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- 256 - Stamping out high-risk myeloma with D-KRd and tandem transplant; plasmin-cleaved VWF in microthrombosis; SCD plasma sensitizes iPSC-derived sensory neurons
In this week's podcast we'll discuss another step forward in stamping out high-risk myeloma. Then we'll hear about the plasmin-cleaved von Willebrand factor, or VWF, in microthrombosis. Finally we'll hear about new insights into the origins of sickle cell pain.
Featured Articles:
Daratumumab, carfilzomib, lenalidomide, and dexamethasone with tandem transplant for high-risk newly
diagnosed myelomaPlasmin-cleaved von Willebrand factor as a biomarker for microvascular thrombosisSickle cell disease iPSC-derived sensory neurons exhibit increased excitability and sensitization to patient
plasmaThu, 16 May 2024 - 255 - Allogeneic transplant in first remission for post-induction molecular MRD; circulating HSPCs actively participate in human hematopoiesis; let-7 miRNAs repress HIC2 to regulate BCL11A transcription and hemoglobin switching
In this week's episode we’ll discuss the utility of MRD in identifying patients with NPM1 AML who benefit from allogeneic transplant in first remission, learn more about the contribution of circulating hematopoietic stem/progenitor cell subsets to human hematopoietic hemostasis, and discuss the role of Let-7 miRNAs in regulation of BCL11A transcription and hemoglobin switching.
Featured Articles:
Postinduction molecular MRD identifies patients with NPM1 AML who benefit from allogeneic transplant in first remissionlet-7 miRNAs repress HIC2 to regulate BCL11A transcription and hemoglobin switching Circulating Hematopoietic Stem/Progenitor Cell subsets contribute to human hematopoietic homeostasisThu, 09 May 2024 - 254 - ADAMTS13 recovery in caplacizumab-treated TTP; inhibition of venetoclax-resistant BCL2 variants with sonrotoclax; genomic insights from Castleman disease in twins
In this week's epside we'll learn about ADAMTS recovery after caplacizumab therapy in patients with immune thrombotic thrombocytopenic purpura. Then, we'll hear about preclinical characterization of sonrotoclax, a potential second-generation BCL2 inhibitor. Finally we'll hear about new insights into the etiology of Castleman disease where researchers describe the unusual occurrence of idiopathic multicentric Castleman disease in identical twins.
Featured Articles:
ADAMTS13 recovery in acute thrombotic thrombocytopenic purpura after caplacizumab therapySonrotoclax overcomes BCL2 G101V mutation–induced venetoclax resistance in preclinical models of
hematologic malignancySingle-cell landscape of idiopathic multicentric Castleman disease in identical twinsThu, 02 May 2024 - 253 - Durable response after tisa-cel in adults with relapsed/refractory follicular lymphoma; high microRNA-145 plasma levels indicate decreased risk of VTE; epigenetic/immunogenetic signature in the prediction of outcomes for high-count monoclonal B lymphocyto
In this week's episode, we’ll discuss the findings from a study assessing responses after treatment with tisagenlecleucel [LM1] in adults with relapsed/refractory follicular lymphoma, learn more about the association between high microRNA-145 plasma levels and decreased risk of future incident venous thromboembolism, and discuss how epigenetic and immunogenetic signatures can be used in the prediction of outcomes for high-count monoclonal B lymphocytosis.
Durable Response After Tisagenlecleucel in Adults With Relapsed/Refractory Follicular Lymphoma: ELARA Trial Update Prediction of outcomes for high-count monoclonal B lymphocytosis using an epigenetic and immunogenetic signature High microRNA-145 plasma levels are associated with decreased risk of future incident venous thromboembolism: The HUNT study
Featured Articles:Thu, 25 Apr 2024 - 252 - Gut microbiota exploitation by CPX-351 in AML; optimizing anti-myeloma immunity for ASCT; which pediatric ITP patients will develop lupus?
