77 articles - From Friday Jan 06 2023 to Friday Jan 13 2023
Guidelines and related publications, position statements, white papers, technical reviews, consensus statements, etc…
| Am J Hematol |
Comparison of the International Consensus and 5th WHO edition classifications of adult myelodysplastic syndromes and acute myeloid leukemia. In this paper, we review and compare the two classifications in terms of diagnostic criteria and entity definition, with a focus on adult myelodysplastic syndromes/neoplasms (MDS) and acute myeloid leukemia (AML). The goal is to provide a tool to facilitate the work of pathologists, hematologists and researchers involved in the diagnosis and treatment of these hematological malignancies. |
meta-analyses and systematic reviews
| Thromb Haemost |
3-Factor versus 4-Factor Prothrombin Complex Concentrates for the Reversal of Vitamin K Antagonist-Associated Coagulopathy: A Systematic Review and Meta-analysis. Data were captured from 1,155 patients: 3F-PCC, = 0.23) nor in thromboembolisms was reported. These data suggest that 4F-PCC is better suited than 3F-PCC for the treatment of patients with VKA-associated coagulopathy, but further work is required for a definitive recommendation. |
RCT, clinical trials, retrospective studies, etc…
| Am J Hematol |
A Phase II Study of Combination Daunorubicin, Cytarabine (Ara-c) and Nilotinib (TAsigna) (DATA) in Patients Newly Diagnosed with Acute Myeloid Leukemia with KIT Expression. Only one patient (3%) died in induction due to liver failure, which was thought secondary to daunorubicin. Our current study reveals good outcomes in patients who received HCT and may warrant a larger study to confirm our findings in that specific population. |
Association of ABO mismatch with the outcomes of allogeneic hematopoietic cell transplantation for acute leukemia. Our study demonstrates that donor-recipient ABO status is independently associated with survival and other post-transplantation outcomes in acute leukemia. This underscores the importance of considering the ABO status in donor selection algorithms and its impact in acute leukemia. |
Checkpoint inhibitor-based salvage regimens prior to autologous stem cell transplant improve event-free survival in relapsed/refractory classic Hodgkin lymphoma. In this large multicenter retrospective study, CPI-based regimens improved EFS and PFS compared to other salvage regimens independent of pre-ASCT response. These data support earlier sequencing of CPI-based regimens in R/R cHL in the pre-ASCT setting. |
Chronic Myeloid Leukemia Without Major Molecular Response After 2 Years of Treatment with Tyrosine Kinase Inhibitor. The value of MMR was even less pronounced among patients aged 60 years or older at diagnosis, in whom mortality was primarily due to comorbidities unrelated to CML (10-year OS of 55% vs 10-year CML-OS of 100%). In conclusion, achievement of MCyR within two years is a reasonable milestone in CML, and these patients can still have good outcomes even when MMR is not achieved. |
Fludarabine versus cyclophospamide in combination with myeloablative total body irradiation as conditioning for patients with acute myeloid leukemia treated with allogeneic hematopoietic cell transplantation. A study from the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation. We conclude that for patients with AML treated with allo-HCT in CR, cyclophosphamide may be substituted with fludarabine in a regimen based on TBI at a dose of 12 Gy without negative impact on the efficacy. FluTBI12Gy is associated with reduced risk of grade 2-4 acute GVHD and encouraging survival rates. |
Intranasal Fentanyl and Discharge from the Emergency Department Among Children with Sickle Cell Disease and Vaso-occlusive Pain: A Multicenter Pediatric Emergency Medicine Perspective. The rapid onset of action and ease of delivery without IV access offered by intranasal fentanyl make it a feasible initial parenteral analgesic in the treatment of children with sickle cell disease presenting with vaso-occlusive pain episodes in the acute-care setting. Further study is needed to determine potential causality of the association between intranasal fentanyl and discharge from the emergency department observed in this multicenter study. |
Outcomes after Allogeneic Hematopoietic Cell Transplant in patients diagnosed with Blast Phase of Myeloproliferative Neoplasms: a retrospective study from the Chronic Malignancies Working Party of the EBMT. In this large series of BP-MPN patients, about one third were alive at 3 years after transplantation. Patients undergoing allo-HCT in the more recent era, with a KPS=90 and in CR at transplant had a better prognosis. |
