29 research outputs found
Absence of BCL-2 expression identifies a subgroup of AML with distinct phenotypic, molecular, and clinical characteristics
Acute myeloid leukemia (AML) is a hematologic malignancy characterized by the rapid and uncontrolled clonal growth of myeloid lineage cells in the bone marrow. The advent of oral, selective inhibitors of the B-cell leukemia/lymphoma-2 (BCL-2) apoptosis pathway, such as venetoclax, will likely induce a paradigm shift in the treatment of AML. However, the high cost of this treatment and the risk of additive toxicity when used in combination with standard chemotherapy represent limitations to its use and underscore the need to identify which patients are most-and least-likely to benefit from incorporation of venetoclax into the treatment regimen. Bone marrow specimens from 93 newly diagnosed AML patients were collected in this study and evaluated for BCL-2 protein expression by immunohistochemistry. Using this low-cost, easily, and readily applicable analysis method, we found that 1 in 5 AML patients can be considered as BCL-2(-). In addition to a lower bone marrow blast percentage, this group exhibited a favorable molecular profile characterized by lower WT1 expression and underrepresentation of FLT3 mutations. As compared to their BCL-2(+) counterparts, the absence of BCL-2 expression was associated with a favorable response to standard chemotherapy and overall survival, thus potentially precluding the necessity for venetoclax add-on
A novel haemocytometric COVID-19 prognostic score developed and validated in an observational multicentre European hospital-based study
COVID-19 induces haemocytometric changes. Complete blood count changes, including new cell activation parameters, from 982 confirmed COVID-19 adult patients from 11 European hospitals were retrospectively analysed for distinctive patterns based on age, gender, clinical severity, symptom duration, and hospital days. The observed haemocytometric patterns formed the basis to develop a multi-haemocytometric-parameter prognostic score to predict, during the first three days after presentation, which patients will recover without ventilation or deteriorate within a two-week timeframe, needing intensive care or with fatal outcome. The prognostic score, with ROC curve AUC at baseline of 0.753 (95% CI 0.723-0.781) increasing to 0.875 (95% CI 0.806-0.926) on day 3, was superior to any individual parameter at distinguishing between clinical severity. Findings were confirmed in a validation cohort. Aim is that the score and haemocytometry results are simultaneously provided by analyser software, enabling wide applicability of the score as haemocytometry is commonly requested in COVID-19 patients
Dendritic cell vaccination as postremission treatment to prevent or delay relapse in acute myeloid leukemia
Relapse is a major problem in acute myeloid leukemia (AML) and adversely impacts survival.
In this phase II study, we investigated the effect of vaccination with dendritic cells (DCs)
electroporated with Wilms’ tumor 1 (WT1) mRNA as post-remission treatment in 30 AML
patients at very high risk of relapse. There was a demonstrable anti-leukemic response in 13
patients. Nine patients achieved molecular remission as demonstrated by normalization
of WT1 transcript levels, 5 of which are sustained after a median follow-up of 109.4 months.
Disease stabilization was achieved in 4 other patients. Five-year overall survival (OS) was
higher in responders than in non-responders (53.8% vs. 25.0%; P=0.01). In patients
receiving DCs in first complete remission (CR1), there was a vaccine-induced relapse
reduction rate of 25% and the 5-year relapse-free survival was higher in responders than in
non-responders (50% vs. 7.7%; P65 years who received DCs
in CR1, 5-year OS was 69.2% and 30.8% respectively, as compared to 51.7% and 18% in
the Swedish Acute Leukemia Registry (SALR). Long-term clinical response was correlated
with increased circulating frequencies of poly-epitope WT1-specific CD8+ T-cells. Long-term
OS was correlated with interferon-γ+ and tumor necrosis factor-α+ WT1-specific responses in delayed type hypersensitivity-infiltrating CD8+ T-lymphocytes. In conclusion, vaccination of
AML patients with WT1 mRNA-electroporated DCs can be an effective strategy to prevent or
delay relapse after standard chemotherapy, translating into improved OS rates, which are
correlated with the induction of WT1-specific CD8+ T-cell response. This trial was registered
at www.clinicaltrials.gov as #NCT00965224
A novel haemocytometric covid-19 prognostic score developed and validated in an observational multicentre european hospital-based study
COVID-19 induces haemocytometric changes. Complete blood count changes, including new cell activation parameters, from 982 confirmed COVID-19 adult patients from 11 European hospitals were retrospectively analysed for distinctive patterns based on age, gender, clinical severity, symptom duration and hospital days. The observed haemocytometric patterns formed the basis to develop a multi-haemocytometric-parameter prognostic score to predict, during the first three days after presentation, which patients will recover without ventilation or deteriorate within a two-week timeframe, needing intensive care or with fatal outcome. The prognostic score, with ROC curve AUC at baseline of 0.753 (95% CI 0.723-0.781) increasing to 0.875 (95% CI 0.806-0.926) on day 3, was superior to any individual parameter at distinguishing between clinical severity. Findings were confirmed in a validation cohort. Aim is that the score and haemocytometry results are simultaneously provided by analyser software, enabling wide applicability of the score as haemocytometry is commonly requested in COVID-19 patients
Human salivary cortisol, part I : development and full validation of an LC-MS/MS based method
Human salivary cortisol, part II: evaluation of an electrochemiluminescence immunoassay (Roche)
Routine serum creatinine measurements: how well do we perform?
The first aim of the study was to investigate the accuracy and intra-laboratory variation of serum creatinine measurements in clinical laboratories in Flanders. The second purpose was to check the effect of this variation in serum creatinine concentration results on the calculated estimated glomerular filtration rate (eGFR) and the impact on classification of patients into a chronic kidney disease (CKD) stage.status: publishe