In this week's episode, we'll discuss gut microbiota exploitation by CPX-351 in acute myeloid leukemia. Then we'll learn about optimizing anti-myeloma immunity. New research shows that regulatory T cells suppress myeloma-specific immunity during autologous stem cell mobilization and transplantation. Finally we'll discuss among pediatric patients with ITP or other autoimmune cytopenias, which ones will go on to develop systemic lupus?
Featured Articles:
CPX-351 exploits the gut microbiota to promote mucosal barrier function, colonization resistance, and immune homeostasisRegulatory T cells suppress myeloma-specific immunity during autologous stem cell mobilization and transplantationAntinuclear antibody–associated autoimmune cytopenia in childhood is a risk factor for systemic lupus erythematosusThu, 18 Apr 2024 - 251 - Jak2V617F clonal hematopoiesis promotes arterial thrombosis; Staphylococcus aureus infection in Sézary syndrome; clinical features of RAC2-related immunodeficiency
In this week's episode we’ll discuss the mechanism by which Jak2V617F clonal hematopoiesis promotes arterial thrombosis, discuss how Staphylococcus aureus induces drug resistance in cancer T cells in Sézary syndrome, and learn more about the clinical and functional features of RAC2-related immunodeficiency.
Featured Articles:
Jak2V617F clonal hematopoiesis promotes arterial thrombosis via platelet activation and cross talkStaphylococcus aureus induces drug resistance in cancer T cells in Sézary syndromeClinical and functional spectrum of RAC2-related immunodeficiencySat, 13 Apr 2024 - 250 - Molecular mimicry in aplastic anemia; emicizumab prophylaxis in infants with hemophilia; hydroxyurea reduces infections in SCA
In this week's episode we'll discuss molecular mimicry in aplastic anemia, novel experiments show that antigens associated with viral infections can mimic epitopes presented on hematopoietic progenitor cells. Then, we'll learn about prophylaxis with subcutaneous emicizumab in infants with hemophilia. Finally we'll see how hydroxyurea is associated with a significant reduction in infections among children with sickle cell anemia in Uganda.
Articles featured this week:
Virus-reactive T cells expanded in aplastic anemia eliminate hematopoietic progenitor cells by molecular
mimicryEmicizumab prophylaxis in infants with hemophilia A (HAVEN 7): primary analysis of a phase 3b open-label
trialHydroxyurea reduces infections in children with sickle cell anemia in UgandaThu, 04 Apr 2024 - 249 - Review Series on the Influence of the Tumor Microenvironment on the Pathogenesis of B-Cell Lymphomas
In this bonus episode of Blood Podcast, Associate Editor, Dr. Freda Stevenson is joined by Drs. Karin Tarte, Andrea Radtke, and Leandro Cerchietti to discuss the Review Series on the influence of the tumor microenvironment on the pathogenesis of B-cell lymphomas.
Find the full review series in Blood Journal volume 143 issue 12.
Thu, 28 Mar 2024 - 248 - Free light chain mass spectrometry in diagnosis and monitoring of AL amyloidosis; T cells of AML patients in remission have distinct RNA signatures; and protective effect of ADAMTS13 in sickle cell mice depends on von Willebrand factor clearance
In this week's episode we’ll discuss the findings from a study assessing the utility of free light chain mass spectrometry in AL amyloidosis, learn more about distinct single-cell RNA-sequencing signatures of bone marrow T cells of AML patients in remission after an allogeneic stem cell transplant, and discuss why von Willebrand factor clearance is critical for the protective effect of ADAMTS13 in mice with sickle cell anemia.
Articles featured in this episode:
Clearance of VWF by hepatic macrophages is critical for the protective effect of ADAMTS13 in sickle cell anemia mice Complete responses in AL amyloidosis are unequal: the impact of free light chain mass spectrometry in AL amyloidosisThe remission status of patients with AML post-alloSCT is associated with a distinct single-cell bone marrow T-cell signatureThu, 28 Mar 2024 - 247 - Eculizumab in transplant-associated thrombotic microangiopathy; reclassifying malignant monocytosis; targeting tissue factor in antiphospholipid syndrome
In this week's episode we'll discuss eculizumab in stem cell transplant-associated thrombotic microangiopathy. Then, we'll learn about reclassifying malignant monocytosis, these newly classified cases have distinct mutational and transcriptional profiles. Finally, we'll hear about targeting the tissue factor coagulation initiation complex prevents antiphospholipid antibody development.
