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Clinical Case Reports May 2024In a patient with de novo AML, co-existing isoform and rearrangement is accompanied by a very poor prognosis including limited response to treatment and no molecular...
KEY CLINICAL MESSAGE
In a patient with de novo AML, co-existing isoform and rearrangement is accompanied by a very poor prognosis including limited response to treatment and no molecular remission. It is essential to develop a consensus on the therapeutic modalities different from the current regimen.
ABSTRACT
Acquisition of fusion as a primary or secondary event and fusion independently is reported in de novo and therapy-related MDS/AML, albeit with low frequency (<0.5%). Coexistence of and translocation is known to cause leukemogenesis in animal models and progression towards blast crisis CML but not AML. Here we report a unique case of pediatric AML with concomitant BCR::ABL1 and RUNX1::MECOM fusion.Routine diagnostic work-up included WBC manual differential, immunophenotype, morphology, qPCR, FISH, and NGS-based CNV analyses. The patient presented with history of fever, dizziness, fatigue, gingival bleeding, and epistaxis associated with ecchymosis in right hand and heavy, prolonged menstrual period. At presentation, her hemoglobin was 5.3 g/dL, WBC 52.1(10*9/L), PLT 10(10*9/L), ESR 5 mm/h and LDH 2658 U/L. Bone marrow was hypercellular with 71% blasts, and flow cytometry showed myeloid markers including CD11c, CD33, CD34, and CD45 among others indicating AML with monocytic differentiation. FISH analyses showed variant t(9;22) (q34.1;q11.1), one additional copy each of chromosome 8 and gene, while NGS-based CNV analyses revealed a terminal and proximal pathogenic gain within 9q34.12q34.3 and 22q11.1q11.23, respectively, and gain of entire chromosome 8 and 12 in mosaic state. qPCR confirmed the presence of and also revealed fusion. Patient received ADE (cytarabine, daunorubicin, and etoposide) induction regimen but required multiple ICU admissions due to sepsis, cardiac shock, acute myocarditis, and thyroiditis. Coexisting and fusion is suggestive of poor prognosis, and a need for consensus on the treatment modalities other than the current regimen is warranted.
PubMed: 38751957
DOI: 10.1002/ccr3.8917 -
Swiss Medical Weekly May 2024Until the year 2000, allogeneic haematopoietic cell transplantation (HCT) was the standard treatment for young and fit chronic myeloid leukaemia (CML) patients. CML was...
AIM
Until the year 2000, allogeneic haematopoietic cell transplantation (HCT) was the standard treatment for young and fit chronic myeloid leukaemia (CML) patients. CML was the main indication for allogeneic HCT. The introduction of tyrosine kinase inhibitors changed the treatment of CML patients dramatically. Allogeneic HCT was rapidly replaced by tyrosine kinase inhibitors as first-line treatment for CML, and the indication shifted to the treatment of non-responders, patients intolerant to tyrosine kinase inhibitors and patients whose CML is transforming to the accelerated phase and blast crisis. This paper describes changes in the use of transplantation technology for CML patients in the face of rapid drug development.
METHODS
All patients receiving a transplant for CML between 1997 and 2021 in Switzerland were included in the study. For the purpose of this analysis, time periods were analysed in quinquennia, 1997-2001 (Q1), 2002-2006 (Q2), 2007-2011 (Q3), 2012-2016 (Q4) and 2017-2021 (Q5), as the observation period spanned 25 years.
RESULTS
Overall, 239 patients received a transplant. These included 96 in Q1, 56 in Q2, 25 in Q3, 34 in Q4 and 28 in Q5. Patient characteristics changed over time: recent patients were older and had a longer interval from diagnosis to transplantation because of tyrosine kinase inhibitor treatment. However, the proportions of patients receiving transplants during an early versus advanced disease stage differed little. Transplant technology changed, as well. Patients received intensive conditioning regimens less often due to higher age and more commonly had peripheral blood as opposed to bone marrow transplants. However, the type of stem cell donor selected did not differ. In a univariable analysis, there were no significant differences in survival, progression-free survival, non-relapse mortality, relapse incidence or incidences of acute and chronic graft-versus-host disease among the five quinquennia. In a multivariable analysis, older age, donors other than HLA-identical siblings and more advanced disease stage, but not the quinquennium, were associated with higher risk of death.
