112 articles - From Friday Jan 20 2023 to Friday Jan 27 2023
Guidelines and related publications, position statements, white papers, technical reviews, consensus statements, etc…
| Ann Oncol |
| Blood |
meta-analyses and systematic reviews
| Haematologica |
Deep learning applications in visual data for benign and malignant hematological conditions: a systematic review and visual glossary. This narrative review provides a visual glossary for key deep learning principles as well as a systematic review of published investigations within malignant and non-malignant hematological conditions, organized by the different phases of clinical care. In order to assist the unfamiliar reader, this review highlights key portions of current literature and summarizes important considerations for the critical understanding of deep learning development and implementations in clinical practice. |
RCT, clinical trials, retrospective studies, etc…
| Am J Hematol |
Orelabrutinib in relapsed or refractory chronic lymphocytic leukemia/small lymphocytic lymphoma patients: Multi-center, single-arm, open-label, phase 2 study. Nearly 67% of patients were still receiving orelabrutinib after almost a 3-year follow-up. In conclusion, Orelabrutinib demonstrated compelling efficacy as well as safety profiles, with a noteworthy number of patients obtaining complete response in refractory or relapsed CLL/SLL. |
Primary myelofibrosis: 2023 update on diagnosis, risk-stratification, and management. New directions New agents, alone or in combination with ruxolitinib, are currently under clinical trial investigation (ClinicalTrials. gov) and preliminary results were presented at the 2022 ASH annual meeting and highlighted in the current review. |
The Outcomes of Patients with Chronic Myeloid Leukemia Treated with Third-line BCR::ABL1 Tyrosine Kinase Inhibitors. By multivariate analysis, third-line therapy with ponatinib was the only independent factor associated with better survival (P = 0.003). In conclusion, ponatinib is an optimal treatment for patients with CML-CP failing 2 prior TKIs. |
Venous Thromboembolism after COVID-19 Vaccination in Patients with Thrombophilia. In this subgroup of COVID-19 vaccinated patients with thrombophilia, there was no increased risk for acute VTE post-vaccination compared to the prevaccination timeframe. These results are consistent with prior studies and should offer additional reassurance to patients with inherited or acquired thrombophilia. |
| Ann Oncol |
Survival update of neoadjuvant ipilimumab plus nivolumab in macroscopic stage III melanoma in the OpACIN and OpACIN-neo trials. Updated data confirm the high survival rates after neoadjuvant combination checkpoint inhibition in macroscopic stage III melanoma, especially for patients with pathologic response. Pathologic response is the strongest surrogate marker for long-term outcome. |
| Blood |
A practical approach to curate clonal hematopoiesis of indeterminate potential in human genetic datasets. We also find a significantly lower prevalence of CHIP in individuals of self-reported Latino or Hispanic ethnicity in All of Us, highlighting the importance of including diverse populations. The standardization of CHIP calling will increase the fidelity of CHIP epidemiological work and is required for clinical CHIP diagnostic assays. |
Activated granulocytes and inflammatory cytokine signaling drive T-cell lymphoma progression and disease symptoms. Furthermore, unselective JAK kinase inhibitors (ruxolitinib) inhibited both, TCL progression and granulocyte activation in various PTCL mouse models. Our results support the important role of granulocyte-driven inflammation, cytokine-induced granulocyte/CD4+ TCL interactions and the requirement of an intact JAK/STAT signaling pathway for PTCL-TFH development, and support broad JAK kinase inhibition as an effective treatment strategy in early disease stages. |
Aging alters the cell cycle control and mitogenic signaling responses of human hematopoietic stem cells. Importantly, subsequent dose-response analyses revealed an age-associated reduction in the growth-factor stimulated proliferation of CD49f+ cells mediated by reduced intrinsic activation of AKT and altered cell-cycle entry and progression. These findings identify a new intrinsic, pervasive, and progressive aging-related alteration in the biological and signaling mechanisms required to drive the proliferation of very primitive normal human hematopoietic cells. |
Approach to Bleeding in the Hospitalized Patient. Patients with no history of bleeding, for whom other causes, such as liver dysfunction, medication effect, disseminated intravascular coagulation or certain vitamin deficiencies have been ruled out may require evaluation for acquired coagulopathies, such as acquired hemophilia or acquired von Willebrand disease. Here we present three cases to discuss the diagnosis and management of the two most common acquired bleeding disorders, as well as a congenital bleeding disorder patient with a historical diagnosis. |