Articles featured in this episode:
A prospective multi-institutional study of eculizumab to treat high-risk stem cell transplantation–associated TMA Comparing malignant monocytosis across the updated WHO and ICC classifications of 2022 Treatment outcomes of complement protein C5 inhibition in 509 UK patients with paroxysmal nocturnal hemoglobinuriaThu, 21 Mar 2024 - 246 - Identification of rare relapse-initiating stem cells post-transplantation; interferon α impairs erythropoiesis in sickle cell disease; TNFα promotes clonal dominance of KIT D816V+ cells in mastocytosis
In this week's episode we’ll learn more about rare relapse-initiating stem cells in patients with MDS or AML in complete remission post-transplantation, discuss the role of interferon α in erythropoiesis in sickle cell disease, and learn more about how TNFα promotes clonal dominance of KIT D816V+ cells in mastocytosis.
Thu, 14 Mar 2024 - 245 - How PAR2 signaling drives thrombo-inflammation; pretransfusion hemoglobin levels linked to survival in beta-thalassemia; etoposide is better than its reputation in primary HLH
In this week's episode we'll discuss PAR2-biased signaling in thrombo-inflammation. Then, we'll learn about how hemoglobin levels are linked to survival in transfusion-dependent beta-thalassemia. Finally we'll hear about how etoposide is better than its reputation in primary HLH—hemophagocytic lymphohistiocytosis. Symptomatic patients treated with etoposide have substantially better outcomes as compared to the historical experience.
Thu, 07 Mar 2024 - 244 - Brentuximab vedotin plus dacarbazine or nivolumab in classical Hodgkin lymphoma; loss of CD20 causes resistance to mosunetuzumab in r/r B-cell lymphomas; trogocytosis as a driver of RBC antigen loss
In this week's episode we’ll discuss the findings from a prospective trial of brentuximab vedotin with dacarbazine or nivolumab in older patients with classical Hodgkin lymphoma, learn more about CD20 antigen loss as a mechanism of resistance to mosunetuzumab in relapsed/refractory B-cell lymphomas, and discuss the role of trogocytosis in red blood cell antigen loss.
Thu, 29 Feb 2024 - 243 - CAR T cells plus ibrutinib in relapsed/refractory MCL; targeting SGF29 in AML; diffusion-limited oxygen release from stored blood
In this week's episode we'll discuss CAR T cells plus ibrutinib for the treatment of relapsed/refractory mantle cell lymphoma. Next, we'll learn about a new SAGA for acute myeloid leukemia. Finally, we'll hear about new evidence that oxygen delivery to tissues can become diffusion-limited during perfusion with stored blood.
Thu, 22 Feb 2024 - 242 - Long-term outcomes of pulmonary embolism in children and adolescents; hereditary angioedema caused by a methionine-379 to lysine substitution in kininogens; predictors of loss of MRD negativity in multiple myeloma
In this week's episode we’ll report on the findings from a study evaluating the long-term outcomes of pulmonary embolism in children and adolescents, discuss a new mechanism for hereditary angioedema caused by a methionine-379 to lysine substitution in kininogens, and learn more about predictors of unsustained minimal residual disease negativity in multiple myeloma patients.
Thu, 15 Feb 2024 - 241 - Extended follow-up of axi-cel in indolent NHL; platelets help clear senescent RBCs; novel risk stratification strategy for CNS lymphoma
In this week's episode we'll discuss extended follow-up from the ZUMA-5 trial of axicabtagene ciloleucel, or axi-cel. Then we'll learn about the role of platelets in binding and clearing senescent red blood cells. Finally, we'll hear about a new risk stratification strategy for lymphomas of the central nervous system, or CNS.
