvement in three patients with acute leukaemia and confirmed or suspected COVID-19 pneumonia with a life-threatening hyper-inflammatory syndrome. [Extracted from the article]

Background and Objectives: Haematological malignancies account for approximately 40% of all cancers by the age of 15 years. Acute leukaemia (AL) account for one-third of childhood cancer cases; consisting of Acute Lymphoblastic Leukaemia (ALL) and Acute Myeloid Leukaemia (AML). The aim of this work is to describe the epidemiological, clinical, biological and evolutionary characteristics of children with acute leukaemia in the western and south-western region of Algeria. Patients and Methods: A three-year retrospective study was undergone from January 2016 to December 2018 on children with acute leukaemia. The study was conducted at the paediatric oncology department of the anti-cancer -Emir AEK- of Missreghine in Oran. Results: During this period, we identified 135 cases of diagnosed AL. The sex ratio M/F was 1.1. The "two to five -year" age group was the most affected. The prevalence of ALL, AML, and biphenotypic acute leukaemia (BAL) was 60.45%, 23.88%, and 15.57%, respectively. The clinical signs were mainly presented by the tumour syndrome dominated by the presence of lymphadenopathy (63%) and splenomegaly (56.3%). The most frequent abnormal blood abnormalities were anaemia (66.66% in ALL and 28.14% in AML), thrombocytopenia (75.9% in ALL and 24.4% in AML) and leukocytosis (76.3% ALL and 23.7% AML). Conclusion: Paediatric acute leukaemia is a real public health problem that requires special care and attention. This management must involve all epidemiological, clinical and biological aspects for this highly sensitive age group. [ABSTRACT FROM AUTHOR]

Background: Patients with acute leukaemia (AL) usually require prolonged periods of hospitalisation. The treatment and clinical symptoms may lead to patients' supportive care needs (SCNs) not being met and impairs their quality of life (QoL). Studies on QoL and SCNs among AL patients are limited. This study aimed to identify the unmet SCNs and its relation to QoL of adult AL patients in China.Methods: This multicentre cross-sectional study recruited 346 participants to complete a self-developed questionnaire, detailing demographic information and disease-related variables. A 34-item Supportive Care Needs Survey (SCNS-SF34) was used to identify unmet SCNs, and the Functional Assessment of Cancer Therapy-Leukaemia (FACT-Leu) questionnaire measured patients' QoL.Results: Unmet SCN rates for the 34 items ranged from17.6 to 81.7%. Patients' needs were high for health systems and information, but low in the sexual domain. The results reveal nine factors associated with the unmet SCNs of adult AL patients, including marital status, original residence, age, education, occupation, other diseases, chemotherapy course, disease course, and treatment stage (p < 0.05). The total score of the FACT-Leu negatively correlated with the SCNS-SF34 in the physical/daily living (r = - 0.527, p < 0.01), psychological (r = - 0.688, p < 0.01), sexual (r = - 0.170, p < 0.01), patient care and support (r = - 0.352, p < 0.01), and health systems and information (r = - 0.220, p < 0.01) domains.Conclusions: Adult AL patients exhibit a high demand for unmet SCNs, especially in the domain of health systems and information. There was a significant association between patients' unmet SCNs and QoL. Future research should develop tailored interventions to address the unmet SCNs of adult AL patients, to further improve their QoL. [ABSTRACT FROM AUTHOR]

Summary: Acute myeloid leukaemia (AML) is rarely reported in horses and myelodysplastic syndrome (MDS) has been described only in one case. Acute myeloid leukaemia is defined as the presence of at least 20% blasts in the marrow or blood. On the other hand, MDS is characterised by morphologic abnormalities in one or more cell lineages with hypercellular marrow and peripheral cytopenias due to ineffective haematopoiesis. We report a case of acute myelomonocytic leukaemia with myelodysplasia‐related features in a horse. A supposed diagnosis was based on abnormal morphology of circulating neoplastic cells and bone marrow cytology. A final diagnosis was made by using flow cytometry (FC) in conjunction with cytochemistry (CC) rarely reported in the haematopoietic neoplasms of the horse. [ABSTRACT FROM AUTHOR]

Context Acute leukaemia diagnosis is a field requiring automated solutions, tools and methods and the ability to facilitate early detection and even prediction. Many studies have focused on the automatic detection and classification of acute leukaemia and their subtypes to promote enable highly accurate diagnosis. Objective This study aimed to review and analyse literature related to the detection and classification of acute leukaemia. The factors that were considered to improve understanding on the field's various contextual aspects in published studies and characteristics were motivation, open challenges that confronted researchers and recommendations presented to researchers to enhance this vital research area. Methods We systematically searched all articles about the classification and detection of acute leukaemia, as well as their evaluation and benchmarking, in three main databases: ScienceDirect, Web of Science and IEEE Xplore from 2007 to 2017. These indices were considered to be sufficiently extensive to encompass our field of literature. Results Based on our inclusion and exclusion criteria, 89 articles were selected. Most studies (58/89) focused on the methods or algorithms of acute leukaemia classification, a number of papers (22/89) covered the developed systems for the detection or diagnosis of acute leukaemia and few papers (5/89) presented evaluation and comparative studies. The smallest portion (4/89) of articles comprised reviews and surveys. Discussion Acute leukaemia diagnosis, which is a field requiring automated solutions, tools and methods, entails the ability to facilitate early detection or even prediction. Many studies have been performed on the automatic detection and classification of acute leukaemia and their subtypes to promote accurate diagnosis. Conclusions Research areas on medical-image classification vary, but they are all equally vital. We expect this systematic review to help emphasise current research opportunities and thus extend and create additional research fields. [ABSTRACT FROM AUTHOR]