CONCLUSION
Since the introduction of tyrosine kinase inhibitors haematopoietic cell transplantation has been used less frequently to treat CML. Patients in recent cohorts received transplants at an older age and later in the disease course; despite these higher risks, the outcome of allogeneic HCT has not worsened over time but has not improved, either. As the outcome is worse in advanced phases, it is important to conduct transplants before disease progression. Therefore, patients with advanced disease should be monitored closely and receive transplants in time.
Topics: Humans; Hematopoietic Stem Cell Transplantation; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Switzerland; Male; Female; Adult; Middle Aged; Transplantation, Homologous; Protein Kinase Inhibitors; Adolescent; Transplantation Conditioning
PubMed: 38749067
DOI: 10.57187/s.3754 -
Materials (Basel, Switzerland) Apr 2024Aiming to enhance the comprehensive utilization of steel slag (SS), a solid waste-based binder consisting of SS, granulated blast furnace slag (BFS), and desulfurization...
Aiming to enhance the comprehensive utilization of steel slag (SS), a solid waste-based binder consisting of SS, granulated blast furnace slag (BFS), and desulfurization gypsum (DG) was designed and prepared. This study investigated the reaction kinetics, phase assemblages, and microstructures of the prepared solid waste-based cementitious materials with various contents of SS through hydration heat, XRD, FT-IR, SEM, TG-DSC, and MIP methods. The synergistic reaction mechanism between SS and the other two wastes (BFS and DG) is revealed. The results show that increasing SS content in the solid waste-based binder raises the pH value of the freshly prepared pastes, advances the main hydration reaction, and shortens the setting time. With the optimal SS content of 20%, the best mechanical properties are achieved, with compressive strengths of 19.2 MPa at 3 d and 58.4 MPa at 28 d, respectively. However, as the SS content continues to increase beyond 20%, the hydration process of the prepared binder is delayed. The synergistic activation effects between SS and BFS with DG enable a large amount of ettringite (AFt) formation, guaranteeing early strength development. As the reaction progresses, more reaction products CSH and Aft are precipitated. They are interlacing and overlapping, jointly refining and densifying the material's microstructure and contributing to the long-term strength gain. This study provides a reference for designing and developing solid waste-based binders and deepens the insightful understanding of the hydration mechanism of the solid waste-based binder.
PubMed: 38730808
DOI: 10.3390/ma17091999 -
Centrality dependency of proton, deuteron, and triton's temperatures in Au+Au collisions at 200 GeV.Scientific Reports May 2024The transverse momentum (p) spectra of protons (p), deuterons (d), and tritons (t) in 200 GeV gold-gold (Au + Au) collisions at RHIC are examined across a range of...
The transverse momentum (p) spectra of protons (p), deuterons (d), and tritons (t) in 200 GeV gold-gold (Au + Au) collisions at RHIC are examined across a range of centrality bins using the Levy Tsallis (TS) statistical model. The model's predictions closely match the experimental results from PHENIX (p) and STAR (d and t) Collaborations. Kinetic freeze-out temperatures of hadrons are obtained from particle spectra. The results showed that the kinetic freeze-out temperature decreases as collisions move from center to the periphery. This work found mass-dependent kinetic freeze-out temperatures, heavier particles arrive to the freeze-out phase before lighter ones. Comparison with same data fitted by blast wave function with Tsallis statistics (BWTS) showed that T values are increasing from central to peripheral collisions, while in case of TS function (current analysis) it decreases. This behavior puts a question mark on the reliability of using such functions for temperature extraction.
PubMed: 38704383
DOI: 10.1038/s41598-024-55759-2 -
Leukemia Research Reports 2024T-cell acute lymphoblastic leukemia/lymphoma (T-ALL/LBL) is a rare and aggressive leukemia. Philadelphia chromosome-positive cytogenetic abnormality is most common in...
A rare case of Philadelphia-positive (P210BCR-ABL1) T-cell acute lymphoblastic leukemia/lymphoma associated with minimal residual disease persistence after intensive chemotherapeutic approaches.
T-cell acute lymphoblastic leukemia/lymphoma (T-ALL/LBL) is a rare and aggressive leukemia. Philadelphia chromosome-positive cytogenetic abnormality is most common in CML. It is difficult to differentiate between de novo Ph+ T-ALL/LBL and T-cell lymphoblastic crises of CML. We present a case of adult Ph+ T-ALL/LBL with a likely history of antecedent CML. Initially thought to be a case of chronic-phase CML, a diagnostic quandary led to the pursuit of a lymph node biopsy that established the diagnosis of Ph+ T-LBL or T lymphoblastic blast crisis of CML, a clinical presentation extremely rare and only the second of its kind from our review of the literature. The patient was treated with an intensive chemotherapy regimen for over a year due to persistent minimal residual disease (MRD) positivity indicating aggressive disease.