Thu, 08 Feb 2024 - 240 - Lisocabtagene maraleucel in relapsed or refractory large B-cell lymphoma; reciprocal stabilization of coagulation factor XIII-A and -B subunits; inotuzumab ozogamicin for MRD in ALL
In this week's episode we’ll discuss the findings from a two-year follow-up study of lisocabtagene maraleucel in relapsed or refractory large B-cell lymphoma, learn more about how reciprocal stabilization of coagulation factor XIII-A and -B subunits influences plasma FXIII concentration, and discuss the findings from a phase 2 study of inotuzumab ozogamicin for measurable residual disease in acute lymphoblastic leukemia in remission.
Thu, 01 Feb 2024 - 239 - Maternal anticancer drug exposure and leukemia; PIEZO1-TMEM16F coupling in hereditary xerocytosis; NPM1 MRD during venetoclax therapy in NPM1-mutated AML
In this week’s episode, we’ll discuss the association between occupational exposure to anticancer agents in a parent and subsequent cancer in a child. Then we’ll learn about deciphering and disrupting the activation of PIEZO1 in hereditary xerocytosis. Finally, we’ll hear about the assessment of measurable residual disease, or MRD, in patients with NPM1-mutated AML, or acute myeloid leukemia, receiving venetoclax-based NON-intensive therapy.
Thu, 25 Jan 2024 - 238 - TCRαβ/CD19-cell depleted haploHSCT for pediatric leukemia; malignancy-associated hemophagocytic lymphohistiocytosis in Sweden; the bone marrow as the primary site of thrombopoiesis
In this week's episode we’ll discuss the findings from a prospective trial of TCRαβ/CD19-cell depleted HLA-haploidentical transplantation to treat pediatric acute leukemia, learn more about the incidence, clinical characteristics, and survival of malignancy-associated hemophagocytic lymphohistiocytosis in Sweden, and discuss the bone marrow as the primary site of thrombopoiesis.
Thu, 18 Jan 2024 - 237 - Fibrin polymerization and thrombosis; preventing CD19-negative relapse after CAR T-cell therapy in ALL; and impact of aberrant FUS condensates on HSC aging
In this week's episode we’ll explore the role of fibrinogen polymerization in thrombosis. Then, we’ll discuss preventing CD19-negative relapse after CAR T-cell therapy in acute lymphoblastic leukemia. Finally, we’ll learn how increased levels of the RNA-binding protein FUS has been identified as an effector of hematopoietic stem cell aging.
Thu, 11 Jan 2024 - 236 - CD24Fc for prevention of GVHD; origins of active EBV disease; the role of PF4 in platelet activationThu, 04 Jan 2024
- 235 - Profiling a new VITT-like disorder; real-world outcomes of tafasitamab and lenalidomide in LBCL; and spatial mapping of human hematopoiesis
In this week's episode we'll uncover the clinical and pathological profile of a new disorder similar to VITT, or vaccine-induced thrombocytopenia and thrombosis. Then, we'll discuss real-world outcomes in patients with large B-cell lymphoma treated with tafasitamab and lenalidomide. Finally we'll learn about how advances in technology help unravel the spatial biology of bone marrow.
Thu, 28 Dec 2023 - 234 - A natural history of familial platelet disorder with myeloid malignancy; HEXIM1 as an essential transcription regulator in erythropoiesis; residual disease predicts relapse in CML patients
In this week's episode we’ll discuss the findings from a natural history study of patients with familial platelet disorder with myeloid malignancy, learn more about the role of HEXIM1 as an essential transcription regulator in human erythropoiesis, and discuss the utility of residual disease as a predictor of relapse in CML patients stopping TKI therapy.
