The latest medical research on Acute Lymphoblastic Leukaemia

The research magnet gathers the latest research from around the web, based on your specialty area. Below you will find a sample of some of the most recent articles from reputable medical journals about acute lymphoblastic leukaemia gathered by our medical AI research bot.

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Post thrombotic syndrome after upper extremity deep vein thrombosis; An international Delphi consensus study.

Acute Lymphoblastic Leukaemia

Primary deep venous thrombosis of the upper extremity (UEDVT) is a rare condition but up to 60% of patients may develop post thrombotic syndrome in the upper extremity (UE-PTS) with significant morbidity and decreased quality of life. However, there is no universally accepted method to diagnose and classify UE-PTS, hampering scientific research on UEDVT treatment. Through this international Delphi consensus study we aimed to determine what a clinical score for diagnosing UE-PTS should entail.

An online focus group survey among 20 patients treated for UEDVT was performed to provide clinical parameters before the start of a four round electronic Delphi consensus study among 25 international experts. The CREDES recommendations on Conducting and Reporting Delphi Studies were applied. Open text questions, multiple selection questions and 9-point Likert scales were used. Consensus was set at 70% agreement.

After four rounds, agreement was reached on a composite score of five symptoms and three clinical signs, combined with a functional disability score. The signs and symptom will each be scored on a severity scale of 0-3 and the total score expressed as an ordinal variable; no /mild /moderate /or severe PTS. The functional disability portion measures the impact of the signs and symptoms on the functionality of the patients arm.

Consensus was reached on a composite score of signs and symptoms of UE-PTS combined with a functional disability score. Clinical validation of the UE-PTS score in a large patient cohort is mandatory to facilitate application in future research.

Anti-PF4 testing for Vaccine-induced Immune Thrombocytopenia and Thrombosis (VITT). Results from a NEQAS, ECAT and SSC collaborative exercise in 385 centres worldwide.

Acute Lymphoblastic Leukaemia

Vaccine-induced immune thrombocytopenia and thrombosis (VITT) following the administration of the AstraZeneca (AZ) ChAdOx1 nCOV-19 vaccine is a well-recognised clinical phenomenon. The associated clinical and laboratory features have included thrombosis at unusual sites, thrombocytopenia, raised D-Dimer levels and positivity for immunoglobulin G (IgG) anti-platelet factor 4 (PF4) antibodies.

A collaborative external quality assessment (EQA) exercise was carried out by distributing 5 lyophilised samples from subjects with VITT and one from a healthy subject to 500 centres performing Heparin Induced Thrombocytopenia (HIT) testing.

Participating centres employed their locally validated testing methods for HIT assays, with some participants additionally reporting results for VITT modified assays.

A total of 385 centres returned results for: anti-PF4 immunoassay and functional assays. The ELISA assays used in the detection of anti-PF4 antibodies for the samples distributed had superior sensitivities compared to both the functional assays and the non-ELISA methods.

ELISA based methods to detect anti PF4 antibodies have a greater sensitivity in confirmation of VITT when compared to functional assays regardless of whether such functional assays were modified to be specific for VITT. Rapid immunoassays should not be employed to detect VITT antibodies.

Risk of SARS-CoV-2 Breakthrough Infection in Vaccinated Cancer Patients: A Retrospective Cohort Study.

Leukaemia

Although messenger RNA (mRNA) vaccines have established efficacy for prevention of severe SARS-CoV2 infection in the general population, their effe...

Direct oral anticoagulant versus low molecular weight heparin for the treatment of cancer-associated venous thromboembolism: 2022 updated systematic review and meta-analysis of randomized controlled trials.

Leukaemia

International clinical practice guidelines have progressively endorsed direct oral anticoagulants (DOACs) as an alternative to low-molecular-weight...

The p.P1127S pathogenic variant lowers von Willebrand factor levels through higher affinity for the macrophagic scavenger receptor LRP1: clinical phenotype and pathogenic mechanisms.

Acute Lymphoblastic Leukaemia

The index case is a 21-year-old Italian woman with a mild haemorrhagic syndrome and VWF:Ag=34.3 U/dL, VWF:GpIbR=32.8 U/dL and FVIII=55.3 IU/dL.

The aim of this study is to characterize from a genetic and biochemical standpoint this low VWF phenotype.

Coagulation and biochemical methods were used to study the structural and functional pattern of VWF multimers in the index case's plasma. Recombinant WT and p.P1127S VWF variants were produced using HEK-293 cells. In addition, genetic screening was carried out to detect SNVs of some scavenger VWF/FVIII receptors gene such as CLEC4M, STAB2 and ASGR2.