Sequence analyses of relapsed or refractory diffuse large B-cell lymphomas unravel three genetic subgroups of patients and the GNA13 mutant as poor prognostic biomarker, results of LNH-EP1 study. GNA13 mutant was significantly associated with an increased risk of death (HR: 6.6 [95%CI: 2.1-20.6]; p=0.0011) and shorter overall survival (p=0.0340). At the time of relapse or refractory disease, three genetic subgroups of DLBCL patients were delineated, which could help advance precision molecular medicine programs. |
| Blood |
A phase II clinical trial of combined BRAF/MEK inhibition for BRAFV600E-mutated multiple myeloma. Emerging resistance to therapy was driven by RAS mutations and structural variants involving the BRAF locus. This is the first prospective clinical trial to demonstrate that combined BRAF/MEK inhibition is highly effective in patients with BRAFV600E mutated RRMM and represents a successful targeted precision medicine approach in this disease. |
Central Nervous System Status is Prognostic in T-Cell Acute Lymphoblastic Leukemia: A Children's Oncology Group Report. Unlike with B-ALL, CNS-2 status in T-ALL does not impact outcome in the context of aBFM therapy, without additional intrathecal therapy, with or without CRT. Although nelarabine improved outcomes for those with CNS-3 status, novel approaches are needed for further improvements. |
Hereditary platelet disorders associated with germline variants in RUNX1, ETV6 and ANKRD26. Partnered with this are continued technological developments, including rapid sharing of genetic variant information and automated integration with variant classification relevant data such as high throughput functional data. Collective progress in this area will drive timely diagnosis and, in time, leukemia preventative therapeutic interventions. |
High-Dose Melphalan Treatment Significantly Increases Mutational Burden at Relapse in Multiple Myeloma. This similarity could be due to HDM relapse samples having significantly more neoantigens. Overall, our study identifies increased genomic changes associated with HDM and provides rationale to further understand clonal complexity. |
Metabolism in stem cell driven leukaemia: parallels between haematopoiesis and immunity. These studies also offer detailed mechanisms that have yet to be investigated in leukaemia. Given that cancer (and normal) cells can meet their energy requirements by not only upregulating metabolic pathways, but also utilising systemically available substrates, we aim to inform how interlinked these metabolic pathways are, both within leukaemic cells and between cancer cells and their niche. |
MYB insufficiency disrupts proteostasis in hematopoietic stem cells leading to age-related neoplasia. Linking to previous studies showing the importance of proteostasis in HSC maintenance, we observed altered proteosomal activity in young Myb-insufficient mice as well as elevated proliferation indicators, followed later by elevated ribosome activity. We propose that these alterations combine to cause an imbalance in proteostasis, potentially creating a cellular milieu favoring disease initiation. |
Polatuzumab vedotin in previously untreated DLBCL: an Asia subpopulation analysis from the Phase 3 POLARIX trial. Safety was comparable between Pola-R-CHP and R-CHOP, including rates of grade 3-4 adverse events (AEs; 72.9% vs 66.2%, respectively), serious AEs (32.9% vs 32.4%), grade 5 AEs (1.4% vs 0.7%), AEs leading to study treatment discontinuation (5.0% vs 7.2%), and any-grade peripheral neuropathy (44.3% vs 50.4%). These findings demonstrate consistent efficacy and safety of Pola-R-CHP versus R-CHOP in the Asian and global populations in POLARIX. |
Rare Germline Complement Factor H Variants in Patients with Paroxysmal Nocturnal Hemoglobinuria. No CFH-variant patient had severe aplastic anemia from eculizumab initiation until six months. We show for the first time that rare CFH variants are over-represented among PNH patients and that germline genetic background may affect the response to eculizumab. |
Removal of the vicinal disulfide enhances the platelet capturing function of Von Willebrand Factor. Differential scanning calorimetry and Hydrogen-Deuterium exchange mass spectrometry demonstrate that reduction of the vicinal disulfide destabilizes the A2 domain which consequently disrupts interactions between the A1, A2, and A3 domains and enhances the conformational dynamics of A1-domain secondary structures known to regulate the strength of platelet adhesion to VWF. This study clarifies that the reduced state of the A2 vicinal disulfide is not inhibitory, but rather slightly activating. |