Thu, 21 Dec 2023 - 233 - ETP and MRD for risk assessment in T-ALL; allogeneic HCT outcomes in CGD; effects of pathogenic/likely pathogenic variants in inherited hemostasis disordersThu, 14 Dec 2023
- 232 - Sorafenib plus intensive chemotherapy in newly diagnosed FLT3-ITD AML; inhibition of PLK4 in TP53-mutated AML; the role of CD44 in Plasmodium falciparum infectionThu, 07 Dec 2023
- 231 - High-risk cytogenetics in solitary bone plasmacytomas; complement activation in vaso-occlusive pain episodes; platelet reactivity to predict thrombotic disease risk
On today’s podcast we'll discuss high-risk cytogenetic abnormalities in solitary bone plasmacytomas. Then, we'll consider complement activation in vaso-occlusive pain episodes and how targeting C5a generation inhibited those effects. Finally we'll explore the genetics of platelet reactivity and how researchers used this data to develop a genetic score that was associated with risk of thrombotic diseases.
Thu, 30 Nov 2023 - 230 - Very long-term follow-up of FCR therapy for CLL, risk assessment of KMT2A-rearranged B-cell precursor ALL in adults; anti-myeloma therapy using antibodies armed with B-BiTEs
On this week's episode we’ll discuss the findings from a long-term follow up study of fludarabine, cyclophosphamide, and rituximab in IGHV-mutated CLL, learn more about the impact of genetic alterations and minimal residual disease in adults with KMT2A-rearranged B-cell precursor ALL, and discuss a pre-clinical study of reinforced immunotherapy for myeloma using a new bispecific antibody-based approach.
Thu, 23 Nov 2023 - 229 - Fractionated gemtuzumab ozagamicin Dosing in Elderly AML Patients; Loss-of-function of ENT3 drives histiocytosis; Alternative splicing of CD20 5’-UTR in B-lymphomas
In this week's episode we'll discuss if fractionated dosing of gemtuzumab ozogamicin provide additional benefit over a single dose in older adults with AML. Then, we'll consider how the loss-of-function of ENT3 drives histiocytosis. Researchers describe a novel pathway leading to histiocytosis that involves hyperactivation of TLR-MAPKinase signaling. This suggests a potential benefit of MAPKinase -directed targeted therapy in a range of histocytoses. Finally we'll discuss unraveling resistance mechanisms to anti-CD20 treatments in B-cell malignancies. Through alternative splicing, the MS4A1 gene encoding human CD20 generates multiple mRNA isoforms with distinct 5’ untranslated regions.
Thu, 16 Nov 2023 - 228 - Review Series on RNA Therapeutics in Hematology
In this bonus episode of Blood Podcast, Coordinating Editor, Dr. Jason Gotlib is joined by Drs. Sioban Keel, Margaret Ragni, and Andoni Echaniz-Laguna to discuss the Review Series on RNA Therapeutics in Hematology. The series highlights areas in which RNA therapeutics are most advanced: acute hepatic porphyria, transthyretin amyloidosis, and hemophilia.
Tue, 14 Nov 2023 - 227 - Prognostic significance of splicing factor gene mutations in AML; therapy resistance in multiple myeloma; the effects of KIT ligand deletion on HSC homeostasis
In this week's episode we’ll discuss the prognostic significance of splicing factor gene mutations in newly diagnosed AML, learn more about the findings from a multi-omics study of therapy resistance in multiple myeloma, and discuss the effects of KIT ligand deletion on systemic KIT levels and hematopoietic stem cell homeostasis.
Thu, 09 Nov 2023 - 226 - Targeting prostacyclin to inhibit platelet activation; MRD-tailored myeloma maintenance; AREG and HSC function in DNA damage repair deficiency and aging
In this week's episode we'll see how targeting the prostacyclin receptor is a promising strategy for regulating hemostasis and thrombosis. Then, we'll learn how new evidence indicates that the progression rate is low in MRD-negative myeloma patients who discontinue post-transplant lenalidomide and dexamethasone maintenance therapy after 2 years. Finally we'll discuss how amphiregulin from leptin receptor-positive niche cells in the bone marrow mediates crosstalk between the niche and hematopoietic stem cells under conditions of DNA repair deficiency and aging.
Thu, 02 Nov 2023 - 225 - Lenalinomide plus rituximab for elderly patients with DLBCL, platelet GP6-mediated neutrophil recruitment in acute lung injury, and the role of AXL3 in mantle cell lymphoma.