C1 inhibitor deficiency enhances contact pathway mediated activation of coagulation and venous thrombosis. These findings suggest a key role for endogenous C1INH as a negative regulator of contact pathway-mediated coagulation in humans and mice. Further, this work identifies endogenous C1INH as an important negative regulator of venous thrombus formation in mice complementing the phenotype associated with C1INH-HAE. |
How I Treat Multiple myeloma in the geriatric patient. Here we present 2 patient cases derived from clinical practice. We review current frailty scores and standards of care for elderly newly diagnosed patients with MM, including frail subgroups, and discuss ways to tailor treatment as well as treatment perspectives in this population. |
Potentiating antibody-dependent killing of cancers with CAR T cells secreting CD47-SIRPa checkpoint blocker. Local secretion of the CD47 inhibitor bypasses the CD47 sink found on al cells in the body and may prevent systemic toxicities. This combination of CAR T cell therapy, local CD47 blockade, and orthogonal antibody may be a combinatorial strategy to overcome the limitations of each individual monotherapy. |
| Blood Adv |
A Critical Role of RUNX1 in Governing Megakaryocyte-Primed Hematopoietic Stem Cell Differentiation. Further bulk RNAseq and Cut & Run analyses show that RUNX1 binds to multiple essential megakaryocyte/platelet developmental genes such as Spi1, Selp and Itga2b and regulates their expressions in MK-HSCs. Thus, by modulating the expression of megakaryocyte-related genes, RUNX1 governs the direct differentiation of MK-HSCs to megakaryocytes and platelets. |
Acalabrutinib and High-Frequency Low-Dose Subcutaneous Rituximab for Initial Therapy of Chronic Lymphocytic Leukemia. At a median follow-up of 2.3 years two patients with high-risk features have progressed while on acalabrutinib monotherapy. We conclude that HFLD rituximab in combination with acalabrutinib is an effective and tolerable self-administered home combination that provides a platform to build upon future regimens that may more reliably allow for fixed-duration therapy. |
BTK and PLCG2 remain unmutated in one third of patients with CLL relapsing on ibrutinib. Finally, no difference in TP53 mutation burden was observed between BTKmut versus BTKwt relapsing cases, and ibrutinib treatment did not appear to favor selection of TP53-aberrant clones. In conclusion, we show that BTK/PLCG2 mutations were absent in a substantial fraction (35%) of a real-world cohort failing ibrutinib, and propose additional mechanisms contributing to resistance. |
CMV reactivation after allogeneic HCT is associated with a reduced risk of relapse in acute lymphoblastic leukemia. A post-hoc subgroup analysis that combined AML and ALL showed that CMVR had a mild anti-leukemia effect without effect modification in contrast to the impact of CMVR on NRM. Our findings may provide important implications for the strategy used for CMV prophylaxis after HCT. |
Darinaparsin in Patients with Relapsed or Refractory Peripheral T-Cell Lymphoma: Results of an Asian Phase 2 Study. Darinaparsin is effective and well tolerated, with TEAEs that were clinically acceptable and manageable with symptomatic treatment and dose reductions (ClinicalTrials. gov: NCT02653976). |
Gata2-regulated Gfi1b expression controls endothelial programming during endothelial-to-hematopoietic transition. Finally, we show that hematopoietic-specific induction of gfi1b can restore HSC production in gata2b-null (gata2b-/-) zebrafish embryos. This study illustrates pivotal roles of Gata2 on the regulation of transcriptional network governing HSPC identity throughout EHT. |
Kindlin-3 deficiency leads to impaired erythropoiesis and erythrocyte cytoskeleton. Taken together, these findings document that erythroid and macrophage K3 are critical contributors to erythropoiesis in integrin-dependent manner while F-actin binding to K3 maintains the membrane cytoskeletal integrity and erythrocyte biconcave shape. The dual function of K3 in erythrocytes and in erythroblastic islands establish an important functional role for K3 in normal erythroid function. |
Large case-control study indicates no association of KIR genotype and risk of developing acute myeloid leukemia. Using information on KIRs and their HLA ligands, we further tested receptor-ligand models and summation models without revealing markedly significant differences between patients and controls, albeit we observed a trend pointing at a minor protective effect of a low number of inhibitory KIR/KIR-ligand pairs. The results suggest that the KIR/KIR-ligand genotype has no effect on the susceptibility for the development of de novo AML. |
Membrane bending and sphingomyelinase associated sulfatide dependent hypoxic adhesion of sickle mature erythrocytes. These results suggest that lipid components of the plasma membrane contribute to the complications in SCD. Therefore, sulfatide and the components of its upregulation pathway, particularly sphingomyelinase should be further explored as potential therapeutic targets to inhibit sickle erythrocyte adhesion. |