SBNO2 is a critical mediator of STAT3-driven hematological malignancies. In NPM-ALK T-ALCL patients, high SBNO2 expression correlates with shorter relapse-free- and overall survival. Our findings identify SBNO2 as potential therapeutic intervention site for STAT3-driven hematopoietic malignancies. |
Tracking the Evolution of Therapy-Related Myeloid Neoplasms Using Chemotherapy Signatures. Overall, we reveal a novel mode of tMN progression that is not reliant on direct mutagenesis or even exposure to chemotherapy. Conversely, for tMN that evolve under the influence of chemotherapy-induced mutagenesis, distinct chemotherapies not only select pre-existing CH, but also promote the acquisition of recurrent genomic drivers. |
Ubiquitin receptor PSMD4/Rpn10 is a novel therapeutic target in multiple myeloma. In MM xenograft models, SB was well-tolerated, inhibited tumor growth, and prolonged survival. Our data suggests that inhibiting Rpn10 will enhance cytotoxicity and overcome PI-resistance in MM, providing the basis for further optimization studies of Rpn10 inhibitors for clinical application. |
| Blood Adv |
A stem cell epigenome is associated with primary nonresponse to CD19 CAR T-cells in pediatric acute lymphoblastic leukemia. We thus describe the association of a Stem Cell Epigenome (SCE) with primary resistance to CD19-CAR therapy. Future trials incorporating these biomarkers, with addition of multi-specific CAR T-cells targeting against leukemic stem cell or myeloid antigens, and/or combined epigenetic therapy to disrupt this distinct stem cell epigenome may improve outcomes of patients with B-ALL. |
Analysis of immune responses in CLL patients after heterologous COVID-19 vaccination. Boosting was particularly effective when intrinsic immune status was improved by CLL-treatment. Limitations included study of a relatively small cohort receiving different treatments and vaccination schedules. |
Association of TIM-3 checkpoint receptor expression on T cells with treatment-free remission in chronic myeloid leukemia. Furthermore, gene expression analysis from publicly available datasets showed increased TIM-3 expression on CML stem cells compared with normal hematopoietic stem cells. These findings suggest that among the targetable immune checkpoint molecules, TIM-3 blockade may potentially improve effector immune response in CML patients stopping TKI, whilst concomitantly targeting leukemic stem cells, and could be a promising therapeutic strategy for preventing relapse after cessation of TKI in CML patients. |
Blockade of CCR1 induces a phenotypic shift in macrophages and triggers a favorable antilymphoma activity. Our study established that CCR1 exerts a pivotal role in macrophage programming, thus shaping protumor TME and lymphoma progression. CCR1 inhibition through CCR1 antagonists may be a promising therapeutic strategy to reprogram macrophages in lymphoma-TME and achieve better clinical outcomes in patients. |
CD19-CAR-T cells are an effective therapy of post-transplant relapse in B- ALL patients: Real-World Data from Germany. A total of 45.3% were rescued with a single dose of Tisa-cel. Our novel finding that ALL patients post-alloHSCT had by far a better pEFS if relapse occurred beyond 6 months might be helpful in clinical decision-making and motivates studies to uncover the reasons. |
Comorbidities in recipients of low transplant conditioning intensity regimens for acute myeloid leukemia: an ALWP EBMT study. In a combined model, cardiac, psychiatric, renal, and inflammatory bowel disease were independently associated with adverse transplantation outcomes. These findings may inform patient and regimen selection and reinforce the need for further investigation of cardioprotective transplantation approaches. |
Determinants of low health-related quality of life in patients with myelodysplastic syndromes: EUMDS registry study. Sex, KPS, comorbidity burden, hemoglobin count, and transfusion burden were determinants for al EQ-5D dimensions. Low HRQoL is determined by multiple factors, which should be considered in the management and shared decision making of patients with MDS. |
Haploidentical vs matched unrelated donors for patients with ALL: donor age matters more than donor type. Despite a higher risk of relapse, younger donor haploidentical HCT with PTCy prophylaxis may be preferred over an older MUD HCT with conventional prophylaxis in patients with ALL due to lower nonrelapse mortality and better OS. Further analysis comparing the effect of donor age in haploidentical-PTCy vs MUD-PTCy is warranted. |