In this week's episode, we discuss the findings from a phase 2 study of lenalinomide plus rituximab in elderly frail patients with DLBCL, learn more about platelet GP6-mediated neutrophil recruitment in early stages of acute lung injury, and discuss a newly identified isoform of the tyrosine kinase AXL, termed AXL3, in mantle cell lymphoma.
Thu, 26 Oct 2023 - 224 - Gut microbiota diversity and mortality in pediatric allo-HSCT; C5 inhibition in atypical HUS; and pembrolizumab plus vorinostat in PD-1-refractory Hodgkin lymphoma
In this week's episode, we'll learn how the diversity of gut microbiota predicts mortality and acute graft-versus-host disease in pediatric allogeneic transplant recipients. Then we'll discuss complement inhibition in patients with complement-mediated atypical hemolytic uremic syndrome. Finally we'll learn how PD-1 plus HDAC equals responses in previously treated Hodgkin lymphoma, specifically that response rates were encouraging in a heavily pretreated cohort, even among patients with PD-1 refractory disease.
Thu, 19 Oct 2023 - 223 - IL-15 inhibitor BNZ-1 is safe and effective in T-cell LGLL, gene therapy trial for Wiskott-Aldrich syndrome, and ethical framework to select patients for CAR T-cell therapy
In this week's episode, we’ll discuss a phase two trial in patients with T-cell large granular lymphocytic leukemia treated with the inhibitor BNZ-1 to block receptor binding of IL-15, learn more about the outcomes of gene therapy for Wiskott-Aldrich syndrome, and discuss ways to mitigate inequity when prioritizing patients for CAR T-cell therapy.
Thu, 12 Oct 2023 - 222 - DDX41 gene variant prevalence and AML/MDS risk, VITAL mAb treatment of light chain amyloidosis, and movement/neurocognitive toxicities after BCMA CAR T cell treatment
In this week’s episode, we’ll learn that Germline pathogenic variants of the DDX41 gene are relatively common in the general population and linked to higher risk of AML and MDS, discuss the birtamimab plus standard of care in light chain amyloidosis, and review new insights on rare movement and neurocognitive toxicities that are observed after BCMA-directed CAR T cell treatment.
Thu, 05 Oct 2023 - 221 - IL-7 receptor signaling in B-cell differentiation, venetoclax plus obinutuzumab in older patients with CLL, LDL promotes microvascular thrombosis via von Willebrand Factor
In this weeks episode, we’ll learn more about the role of IL-7 receptor signaling in the differentiation and expansion of human B-cell progenitors, discuss the use of fixed-duration venetoclax plus obinutuzumab in older patients with chronic lymphocytic leukemia, and learn how low-density lipoprotein promotes microvascular thrombosis by enhancing von Willebrand Factor self-association
Thu, 28 Sep 2023 - 220 - Real-world CAR T therapy in older DLBCL patients, monoclonal antibody blocking APC for hemophilia therapy, and targeting the epichaperome in AMLThu, 21 Sep 2023
- 219 - Obinutuzumab, ibrutinib, and venetoclax in untreated CLL with deletion(17p)/TP53 mutation; NOTCH2 mutants promote chemo-resistance in DLBCL; and the role of DBY/HLA class II complexes in chronic GVHDThu, 14 Sep 2023
- 218 - Long-term outcomes with pembrolizumab in Hodgkin lymphoma, the “incredible ULK” alleviates β-thalassemia, and recommendations for managing CAR T hematotoxicityThu, 07 Sep 2023
- 217 - How I Manage Inpatient Consultations for Quantitative Neutrophil Abnormalities in AdultsThu, 31 Aug 2023
- 216 - Dimethyl fumarate in cutaneous T-cell lymphoma, lipid nanoparticles for editing of human hematopoietic cells, and racial and geographic disparities in lymphoma trials
In this week's episode, we’ll learn more about the treatment of relapsed and refractory cutaneous T-cell lymphoma with dimethyl fumarate, discuss the use of lipid nanoparticles for ex vivoediting of human hematopoietic cells, and learn more about racial and geographic disparities in lymphoma clinical trials.