Advances in the classification of acute leukaemias have led to improved outcomes for a substantial fraction of patients. However, chemotherapy resistance remains a major problem for specific subsets of acute leukaemias. Here, we propose that a molecularly distinct subtype of acute leukaemia with shared myeloid and T cell lymphoblastic features, which we term acute myeloid/T-lymphoblastic leukaemia (AMTL), is divided across 3 diagnostic categories owing to variable expression of markers deemed to be defining of myeloid and T-lymphoid lineages, such as myeloperoxidase and CD3. This proposed diagnostic group is supported by (i) retained myeloid differentiation potential during early T cell lymphoid development, (ii) recognition that some cases of acute myeloid leukaemia (AML) harbour hallmarks of T cell development, such as T-cell receptor gene rearrangements and (iii) common gene mutations in subsets of AML and T cell acute lymphoblastic leukaemia (T-ALL), including WT1, PHF6, RUNX1 and BCL11B. This proposed diagnostic entity overlaps with early T cell precursor (ETP) T-ALL and T cell/myeloid mixed phenotype acute leukaemias (MPALs), and also includes a subset of leukaemias currently classified as AML with features of T-lymphoblastic development. The proposed classification of AMTL as a distinct entity would enable more precise prospective diagnosis and permit the development of improved therapies for patients whose treatment is inadequate with current approaches. [ABSTRACT FROM AUTHOR]

Objective: To determine the frequency of clinical presentation of newly diagnosed 50 patients of acute leukaemia. Material & Methods: This study was conducted at Department of Paediatrics, Khyber Teaching Hospital, Peshawar, Pakistan from March 2016 to September 2017. A cross-sectional descriptive study design was used and 50 patients presenting with fever, pallor, organomegaly and diagnostic evidence of newly diagnosed acute leukaemia were elected through non randomised convenient sampling. Common clinical features were noted along with hematological parameters. The cases were then managed according to standardized management criteria. Results: Pallor (80%) fever high grade (78%) splenomegaly (62%) were the most common clinical features. Bone marrow examination showed total 46 (92%) patients of ALL and 4 (8%) patients of AML. Conclusion: In our study we found out that acute lymphoblastic leukaemia was the most common type of leukaemia comprising of 46 (92%) patients and 4 (8%) patients were acute myelogenous leukaemia. Fever and Pallor are the commonest clinical findings of acute leukaemia. Bone marrow examination is mandatory for the diagnosis because delay in the diagnosis will adversely affect the management. [ABSTRACT FROM AUTHOR]

Relapse is the main cause of treatment failure after allogeneic haematopoietic stem cell transplantation (allo- HSCT) for acute leukaemia ( AL). Post-transplantation minimal residual disease ( MRD) monitoring enables risk stratification and identifies AL patients at higher risk of relapse. MRD assessment primarily involves the determination of leukaemia-associated immunophenotypic patterns using multiparameter flow cytometry, and the polymerase chain reaction ( PCR)-based evaluation of expression levels of leukaemia-related genes (specific reciprocal gene rearrangements and other mutation types). In addition, next generation sequencing and digital PCR may further enrich current MRD detection. Several MRD-directed interventions have demonstrated the ability to reduce the risk of relapse with acceptable treatment-related toxicities. Donor lymphocyte infusion ( DLI) is the most important intervention for MRD-positive patients, while several modified strategies, such as granulocyte colony-stimulating factor-mobilized peripheral blood cells followed by short term immune suppression and escalating dose regimen, further improve the safety and efficacy of DLI. Interferon therapy, targeted drugs, and hypomethylating agents have also been introduced for MRD-directed interventions. Referring to the issues of whether and who would benefit from pre-emptive intervention according to MRD, in this review, we summarized this rapidly evolving area of MRD monitoring and MRD-directed interventions in AL patients after allo- HSCT. [ABSTRACT FROM AUTHOR]