Outcomes of Breakthrough COVID-19 Infections in Patients with Hematologic Malignancies. In conclusion, COVID-19 vaccination status in patients with hematologic malignancies was associated with a decreased risk of hospitalization but not associated with a decreased risk of death from COVID-19 infections in the pre-Omicron era. Protective strategies, in addition to immunization, are warranted in this vulnerable patient population. |
SAMHD1 Single Nucleotide Polymorphisms Impact Outcome in Children with Newly Diagnosed Acute Myeloid Leukemia. In multivariable analysis, adjusting for other prognostic factors such as race, age, risk group, and white blood cell count, al the SNPs remained independent predictors of clinical outcome endpoints. These results highlight the relevance of the SAMHD1 pharmacogenomics in context of response to Ara-C in AML and warrants the need for further validation in expanded patient cohorts. |
T-replete cord transplants give superior outcomes in high risk and relapsed/refractory paediatric myeloid malignancy. The effect appeared similar regardless of MRD status, (interaction p-value= 0.29). CB transplant without serotherapy may be the optimal transplant option for children with myeloid malignancy. |
| Blood Cancer J |
Alterations of cohesin complex genes in acute myeloid leukemia: differential co-mutations, clinical presentation and impact on outcome. However, we found almost complete mutual exclusivity of genetic alterations of individual cohesin subunits. This mutual exclusivity may be the basis for therapeutic strategies via synthetic lethality in cohesin mutated AML. |
Alternative splicing in multiple myeloma is associated with the non-homologous end joining pathway. We therefore identify an axis of high-risk disease encompassing expression of the non-homologous end joining pathway, increase structural variants, and increased alternative splicing that are linked together. This indicates a joint pathogenic role for DNA damage response and alternative RNA processing in myeloma. |
The management of light chain (AL) amyloidosis in Europe: clinical characteristics, treatment patterns, and efficacy outcomes between 2004 and 2018. There was a significant improvement for stage IIIa (14.2 vs 30.7 months, p = 0.0170) but no improvement for stage IIIb patients (5.0 vs 4.5 months). This European real-world study of AL-amyloidosis emphasizes the unmet needs of early diagnosis, and the lack of improvement in survival outcomes of the frail stage IIIb population, despite the introduction of new therapies in recent years. |
| Haematologica |
Comprehensive in silico and functional studies for classification of EPAS1/HIF2A genetic variants identified in patients with erythrocytosis. Notably, we identified patients with only erythrocytosis associated with germline mutations A530S and Y532C previously identified at somatic state in tumors, thereby raising the complexity of the genotype/phenotype correlations. Altogether, this study allows accurate clinical follow-up of patients and opens the possibility of benefiting from HIF-222inhibitor treatment, so far the only targeted treatment in hypoxia-related erythrocytosis disease. |
Differential inhibition of T cell receptor and STAT5 signalling pathways determines the immunomodulatory effects of dasatinib in chronic phase chronic myeloid leukemia. Finally, patients on other TKI had significantly increased TCR signalling in TIM3+ cells compared to patients taking dasatinib, suggesting that chronic SRC kinase inhibition by dasatinib may play a role in preventing TIM-3 mediated T cell exhaustion and preserve anti-tumour immunity. These data provide further insight into the selective immunomodulatory effects of dasatinib and its potential use for pharmacologic control of immunotherapies. |
Duality of Nrf2 in iron-overload cardiomyopathy. We describe the dual role of Nrf2 when aging is combined with ironoverload and its novel interrelation with UPR system to ensure cell survival. We open new perspective for early and intense treatment of cardiomyopathy in patients with ß- thalassemia before the appearance of heart iron accumulation. |
How we manage cardiovascular disease in patients with hemophilia. Because evidence from clinical trials is lacking, the management of PWH with cardiovascular diseases is mostly based on expert opinions, personal experiences and the adaptation of the evidence stemming from studies on people without hemophilia. In this article, we focus on how to manage coronary artery disease and atrial fibrillation. |
The IgG-degrading enzyme, Imlifidase, restores the therapeutic activity of FVIII in inhibitor-positive hemophilia A mice. In HA mice passively immunized with recombinant human anti-FVIII IgG, IdeS restored the hemostatic efficacy of FVIII, as evidenced by the correction of the bleeding tendency. Our results provide the proof of concept for the transient removal of FVIII inhibitors by IdeS, thereby opening a therapeutic window for efficient FVIII replacement therapy in inhibitor-positive patients. |