Thu, 31 Aug 2023 - 215 - Detailed safety profile of acalabrutinib vs ibrutinib in CLL, inflammation in trauma-induced coagulopathy, abatacept exposure and acute GVHD risk
In this week’s episode, we’ll review a detailed safety profile of acalabrutinib versus ibrutinib in patients with previously treated chronic lymphocytic leukemia, discuss a report that leukocyte inflammation contributes to trauma-induced coagulopathy by oxidation and degradation of fibrinogen, and finally, discuss a pharmacokinetic-pharmacodynamic analysis that shows higher abatacept exposure decreases occurrence of acute graft versus host disease (GVHD) after allogeneic hematopoietic stem cell transplantation (HSCT) from an unrelated donor.
Thu, 24 Aug 2023 - 214 - Pembrolizumab after ASCT in PTCL, germline predisposition to myeloid neoplasms in patients with hypoplastic bone marrow, and limited plasticity of monocyte fate and function
In this week’s episode, we’ll discuss pembrolizumab after autologous stem cell transplantation in patients with peripheral T-cell lymphoma. Newly reported phase 2 study results show that blocking PD-1 with pembrolizumab had a favorable safety profile and demonstrated promising activity, supporting further confirmatory studies in this setting; germline genetic predisposition to myeloid neoplasms in patients with hypoplastic bone marrow. Researchers report mutations that are significantly associated with cytopenias in adulthood in these patients. And pathogenic or likely pathogenic variants were linked to severe cytopenias and advanced myeloid malignancies; and finally, if monocytes and their descendants are less plastic than previously thought. Investigators have identified four functionally specialized monocyte subsets that derive from specific myeloid progenitor lineages. They show that the fate of these monocyte subsets is epigenetically scripted, with little flexibility after differentiation begins, even under conditions of stress.
Thu, 17 Aug 2023 - 213 - Review Series on Hematopoietic Stem CellsThu, 10 Aug 2023
- 212 - WGS informs risk of follicular lymphoma transformation; resolvin D4 regulates neutrophil deployment; Hodgkin lymphoma-directed treatment for early-stage NLPHL
In this week's episode, we’ll learn more about what whole genome sequencing reveals about genetic subtypes of follicular lymphoma and risk of transformation, discuss the role of the lipid mediator, resolvin D4, in infectious neutrophil deployment and emergency granulopoiesis, and learn more about Hodgkin lymphoma-directed therapy and the role of PET in early-stage nodular lymphocyte-predominant Hodgkin lymphoma.
Thu, 10 Aug 2023 - 211 - Ventricular arrhythmias in sickle cell anemia, molecular heterogeneity of pediatric lymphoproliferative disorders, the role of the bone marrow microenvironment in myeloid disorders
In this week's episode, we'll learn more about ventricular arrhythmias in sickle cell anemia, discuss the molecular heterogeneity of pediatric monomorphic post–solid organ transplant lymphoproliferative disorders, and uncover the role of the bone marrow microenvironment as a driver of myeloid disorders.
Thu, 03 Aug 2023 - 210 - Silent infarcts in iTTP remission, a ZDHHC palmitoyltransferase regulates oxidative phosphorylation in AML, and hepatic sinusoid as a niche for ANKL
In this week’s episode, we discuss the impact of silent cerebral infarction in patients with immune mediated thrombotic thrombocytopenic purpura (or iTTP) in clinical remission, how the survival of leukemia stem cells is highly dependent on oxidative phosphorylation in the mitochondria, and targeting iron import as a potential therapeutic approach in aggressive natural killer cell leukemia (or ANKL).