| Blood Cancer J |
A pooled analysis of outcomes according to cytogenetic abnormalities in patients receiving ixazomib- vs placebo-based therapy for multiple myeloma. The HR for PFS with ixazomib- vs placebo-based therapy was 0.68 in patients with t(4; 14) (95% CI: 0.48-0.96; mPFS 22.4 vs 13.2 months), and 0.77 for patients with amp1q21 (95% CI: 0.63-0.93; mPFS 18.8 vs 14.5 months). A PFS benefit was demonstrated with ixazomib- vs placebo-based therapy regardless of cytogenetic status, with greatest benefit observed in patients with t(4; 14) and amp1q21. |
Pevonedistat, a Nedd8-activating enzyme inhibitor, in combination with ibrutinib in patients with relapsed/refractory B-cell non-Hodgkin lymphoma. Thus, pevonedistat combined with ibrutinib demonstrated safety and promising early efficacy in NHL and CLL. NAE inhibition downregulated NF |
Prolyl-tRNA synthetase as a novel therapeutic target in multiple myeloma. These include CD138, transcription factors such as MYC, and transcription factor 3 (TCF3), which we establish as a novel determinant in MM pathobiology through functional and genomic validation. Our preclinical data therefore provide evidence that blockade of prolyl-aminoacylation evokes a complex pro-apoptotic response beyond the canonical integrated stress response and establish a framework for its evaluation in a clinical setting. |
Risk of second primary malignancies in patients with chronic lymphocytic leukemia: a population-based study in the Netherlands, 1989-2019. The risk of SPMs was higher in CLL patients who received anti-neoplastic therapy (SIR, 2.12; 95% CI, 1.96-2.28), as compared with those who did not (SIR, 1.58; 95% CI, 1.53-1.63). Routine surveillance activities and tailored interventions to counteract the increased morbidity and excess mortality associated with SPMs are essential for improving long-term outcomes in CLL patients. |
| CA Cancer J Clin |
Cancer statistics, 2023. This progress increasingly reflects advances in treatment, which are particularly evident in the rapid declines in mortality (approximately 2% annually during 2016 through 2020) for leukemia, melanoma, and kidney cancer, despite stable/increasing incidence, and accelerated declines for lung cancer. In summary, although cancer mortality rates continue to decline, future progress may be attenuated by rising incidence for breast, prostate, and uterine corpus cancers, which also happen to have the largest racial disparities in mortality. |
| Haematologica |
E3-ligase TRIM31 regulates hematopoietic stem cell homeostasis and MLL-AF9 leukemia. Mechanistically, we found that ubiquitin-mediated degradation of CDK8 was impaired by TRIM31 deletion, which further induced transcriptional expression of PBX1 and Cyclin D1. Taken together, these findings reveal the function of TRIM31 in regulation of hematopoietic stem cell homeostasis and leukemia initiation; and indicate the physiological importance of TRIM31 in leukemia development at early stage of disease. |
High rate of durable responses with undetectable minimal residual disease with frontline venetoclax and rituximab in young and fit patients with chronic lymphocytic leukemia and an adverse biologic profile: results of the gimema phase II LLC1518 - 'Veritas' study. Three patients have died, two due to Covid-19 and 1 to tumor lysis syndrome. The first report of the VERITAS study shows that frontline VenR was associated with a high rate of CRs and durable responses with uMRD in young patients with CLL and unfavorable genetic characteristics. |
Low T-cell proportion in the tumor microenvironment is associated with immune escape and poor survival in diffuse large B-cell lymphoma. In addition, cases with loss of B2M, HLA I and/or HLA II protein expression on the tumor cells also had a low T-cell proportion, providing evidence that lack of these proteins allows for immune evasion. Overall, our results show that patients with DLBCL with a low T-cell proportion in the TME have a poor survival when treated with R-CHOP and exhibit mechanisms of immune escape. |
TAL1 activation in T-Cell acute lymphoblastic leukemia: A novel oncogenic 3' neoenhancer. Here, we demonstrate that this mutation leads to increased enhancer activity, gain of active epigenetic marks and TAL1 activation via recruitment of MYB. These results highlight the diversity of non-coding mutations that can drive oncogene activation. |
| Leukemia |
