Tramadol as a fentanyl adulterant: Prevalence and management in a ToxIC Fentalog study prospective cohort.

Background: Tramadol is an adulterant of illicit opioids. As it is a serotonin-norepinephrine reuptake inhibitor as well as a μ-opioid agonist, tramadol adulteration may worsen overdose signs and symptoms or affect the amount of naloxone patients receive.

Methods: This is a multicenter, prospective cohort of adult patients with suspected opioid overdoses who presented to one of eight United States emergency departments and were included in the Toxicology Investigators Consortium's Fentalog Study.

AML classification in the year 2023: How to avoid a Babylonian confusion of languages.

In parallel to the 5th edition of the World Health Organization Classification of Haematolymphoid Tumours (WHO 2022), an alternative International Consensus Classification (ICC) has been proposed. To evaluate the impact of the new classifications on AML diagnoses and ELN-based risk classification, we analyzed 717 MDS and 734 AML non-therapy-related patients diagnosed according to the revised 4th WHO edition (WHO 2017) by whole genome and transcriptome sequencing. In both new classifications, the purely morphologically defined AML entities decreased from 13% to 5%.

Indeterminate and oncogenic potential: CHIP vs CHOP mutations in AML with NPM1 alteration.

In AML patients, recurrent mutations were shown to persist in remission, however, only some have a prognostic value and persistent mutations might therefore reflect a re-established premalignant state or truly active disease causing relapse. We aimed to dissect the nature of co-mutations in NPM1 mutated AML where the detection of NPM1 transcripts allows highly specific and sensitive detection of complete molecular remission (CMR). We analysed 150 consecutive patients who achieved CMR following intensive treatment by next generation sequencing on paired samples at diagnosis, CMR and relapse (38/150 patients).

Fulminant blast crisis with de novo 11q23 rearrangement in a Philadelphia-positive CML patient undergoing treatment with dasatinib.

Background: Progression of chronic myeloid leukemia (CML) is frequently accompanied by cytogenetic evolution, with an extra copy of the Philadelphia chromosome, trisomy 8 and 19, and isochromosome (17p) commonly detected. Translocations involving 11q23 chromosomal region have been rarely reported in CML. The few reported patients with blast crisis (BC) of CML carrying an 11q rearrangement have insufficient responses to tyrosine kinase inhibitors (TKIs) and possess a poor prognosis.

International external quality assurance of JAK2 V617F quantification.

External quality assurance (EQA) programs are vital to ensure high quality and standardized results in molecular diagnostics. It is important that EQA for quantitative analysis takes into account the variation in methodology. Results cannot be expected to be more accurate than limits of the technology used, and it is essential to recognize factors causing substantial outlier results.

mutated AML can relapse with wild-type : persistent clonal hematopoiesis can drive relapse.

Acute myeloid leukemia (AML) with mutation ( ) defines a World Health Organization entity. Absence of minimal residual disease (MRD) following induction chemotherapy is associated with an excellent prognosis. Data are conflicting on AML relapsing with wild-type We analyzed 104 paired samples of AML patients with relapse and identified 14/104 that relapsed with AML.

Genetic characterization of MYD88-mutated lymphoplasmacytic lymphoma in comparison with MYD88-mutated chronic lymphocytic leukemia.

MYD88 (myeloid differentiation primary response 88) is mutated in the majority of Waldenström macroglobulinemia/lymphoplasmacytic lymphoma (LPL); but also, albeit less frequently, in other B-cell malignancies, including chronic lymphocytic leukemia (CLL). This suggests MYD88 as a central regulator of pathogenesis, but requests a broader approach to define diagnostically relevant genetic profiles for LPL and CLL. We identified the L265P hotspot mutation in 86% (n=67/78) of our LPL and 2% (n=12/767) of our CLL cohort.

Gain of chromosome 21 or amplification of chromosome arm 21q is one mechanism for increased ERG expression in acute myeloid leukemia.

In acute myeloid leukemia (AML), acquired genomic gains and losses are common and lead to altered expression of genes located within or nearby the affected regions. Increased expression of the ETS-related transcription factor gene ERG has been described in myeloid malignancies with chromosomal rearrangements involving chromosome band 21q22, but also in cytogenetically normal AML, where it is associated with adverse prognosis. In this study, fluorescence in situ hybridization on interphase nuclei disclosed an amplification of the ERG gene (more than six copies) in 33 AML patients with structural rearrangements of 21q22.

WT1 mutations are secondary events in AML, show varying frequencies and impact on prognosis between genetic subgroups.

To investigate frequency and prognostic impact of Wilms tumor 1 (WT1) mutations (mut), we analyzed 3157 unselected acute myeloid leukemia patients for WT1mut in exons 7 and 9. In total, 188 WT1 mutations were detected (exon 7: n=150, exon 9: n=38); 141 were frameshift, 24 missense, 14 non-sense, 7 splice site and 2 indel mutations. In 175/3157 (5.

BAALC expression: a suitable marker for prognostic risk stratification and detection of residual disease in cytogenetically normal acute myeloid leukemia.

High brain and acute leukemia, cytoplasmic (BAALC) expression defines an important risk factor in cytogenetically normal acute myeloid leukemia (CN-AML). The prognostic value of BAALC expression in relation to other molecular prognosticators was analyzed in 326 CN-AML patients (<65 years). At diagnosis, high BAALC expression was associated with prognostically adverse mutations: FLT3 internal tandem duplication (FLT3-ITD) with an FLT3-ITD/FLT3 wild-type (wt) ratio of 0.

Flow cytometric identification of 76 patients with biclonal disease among 5523 patients with chronic lymphocytic leukaemia (B-CLL) and its genetic characterization.

Multiparameter flow cytometry (MFC) identifies rare cases of biclonal disease in chronic lymphocytic leukaemia (CLL). By MFC, we identified 76 patients with biclonal disease in a cohort of 5523 CLL patients (1·4%). Fluorescence in situ hybridization and chromosome banding analysis revealed five and six cases, respectively, with two different cytogenetic aberrations due to clonal evolution.