Acute leukaemia ( AL) is a bone marrow malignancy of hematopoietic progenitors that historically is poorly responsive to treatment. With the widespread adoption of dose-intense chemotherapy, more human patients attain long-term survivals, but whether comparable progress has been made in canine AL is unknown. To investigate this question, medical records from three academic veterinary hospitals were reviewed. Fifty dogs met the criteria for AL, having excess circulating or marrow blasts, a major cytopenia(s), and no substantial lymphadenopathy. Thirty-six dogs received cytotoxic chemotherapy; 23 achieved a complete or partial response for a median of 56 days (range, 9-218). With failure or relapse, 14 dogs were rescued. Median survival with treatment was poor at 55 days (range, 1-300). Untreated ( n = 6) and palliatively-treated ( n = 8) dogs lived a median of 7.5 days. Most dogs developed chemoresistance within weeks of initiating treatment, and consequently, survival times for AL remain disappointingly short. [ABSTRACT FROM AUTHOR]

acute leukaemias are a heterogeneous group of clonal neoplastic nature with undifferentiated stem cells, or partially differentiated, characterized by stopping differentiation and maturation of these cells, associated or not with their passage in the peripheral blood. The disease has a high incidence, affecting all age groups. Investigate automatic CBC gives extremely precise and clear indications of the presence of a number of cells outside the limits of variation or of the presence of a distribution or abnormal morphology. Comparing the data obtained from processing CBC from patients investigated with biological reference values from literature the authors have found that leukocytes reached a value six times higher (602 %) than the maximum reference value;these values were associated with thrombocytopenia and hypochromia.In all evaluated patients, CBC signalled the presence of blasts and undifferentiated cells that motivate further investigation. [ABSTRACT FROM AUTHOR]

capturing and highlighting morphological changes that occur in the examination of a peripheral blood smear or bone marrow are important in the diagnosis of acute leukaemia, motivating the goal of this paper. The examination of blood smears from all patients included in the study revealed the presence of blast cells (2-97% of total leukocyte cell line). Of total studied smears, most presented type I and II blasts, which pointed to acute lymphoblastic leukaemia (LAM) 2, 3, 4 and 5; lymphoblastic modest presence pointed to acute lymphoblastic leukaemia (LAL) (4%). About 36% of smears of blood blast cells analyzed showed a pronounced polymorphism, which could not be classified even after performing bone marrow aspirate, requiring further investigation to establish the diagnosis. [ABSTRACT FROM AUTHOR]

Few studies have evaluated the impact of complications, sociodemographic and clinical factors on early mortality (death ≤60 days from diagnosis) in acute myeloid leukaemia (AML) patients. Using data from the California Cancer Registry linked to hospital discharge records from 1999 to 2012, we identified patients aged ≥15 years with AML who received inpatient treatment ( N = 6359). Multivariate logistic regression analyses were used to assess the association of complications with early mortality, adjusting for sociodemographic factors, comorbidities and hospital type. Early mortality decreased over time (25·3%, 1999-2000; 16·8%, 2011-2012) across all age groups, but was higher in older patients (6·9%, 15-39, 11·4%, 40-54, 18·6% 55-65, and 35·8%, >65 years). Major bleeding [Odds ratio ( OR) 1·5, 95% confidence interval ( CI) 1·3-1·9], liver failure ( OR 1·9, 95% CI 1·1-3·1), renal failure ( OR 2·4, 95% CI 2·0-2·9), respiratory failure ( OR 7·6, 95% CI 6·2-9·3) and cardiac arrest ( OR 15·8, 95% CI 8·7-28·6) were associated with early mortality. Higher early mortality was also associated with single marital status, low neighbourhood socioeconomic status, lack of health insurance and comorbidities. Treatment at National Cancer Institute-designated cancer centres was associated with lower early mortality ( OR 0·5, 95% CI 0·4-0·6). In conclusion, organ dysfunction, hospital type and sociodemographic factors impact early mortality. Further studies should investigate how differences in healthcare delivery affect early mortality. [ABSTRACT FROM AUTHOR]

Invasive fungal infections (IFI) remain life-threatening complications in haematological patients. The aim of the study was to present the experience of a single centre in the surgical treatment of pulmonary IFI. Between 1992 and 2014, 50 haematological patients with IFI underwent pulmonary resection. In 27 cases it was an emergency procedure to avoid haemoptysis (if the lesion threatened pulmonary vessels). The remaining 23 patients underwent elective surgery before new chemotherapy or stem-cell transplantation. Among these patients (median age: 54 years; range: 5–70 years), 92% had acute leukaemia and 68% were on haematological first-line therapy (receiving induction or consolidation chemotherapies). Invasive pulmonary aspergillosis and pulmonary mucormycosis were diagnosed in 37 and 12 patients, respectively. One patient had IFI due to Trichoderma longibrachiatum . All of the patients received antifungal agents. In the month preceding IFI diagnosis, 94% of patients had been neutropenic. At the time of surgery, 30% of patients were still neutropenic and 54% required platelet transfusions. Lobectomy or segmentectomy were performed in 80% and 20% of cases, respectively. Mortality at 30 and 90 days post-surgery was 6% and 10%, respectively. After surgery, median overall survival was 21 months; median overall survival was similar between patients with emergency or elective surgery and between the types of IFI (invasive pulmonary aspergillosis or pulmonary mucormycosis). However, overall survival was far better in haematological first-line patients or in those achieving a haematological complete response than in other patients (p <0.001). In pulmonary IFI, lung resection could be an effective complement to medical treatment in selected haematological patients. [ABSTRACT FROM AUTHOR]