The immunomodulatory molecule TIGIT is expressed by chronic lymphocytic leukemia cells and contributes to anergy. Lastly, cells from Richter syndrome patients were characterized by high levels of CD226, with low to undetectable TIGIT, in keeping with their high proliferative drive. Together, these data suggest that TIGIT contributes to CLL anergy by downregulating BCR signaling, identifying novel and actionable molecular circuits regulating anergy and modulating CLL cell functions. |
The relative importance of platelet integrins in hemostasis, thrombosis and beyond. This outside-in signal ensures platelet adhesion, shape change, granule secretion and aggregation. In this review, we examine the role of each platelet integrin in hemostatic plug formation, hemostasis and arterial thrombosis and also beyond these classical functions, notably in tumor metastasis and sepsis. |
Therapeutic potential of fetal liver cells transplantation in hemophilia A mice. Finally, none of the transplanted mice developed anti-FVIII antibodies. Overall, this study sheds some light on the therapeutic potential of healthy FL cells in the cure of HA neonatal/pediatric patients. |
Tislelizumab with gemcitabine and oxaliplatin in patients with relapsed or refractory classic Hodgkin lymphoma: a multicenter phase II trial. Overall, T-GemOx demonstrated promising antitumor activity with manageable toxicities as a salvage treatment for R/R cHL. A longer follow-up duration is required to determine whether maintenance therapy with tislelizumab rather than transplantation can be curative following such a highly active regimen. |
Venetoclax and dinaciclib elicit synergistic preclinical efficacy against hypodiploid acute lymphoblastic leukemia. This combination eradicated leukemic blasts within hypodiploid ALL PDX mice with low off-target toxicity. Our findings suggest that dual inhibition of BCL-2 (venetoclax) and CDK9/MCL-1 (dinaciclib) is a promising therapeutic approach in hypodiploid ALL, warranting further investigation to inform clinical trials in this high-risk patient population. |
| J Hematol Oncol |
A pH-dependent anti-CD47 antibody that selectively targets solid tumors and improves therapeutic efficacy and safety. Our study illustrates that the development of a tumor-selective, pH-dependent anti-CD47 antibody safely confers strong therapeutic effects against solid tumors, thus providing a promising therapeutic strategy to overcome the challenges of anti-CD47 therapy. |
Novel CD19-specific CD19-specific |
| Lancet Haematol |
The effect of granulocyte-colony stimulating factor, decitabine, and busulfan-cyclophosphamide versus busulfan-cyclophosphamide conditioning on relapse in patients with myelodysplastic syndrome or secondary acute myeloid leukaemia evolving from myelodysplastic syndrome undergoing allogeneic haematopoietic stem-cell transplantation: an open-label, multicentre, randomised, phase 3 trial. Funding None. Translation For the Chinese translation of the abstract see Supplementary Materials section. |
| Leukemia |
BET inhibitors rescue anti-PD1 resistance by enhancing TCF7 accessibility in leukemia-derived terminally exhausted CD8+ T cells. BETi synergized with anti-PD1 in vivo, resulting in the reduction of circulating leukemia cells, enrichment of CD8+ T cells in the bone marrow, and increase in expression of Tcf7, Slamf6, and Cxcr5 in CD8+ T cells. Finally, we profiled the epigenomes of in vivo JQ1-treated AML-derived CD8+ T cells by single-cell ATAC-seq and found that JQ1 increases Tcf7 accessibility specifically in Tex cells, suggesting that BETi likely acts mechanistically by relieving repression of progenitor programs in Tex CD8+ T cells and maintaining a pool of anti-PD1 responsive CD8+ T cells. |
Chronic lymphocytic leukemia presence impairs antigen-specific CD8+ T-cell responses through epigenetic reprogramming towards short-lived effectors. Secondary challenge in vivo confirmed dysfunctional memory responses by antigen-experienced OT-I cells generated in presence of CLL. Altogether, we show that presence of CLL induces a short-lived effector phenotype and impaired memory responses by epigenetic reprogramming during primary responses. |
Disruption to the FOXO-PRDM1 axis resulting from deletions of chromosome 6 in acute lymphoblastic leukaemia. We relate this FOXO3-specific leukaemia-protective role to suppression of glycolysis based on integrated analysis of CRISPR-data and gene sets induced or suppressed by FOXO1 and FOXO3. Pan-FOXO agonist Selinexor induced the glycolysis inhibitor TXNIP and suppressed B-ALL growth at low dose (ID < 50 nM). |
Romidepsin-CHOEP followed by high-dose chemotherapy and stem-cell transplantation in untreated Peripheral T-Cell Lymphoma: results of the PTCL13 phase Ib/II study. The primary endpoint was not met; therefore, the enrollment was stopped at a planned interim analysis. The addition of romidepsin to CHOEP did not improve the PFS of untreated PTCL patients. |
