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In CLL data from chromosome banding analysis (CBA) have been scarce due to the low proliferative activity of CLL cells in vitro. We improved the cultivation technique using an immunostimulatory CpG-oligonucleotide DSP30 and IL-2. A total of 506 CLL samples were analysed with CBA and interphase FISH using probes for the detection of trisomy 12, IgH rearrangements and deletions of 6q21, 11q22.3 (ATM), 13q14 (D13S25 and D13S319) and 17p13 (TP53). A total of 500 of 506 (98.8%) cases were successfully stimulated for metaphase generation and are subject to this study. Aberrations were detected in 415 of 500 (83.0%) cases by CBA and in 392 of 500 (78.4%) cases by FISH. CBA detected 832 abnormalities and FISH only 502. Therefore, CBA offers important information in addition to FISH. (1) CLL is characterized mainly by genomic imbalances and reciprocal translocations are rare. (2) A subgroup with complex aberrant karyotype (16.4%) is identified which is associated with an unmutated IgVH status and CD38 expression (P=0.034 and 0.02, respectively). (3) Additional abnormalities are detectable providing new biological insights into different CLL subclasses revealing a much more heterogeneous pattern of cytogenetic abnormalities as assumed so far based on FISH data only. Therefore, prospective clinical trials should evaluate the prognostic impact of newly available CBA data.Leukemia (2007) 21, 2442–2451; doi:10.1038/sj.leu.2404935; published online 6 September 2007 [ABSTRACT FROM AUTHOR]

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. Patient serum was analyzed via liquid chromatography quadrupole time-of-flight mass spectroscopy to detect opioids, novel psychoactive substances, and adulterants. Patients were separated into groups of those with tramadol detected versus no tramadol detected. Differences in naloxone administration, intubation, performance of cardiopulmonary resuscitation (CPR), or death between those exposed or not exposed to tramadol were evaluated., Results: From September 21, 2020 - October 31, 2021; 2298 patients were screened and 537 met inclusion criteria. Eighty-one patients (15 %) tested positive for tramadol. There was no significant difference found between those who reported chronic prescription opioid use (p = 0.81) or reported chronic pain (p = 0.27). Additionally, no difference was found between groups in the number of patients receiving a single, second, or third dose of naloxone (p = 0.25; 0.92; 0.59) or the proportion initiated on a naloxone infusion (p = 0.84). Similarly, there was no difference in outcomes of intubation, CPR, or death (p = 0.26; 0.75; 0.29)., Conclusions: Tramadol was identified in a subset of patients presenting to the Emergency Department with opioid overdoses suggesting adulteration of illicitly manufactured fentanyl with tramadol. Its presence was not associated with a lack of treatment response, difference in severity of overdose, or increased risk of complications., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Alex Manini, MD, MS: Research reported in this publication was supported by the National Institute on Drug Abuse of the National Institutes of Health under Award Number R01DA048009 (PI: Alex Manini). Supplemental funding is provided by the Centers for Disease Control and Prevention (Award Number 3R01DA048009-04S1) to increase the project's testing capacity. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health or the Centers for Disease Control and Prevention. Sharon Campleman, PhD: Serves as treasurer for the Public Health Research Institute of Southern California (PHRISC) for the past three years to current. No payments have been made to Dr. Campleman or PHRISC related to American College of Medical Toxicology work of the research presented in this submission. PHRISC oversees public health projects in Los Angeles not related to the opioid crisis., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Competing Interests: Torsten Haferlach, Claudia Haferlach, and Wolfgang Kern declare part ownership of Munich Leukemia Laboratory (MLL). Heiko Müller, Frank Dicker, Constance Bär, Wencke Walter, Stephan Hutter, Niroshan Nadarajah, and Manja Meggendorfer are employed by the MLL. Charles G. Mullighan received research funding from Loxo Oncology, Pfizer, AbbVie; honoraria from Amgen and Illumina, and holds stock in Amgen.

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%. Myelodysplasia-related (MR) AML increased from 22% to 28% (WHO 2022) and 26% (ICC). Other genetically-defined AML remained the largest group, and the abandoned AML-RUNX1 was mainly reclassified as AML-MR (WHO 2022: 77%; ICC: 96%). Different inclusion criteria of AML-CEBPA and AML-MR (i.a. exclusion of TP53 mutated cases according to ICC) were associated with differences in overall survival. In conclusion, both classifications focus on more genetics-based definitions with similar basic concepts and a large degree of agreement. The remaining non-comparability (e.g., TP53 mutated AML) needs additional studies to definitely answer open questions on disease categorization in an unbiased way., (© 2023. The Author(s).)

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). Patients with persistence or the acquisition of non-DTA (DNMT3A, TET2, ASXL1) mutations at CMR (23/150 patients, 15%) have a significantly worse prognosis (EFS HR = 2.7, p = 0.003; OS HR = 3.6, p = 0.012). Based on clonal evolution analysis of diagnostic, CMR and relapse samples, we redefine pre-malignant mutations and include IDH1, IDH2 and SRSF2 with the DTA genes in this newly defined group. Only the persistence or acquisition of CHOP-like (clonal hematopoiesis of oncogenic potential) mutations was significantly associated with an inferior outcome (EFS HR = 4.5, p = 0.0002; OS HR = 5.5, p = 0.002). Moreover, the detection of CHOP-like mutations at relapse was detrimental (HR = 4.5, p = 0.01). We confirmed these findings in a second independent whole genome sequencing cohort., (© 2021. The Author(s).)