Genetic investigation revealed that the index case inherited from her mother the heterozygous missense mutation c.3379C>T (VWF exon 25), causing the p.P1127S substitution in the VWF D'D3 domain. The index case was also homozygous for the scavenger receptor ASGR2 c.-95 CC-genotype. Desmopressin normalized the VWF level of the patient, although its clearance was faster (t1/2 =6.7 h) than in normal subjects (t1/2 =12±0.7 h). FVIII-VWF interaction, ADAMTS-13 levels, ristocetin-induced-platelet-aggregation, and VWF multimeric pattern were normal. The p.P1127S variant was normally synthesized and secreted by HEK-293 cells, and molecular modeling predicts a conformational changeshowing higher affinity for the macrophagic scavenger receptor LRP1, as also experimentally verified.

The p.P1127S variant may cause a low VWF phenotype, stemming from an increased VWF affinity for the scavenger receptor LRP1 and, consequently, an accelerated clearance of VWF.

Importance of Catecholamine Signaling in the Development of Platelet Exhaustion after Traumatic Injury.

Acute Lymphoblastic Leukaemia

Impaired ex-vivo platelet aggregation is common in trauma patients. The mechanisms driving these impairments remains incompletely understood, but functional platelet exhaustion due excessive in-vivo activation is implicated. Given platelet adrenoreceptors and known catecholamine surges after injury, impaired ex-vivo platelet aggregation in trauma patients may be linked to catecholamine induced functional platelet exhaustion.

To determine the relationship of catecholamines with platelet-dependent hemostasis after injury and to model catecholamine induced functional platelet exhaustion in healthy donor platelets.

Whole blood was collected from 67 trauma patients as part of a prospective cohort study. Platelet aggregometry and rotational thromboelastometry were performed, and plasma epinephrine (EPI) and norepinephrine (NE) concentrations were measured. The effect of catecholamines on healthy donor platelets was examined in a microfluidic model, with platelet aggregometry, and by flow cytometry examining surface markers of platelet activation.

In trauma patients, EPI and NE were associated with impaired platelet aggregation (both p<0.05), and EPI was additionally associated with decreased viscoelastic clot strength, increased fibrinolysis, and mortality (all p<0.05). In healthy donors, short duration incubation with EPI enhanced platelet aggregation, platelet adhesion under flow, and increased glycoprotein IIb/IIIa activation, while weaker effects were observed with NE. Compared to short incubation, longer incubation with EPI resulted in decreased platelet adhesion, platelet aggregation, and surface expression of glycoprotein IIb/IIIa.

These findings suggest sympathoadrenal activation in trauma patients contributes to impaired ex-vivo platelet aggregation, which mechanistically may be explained by a functionally exhausted platelet phenotype under prolonged exposure to high plasma catecholamine levels.

Worked to the bone: antibody-based conditioning as the future of transplant biology.

Leukaemia

Conditioning of the bone marrow prior to haematopoietic stem cell transplant is essential in eradicating the primary cause of disease, facilitating...

Step down to six months of prophylactic-dose low-molecular-weight heparin after initial full-dose anticoagulation for the treatment of cancer-associated thrombosis (STEP-CAT): a pilot study.

Acute Lymphoblastic Leukaemia

Patients with cancer-associated thrombosis (CAT) are treated with full-dose anticoagulation for at least three months, but optimal dosing thereafter is unknown.

We explored the feasibility of extended prophylactic-dose low-molecular-weight heparin (LMWH) treatment following a minimum of three months of full-dose LMWH.

We conducted a multicenter prospective pilot study of patients with CAT who completed at least three months of therapeutic-dose LMWH. Patients received six months of prophylactic-dose subcutaneous enoxaparin (40 mg once daily). The primary outcome was recurrence of deep vein thrombosis (DVT) or pulmonary embolism (PE), and secondary outcomes included major, clinically relevant non-major (CRNM), and minor bleeding.

From August 2016 to May 2019, 52 patients with a mean age of 64.1 years were included. The study was stopped early due to poor recruitment. Breast (23.1%) and colorectal (19.2%) were the most common cancers, and 61.0% had stage IV malignancy. Index CAT consisted of deep vein thrombosis (DVT) alone in 57.7% of patients and pulmonary embolism (PE) with or without DVT in 42.3%. Patients received a mean of 7.6 months of weight-adjusted LMWH prior to enrollment. During a mean follow-up of 5.6 months, 1 patient was diagnosed with recurrent incidental PE (0.0035 events/subject-month). There were no major bleeding events, 1 CRNM, and 1 minor bleeding event. Eight (15.4%) patients died; 6 due to cancer and 2 due to respiratory disease unrelated to PE.