Whole genome sequencing provides comprehensive genetic testing in childhood B-cell acute lymphoblastic leukaemia. Our novel bioinformatic pipeline improved detection of DUX4 rearrangements (DUX4-r): a good-risk B-ALL subtype with high survival rates. Overall, we have validated that WGS provides a standalone, reliable genetic test to detect al subtype-defining genetic abnormalities in B-ALL, accurately classifying patients for the risk-directed treatment stratification, while simultaneously performing as a research tool to identify novel disease biomarkers. |
| Thromb Haemost |
Bleeding Risk in Elderly Patients with Venous Thromboembolism Who Would Have Been Excluded from Anticoagulation Trials. The bleeding risk increases significantly with the number of exclusion criteria present. Thus, results from such trials may not be generalizable to older, multimorbid, and co-medicated patients. |
Incidence of Pregnancy-associated Venous Thromboembolism: Second Nationwide Study. Advanced maternal age, Cesarean section, multiparity, and multifetal pregnancies increased the risk of PA-VTE. Obstetricians need to be cautious of VTE, particularly during the postpartum period, in high-risk pregnant patients. |
Multiallelic Copy Number Variation in ORM1 is Associated with Plasma Cell-Free DNA Levels as an Intermediate Phenotype for Venous Thromboembolism. Therefore, the genetic basis of NETs could reveal novel risk factors for VTE. A recent genome-wide association study of plasma cell-free DNA (cfDNA) levels in the Genetic Analysis of Idiopathic Thrombophilia 2 (GAIT-2) Project showed a significant associated locus near appears to be a novel marker for cfDNA levels, which could contribute to VTE risk. |
Recurrent thrombosis and bleeding in patients with cancer associated VTE receiving anticoagulation: are these modifiable risk factors for mortality? Patients with cancer associated venous thromboembolism (VTE) have a higher risk of recurrent VTE than those without cancer and require long-term anticoagulation, but these patients are also at higher risk of anticoagulant-related bleeding because of the frequent presence of disease- or treatment-related predispositions for bleeding. |
Plenty of the editorials are available as full text through the publisher website using the provided link
| Am J Hematol |
Complement biology for hematologists. The availability of a rapidly growing number of innovative complement inhibitors has opened new therapeutic perspectives for several other hematological disorders in which the complement is involved at different degrees. This review focuses on complement biology and its mechanisms of activation in hematological diseases. |
Sequencing Antigen-Targeting Antibodies and Cellular Therapies in Adults With Relapsed/Refractory B-Cell Acute Lymphoblastic Leukemia. These therapies can be complementary and used either sequentially or concomitantly. Here, we review the current landscape of antigen-targeted therapies for r/r B-ALL and discuss considerations for their use. |
| Ann Oncol |
| Blood |
Spotlight on vaccine-induced thrombosis and thrombocytopenia (VITT). Similarities between this syndrome, vaccine-induced thrombocytopenia and thrombosis (VITT), and heparin-induced thrombocytopenia, prompted recognition of the role of anti-platelet factor 4 (PF4) antibodies and management strategies based on intravenous immunoglobulin and non-heparin anticoagulants, which improved outcome. We update current understanding of VITT and potential involvement of anti-PF4 antibodies in thrombotic disorders. |
| J Hematol Oncol |
How we treat primary immune thrombocytopenia in adults. An optimized treatment strategy should aim at elevating the platelet counts to a safety level with minimal toxicity and improving patient health-related quality of life, and always needs to be tailored to the patients and disease phases. In this review, we address the concepts of adult ITP diagnosis and management and provide a comprehensive overview of current therapeutic strategies under general and specific situations. |
Payload diversification: a key step in the development of antibody-drug conjugates. Among future developments in the ADC field, payload diversification is expected to play a key role as illustrated by a growing number of preclinical and clinical stage unconventional payload-conjugated ADCs. This review presents a comprehensive overview of validated, forgotten and newly developed payloads with different mechanisms of action. |
Protein degradation: expanding the toolbox to restrain cancer drug resistance. We also highlight specific E3 ligases, DUBs, and chaperones, discussing possible strategies modulating protein degradation to target cancer drug resistance. A systematic summary of the molecular basis by which protein degradation regulates tumor drug resistance will help facilitate the development of appropriate clinical strategies. |
misc publications eg case reports, tools of the trade, images of the month, etc…
| Am J Hematol |
| Blood |
| Blood Adv |
| Lancet Haematol |
| Leukemia |
| Thromb Haemost |
Letters to the editors and authors’ replies
| Am J Hematol |
| Ann Oncol |
| Blood Cancer J |
| Leukemia |