PubMed: 38572397
DOI: 10.1016/j.lrr.2024.100456 -
A chronic myeloid leukemia present with an unusual relapse in central nervous system: A case report.Clinical Case Reports Apr 2024Extramedullary involvement of the central nervous system (CNS) in Chronic Myeloid Leukemia (CML) is an uncommon relapse. In this case, we present a unique instance of a...
Extramedullary involvement of the central nervous system (CNS) in Chronic Myeloid Leukemia (CML) is an uncommon relapse. In this case, we present a unique instance of a 43-year-old male diagnosed with CML experiencing a CNS blast crisis.
PubMed: 38550723
DOI: 10.1002/ccr3.8671 -
Leukemia May 2024Blast phase (BP) of chronic myeloid leukemia (CML) still represents an unmet clinical need with a dismal prognosis. Due to the rarity of the condition and the...
Management and outcome of patients with chronic myeloid leukemia in blast phase in the tyrosine kinase inhibitor era - analysis of the European LeukemiaNet Blast Phase Registry.
Blast phase (BP) of chronic myeloid leukemia (CML) still represents an unmet clinical need with a dismal prognosis. Due to the rarity of the condition and the heterogeneity of the biology and clinical presentation, prospective trials and concise treatment recommendations are lacking. Here we present the analysis of the European LeukemiaNet Blast Phase Registry, an international collection of the clinical presentation, treatment and outcome of blast phases which had been diagnosed in CML patients after 2015. Data reveal the expected heterogeneity of the entity, lacking a clear treatment standard. Outcomes remain dismal, with a median overall survival of 23.8 months (median follow up 27.8 months). Allogeneic stem cell transplantation (alloSCT) increases the rate of deep molecular responses. De novo BP and BP evolving from a previous CML do show slightly different features, suggesting a different biology between the two entities. Data show that outside clinical trials and in a real-world setting treatment of blast phase is individualized according to disease- and patient-related characteristics, with the aim of blast clearance prior to allogeneic stem cell transplantation. AlloSCT should be offered to all patients eligible for this procedure.
Topics: Humans; Blast Crisis; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Registries; Protein Kinase Inhibitors; Middle Aged; Male; Adult; Female; Aged; Young Adult; Transplantation, Homologous; Europe; Hematopoietic Stem Cell Transplantation; Prognosis; Adolescent; Treatment Outcome; Survival Rate; Disease Management; Follow-Up Studies; Tyrosine Kinase Inhibitors
PubMed: 38548962
DOI: 10.1038/s41375-024-02204-y -
PloS One 2024Injury related to blast exposure dramatically rose during post-911 era military conflicts in Iraq and Afghanistan. Mild traumatic brain injury (mTBI) is among the most...
Injury related to blast exposure dramatically rose during post-911 era military conflicts in Iraq and Afghanistan. Mild traumatic brain injury (mTBI) is among the most common injuries following blast, an exposure that may not result in a definitive physiologic marker (e.g., loss of consciousness). Recent research suggests that exposure to low level blasts and, more specifically repetitive blast exposure (RBE), which may be subconcussive in nature, may also impact long term physiologic and psychological outcomes, though findings have been mixed. For military personnel, blast-related injuries often occur in chaotic settings (e.g., combat), which create challenges in the immediate assessment of related-injuries, as well as acute and post-acute sequelae. As such, alternate means of identifying blast-related injuries are needed. Results from previous work suggest that epigenetic markers, such as DNA methylation, may provide a potential stable biomarker of cumulative blast exposure that can persist over time. However, more research regarding blast exposure and associations with short- and long-term sequelae is needed. Here we present the protocol for an observational study that will be completed in two phases: Phase 1 will address blast exposure among Active Duty Personnel and Phase 2 will focus on long term sequelae and biological signatures among Veterans who served in the recent conflicts and were exposed to repeated blast events as part of their military occupation. Phase 2 will be the focus of this paper. We hypothesize that Veterans will exhibit similar differentially methylated regions (DMRs) associated with changes in sleep and other psychological and physical metrics, as observed with Active Duty Personnel. Additional analyses will be conducted to compare DMRs between Phase 1 and 2 cohorts, as well as self-reported psychological and physical symptoms. This comparison between Service Members and Veterans will allow for exploration regarding the natural history of blast exposure in a quasi-longitudinal manner. Findings from this study are expected to provide additional evidence for repetitive blast-related physiologic changes associated with long-term neurobehavioral symptoms. It is expected that findings will provide foundational data for the development of effective interventions following RBE that could lead to improved long-term physical and psychological health.