These results, in part, provide support for trials of extended reduced-dose anticoagulation for the secondary prevention of CAT. (ClinicalTrials.gov: NCT02752607.).

Life without blood: Molecular and functional analysis of hirudins and hirudin-like factors of the Asian non-hematophagous leech Whitmania pigra.

Acute Lymphoblastic Leukaemia

Several leech species of the genera Hirudo, Hirudinaria and Whitmania are widely used in Traditional Chinese Medicine for the oral treatment of disorders associated with blood stasis. Among them, the non-hematophagous leech Whitmania pigra expresses a variety of components that have the potential to act on the vertebrate blood coagulation system.

Whether or not the thrombin inhibitor hirudin, probably the most prominent leech-derived anticoagulant, is actually present in Whitmania pigra, is still a matter of debate. To answer that open question was the ultimate aim of the study.

We identified several putative hirudin-encoding sequences in transcriptome data of Whitmania pigra. Upon gene synthesis and molecular cloning the respective recombinant proteins were expressed in Escherichia coli, purified, processed and eventually functionally characterized for thrombin-inhibitory potencies in coagulation assays.

We were successful in the identification and functional characterization of several putative hirudins in Whitmania pigra. Some, but not all of these factors are indeed thrombin inhibitors. Whitmania pigra hence expresses both hirudins (factors that inhibit thrombin) and hirudin-like factors (that do not or only very weakly inhibit thrombin). Furthermore we revealed the exon/intron-structures of the corresponding genes. Coding sequences of some putative hirudins of Whitmania pigra were present also in transcriptome datasets of Hirudo nipponia, a hematophagous leech that is likewise used in TCM.

Based on both structural and functional data we provide very strong evidence for the expression of hirudins in Whitmania pigra. This is the first description of hirudins in a non-hematophagous leech.

Immunosuppressive cells in cancer: mechanisms and potential therapeutic targets.

Leukaemia

Immunotherapies like the adoptive transfer of gene-engineered T cells and immune checkpoint inhibitors are novel therapeutic modalities for advance...

Homologous recombination deficiency (HRD) can predict the therapeutic outcomes of immuno-neoadjuvant therapy in NSCLC patients.

Leukaemia

Neoadjuvant immunotherapy is emerging as novel effective intervention in lung cancer, but study to unearth effective surrogates indicating its therapeutic outcomes is limited. We investigated the genetic changes between non-small cell lung cancer (NSCLC) patients with varied response to neoadjuvant immunotherapy and discovered highly potential biomarkers with indicative capability in predicting outcomes.

In this study, 3 adenocarcinoma and 11 squamous cell carcinoma NSCLC patients were treated by neoadjuvant immunotherapy with variated regimens followed by surgical resection. Treatment-naive FFPE or fresh tissues and blood samples were subjected to whole-exome sequencing (WES). Genetic alternations were compared between differently-responded patients. Findings were further validated in multiple public cohorts.

DNA damage repair (DDR)-related InDel signatures and DDR-related gene mutations were enriched in better-responded patients, i.e., major pathological response (MPR) group. Besides, MPR patients exhibited provoked genome instability and unique homologous recombination deficiency (HRD) events. By further inspecting alternation status of homology-dependent recombination (HR) pathway genes, the clonal alternations were exclusively enriched in MPR group. Additionally, associations between HR gene alternations, percentage of viable tumor cells and HRD event were identified, which orchestrated tumor mutational burden (TMB), mutational intratumor heterogeneity (ITH), somatic copy number alteration (SCNA) ITH and clonal neoantigen load in patients. Validations in public cohorts further supported the generality of our findings.

We reported for the first time the association between HRD event and enhanced neoadjuvant immunotherapy response in lung cancer. The power of HRD event in patient therapeutic stratification persisted in multifaceted public cohorts. We propose that HR pathway gene status could serve as novel and additional indicators guiding immune-neoadjuvant and immunotherapy treatment decisions for NSCLC patients.

Diagnosis and management of severe congenital protein C deficiency (SCPCD): Communication from the SSC of the ISTH.

Acute Lymphoblastic Leukaemia

Severe congenital protein C deficiency (SCPCD) is rare and there is currently substantial variation in the management of this condition. A joint pr...