Molecular profiling of EBV associated diffuse large B-cell lymphoma. We have identified recurrent mutations activating the oncogenic JAK-STAT and NOTCH pathways as well as frequent amplifications of 9p24.1 contributing to immune escape by PD-L1 overexpression. Our findings enable further functional preclinical and clinical studies exploring the therapeutic potential of targeting these aberrations in patients with EBV + DLBCL to improve outcome. |
The histone demethylase KDM5C functions as a tumor suppressor in AML by repression of bivalently marked immature genes. This is accompanied by a de-differentiation phenotype that could be reversed by modulating levels of several direct and indirect downstream mediators. Finally, the association of KDM5C levels with long-term disease-free survival of female AML patients emphasizes the clinical relevance of our findings and identifies KDM5C as a novel female-biased tumor suppressor in AML. |
| Thromb Haemost |
BAY 81-8973 Efficacy and Safety in Previously Untreated and Minimally Treated Children with Severe Hemophilia A: The LEOPOLD Kids Trial. BAY 81-8973 was effective for bleed prevention and treatment in PUPs/MTPs. The observed inhibitor rate was strongly influenced by a cluster of inhibitor cases, and consequently, slightly higher than in other PUP/MTP studies. Overall, the BAY 81-8973 benefit-risk profile remains unchanged and supported by ongoing safety surveillance. Immune tolerance can be achieved with BAY 81-8973. |
Expression of microRNA Predicts Cardiovascular Events in Patients with Stable Coronary Artery Disease. Among patients with CAD, adding miR-223-3p expression to traditional cardiovascular risk factors may improve prediction of cardiovascular events, particularly ST. Clinical trials confirming these findings are warranted. |
P2Y12 Inhibition Suppresses Proinflammatory Platelet-Monocyte Interactions. Objectives To analyze the effect of platelets on monocyte activation and APT on MPA and platelet-induced monocyte activation. Methods Agonist-stimulated whole blood was incubated in the presence of P-selectin, PSGL1, PAR1, P2Y inhibition attenuates platelet-induced monocyte activation. |
Post-PCI Risk Assessment by Inflammation Activity According to Disease Acuity and Time from Procedure. Risk phenotype of hsCRPbaseline correlates with 1-month outcomes only in AMI patients. Whereas the prognostic implication of this risk phenotype appears similar during the late phase, irrespective of the disease acuity. |
Stroke and myocardial infarction in patients with abdominal aortic aneurysms and new-onset atrial fibrillation. Cardiovascular prognosis has improved in patients with prevalent AAA disease and new-onset AF in concordance with optimization of antithrombotic therapy over time. A diagnosis of AF conferred residual risk of stroke and myocardial infarction. |
Plenty of the editorials are available as full text through the publisher website using the provided link
| Blood |
| CA Cancer J Clin |
Chimeric antigen receptor T-cell therapy in multiple myeloma: A comprehensive review of current data and implications for clinical practice. Early studies have demonstrated remarkable response rates with CAR T-cell therapy in RRMM; however, durable responses with CAR T-cell therapies in myeloma have yet to be realized. In this comprehensive review, the authors describe the development of CAR T-cell therapies in myeloma, the outcomes of notable clinical trials, the toxicities and limitations of CAR T-cell therapies, and the strategies to overcome therapeutic challenges of CAR T cells in the hope of achieving a cure for multiple myeloma. |
Radiotheranostics in oncology: Making precision medicine possible. The palpable excitement in the field stems from the finding that a proportion of patients with large metastatic burden show complete and partial responses, and this outcome is catalyzing the search for more radiotheranostics approaches. Not every patient will benefit from radiotheranostics; but, for those who cross the target-detected line, the likelihood of response is very high. |
| Haematologica |
Aspirin in essential thrombocythemia: To whom? What formulation? What regimen? Although additional data on gastrointestinal tolerability will be useful, the bid regimen could already be implemented in clinical practice, considering its favorable risk/benefit profile. However, patients whose platelet count has been normalized could still be treated with the od regimen, because they would otherwise be unnecessarily exposed to a potential small risk of gastrointestinal discomfort. |
misc publications eg case reports, tools of the trade, images of the month, etc…
| Am J Hematol |
| Blood |
| Blood Adv |
| CA Cancer J Clin |
| Leukemia |
| Thromb Haemost |
Letters to the editors and authors’ replies
| Am J Hematol |
| Blood Cancer J |