Topics: Humans; United States; Veterans; Brain Injuries; Military Personnel; Brain Concussion; Blast Injuries; Sleep; Stress Disorders, Post-Traumatic; Iraq War, 2003-2011; Afghan Campaign 2001-; Observational Studies as Topic
PubMed: 38536869
DOI: 10.1371/journal.pone.0301026 -
Annals of Hematology May 2024Clinical trials in chronic myeloid leukemia (CML) are usually carried out in specialized centers whereas primary care for patients (pts) with CML is mainly provided by...
Clinical trials in chronic myeloid leukemia (CML) are usually carried out in specialized centers whereas primary care for patients (pts) with CML is mainly provided by local oncology practices. The aim of this study was to assess treatment practices in pts with CML in the setting of private oncology practices in Germany. We collected data of 819 pts with a confirmed diagnosis (dx) of CML in 2013 or later from 43 practices. At dx, 84.2% (n=690) and 9.4% (n=77) of pts were in chronic or accelerated phase, 0.7% (n=6) had a blast crisis. Molecular monitoring was provided by EUTOS certified laboratories in 87.7% of pts. Typical BCR::ABL1 transcripts were detected in 86.6% (n=709). Molecular response was assessed after 2.8, 6.0, 9.4 and 12.9 m (mean) after start of treatment. Of the pts with available data, 11.1% did not achieve early molecular response and at 18 m, 83.7% had at least a major molecular response. 288 (35.2%) of pts switched to 2 line (2L) treatment after a mean of 21.0 months. Reasons for 2L treatment were side effects in 43.4% and suboptimal response or failure in 31.4% of pts. 106 pts went on to third line (3L) treatment. 36.8 % of pts switched to and 92.8 % of pts still on 3L treatment achieved BCR::ABL1 ≤1% at 12 m. In conclusion, in Germany pts with CML are routinely monitored by qPCR and good responses are achieved in the majority. Treatment changes are mainly due to adverse events rather than suboptimal responses.
Topics: Humans; Retrospective Studies; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Blast Crisis; Germany; Fusion Proteins, bcr-abl; Protein Kinase Inhibitors
PubMed: 38472361
DOI: 10.1007/s00277-024-05702-2 -
Middle East African Journal of... 2023The purpose is to to explore the effects of the Lebanese economic crisis on the ophthalmology workload in Lebanon, and the concomitant influence of the COVID-19-related...
PURPOSE
The purpose is to to explore the effects of the Lebanese economic crisis on the ophthalmology workload in Lebanon, and the concomitant influence of the COVID-19-related lockdown and Beirut port explosion.
METHODS
Data pertaining to all the clinic visits to the Ophthalmology Department at the American University of Beirut Medical Center between January 01, 2019, and December 31, 2021, were extracted. Completed visits to different subspecialties were used to analyze the different parameters. All parameters were compared across the 3 years.
RESULTS
We included 102,810 completed visits in this study. A total decrease of 15.3% occurred in visits between 2019 and 2020. The mean number of patients per month decreased significantly between 2019 and 2020 in retina/uveitis and glaucoma/anterior segment clinics. The same trend was observed in pediatric/neuro-ophthalmology and cornea/refractive surgery, although it did not reach statistical significance. For oculoplastics, the workload actually tended to increase from 2019 to 2021. During the pandemic-related lockdown (March, April, and May 2020), the workload decreased by 37.8% in oculoplastics, 63.4% in pediatric/neuro-ophthalmology, 52.8% in retina/uveitis, 60.2% in cornea/refractive surgery, and 50.7% in glaucoma/anterior segment. After the Beirut port explosion in August 2020, an overall decrease of 30.2% was found in the number of patient visits in all sub-specialties, while the number of patients in oculoplastics remained nearly unchanged.
CONCLUSION
The ophthalmology workload was strongly affected by the economic crisis in all subspecialties especially with the pandemic in 2020, except for oculoplastics. During the pandemic, the most affected subspecialty was the pediatric/neuroophthalmology, while oculoplastics was the least affected.
Topics: Humans; Child; Ophthalmology; Pandemics; Workload; Glaucoma; Uveitis
PubMed: 38435110
DOI: 10.4103/meajo.meajo_130_23