Thu, 27 Jul 2023 - 209 - Poverty and relapse risk in children with ALL, eligibility and enrollment of diverse populations in myeloma trials, and clonal hematopoiesis in VEXAS syndromeThu, 20 Jul 2023
- 208 - Pembrolizumab in PMBCL, allogeneic CD19 CAR T cells for pediatric B-cell ALL, and fetal iron overload in β-thalassemia
In this week's episode, we'll discuss if some patients with relapsed or refractory primary mediastinal B-cell lymphoma can be cured by checkpoint blockade alone. Next, autologous CAR T cells are highly effective, yet not always feasible in children with relapsed or refractory B-cell precursor acute lymphoblastic leukemia. Lastly, we'll discuss ironing out beta-thalassemia during pregnancy.
Thu, 13 Jul 2023 - 207 - Gene therapy for WHIM syndrome, fate of hematopoietic stem cells after transplantation, and the role of C-terminal FGF23 peptides in iron conservationThu, 06 Jul 2023
- 206 - Key role of hepcidin in polycythemia vera, signatures of CAR T cell dysfunction, and IL-34 as a novel AML therapy?
In this week's episode, we'll discuss new evidence on the critical role of hepcidin, the master regulator of iron metabolism, in the pathogenesis of polycythemia vera. Next, costimulatory molecules regulate mechanisms of CAR T cell dysfunction. Finally, we'll discuss how TREM2 is a novel receptor for IL-34, promoting differentiation of normal and leukemic myeloid cells.
Thu, 29 Jun 2023 - 205 - BMT as initial treatment for severe aplastic anemia, macrophage metabolic rewiring in sickle cell disease, and predicting outcomes using PET radiomics in diffuse large B cell lymphoma
In this week’s episode we’ll report on the findings from a phase 2 trial of bone marrow transplantation as initial therapy for patients with severe aplastic anemia, discuss the utility of a PET radiomics-based model in predicting outcomes in diffuse large B-cell lymphoma, and learn more about macrophage metabolic rewiring in sickle cell disease.
Thu, 22 Jun 2023 - 204 - End of the vincristine/steroid pulse era in pediatric ALL?, “trial and error” with abatacept in GVHD, and hemorrhage risk with dasatinib therapy
In this week’s episode we will review no survival benefit for vincristine/steroid pulses in contemporary studies of childhood acute lymphoblastic leukemia (or ALL). Next, the rheumatology drug abatacept may be a promising strategy for the treatment of acute graft-versus-host disease (or GVHD). Finally, we'll discuss the hemorrhage risk of dasatinib therapy.
Thu, 15 Jun 2023 - 203 - Prolonged response after stopping TPO-RA in ITP, TP53 mutations and myelofibrosis outcomes, clinical picture of ERCC6L2 disease, where variants predispose to marrow failure and malignancyThu, 08 Jun 2023
- 202 - Hodgkin lymphoma outcomes in the novel agent era, genomic safe harbors for precision T cell engineering, and a transcriptomic atlas to map imatinib resistance in CML
In this week’s episode, we'll discuss how patients with relapsed or refractory Hodgkin lymphoma survival outcomes have improved after development of several novel agents. Next, precision engineering of therapeutic T cells through extragenic safe harbors. Finally, using a single-cell atlas to map features of imatinib resistance in diagnostic CML bone marrow, investigators present gene expression signatures predictive of response to TKI therapy.
Thu, 01 Jun 2023 - 201 - Pembrolizumab plus AVD for classical Hodgkin lymphoma, targeting the CD40/CD40-ligand axis in Waldenström Macroglobulinemia, and CXCR4-expressing CAR-cytokine induced killer cells in AML
In this week’s episode we’ll discuss the findings from a study exploring the combination of concurrent pembrolizumab, adriamycin, vinblastine, and dacarbazine in newly diagnosed classical Hodgkin lymphoma, learn more about the effects of targeting the CD40/CD40-ligand axis in Waldenström Macroglobulinemia, and review the findings from a study aimed at improving the bone marrow homing of CAR-cytokine induced killer cells in AML.
Thu, 25 May 2023 - 200 - How I Treat Series: Emergent CAR T-Cell ToxicitiesThu, 18 May 2023
- 199 - Specific CD8+ T cell clones in ITP, Refining DLBCL prognosis with the “dark-zone signature”, and rethinking the regenerative role of HSCs in acute hematopoietic emergencies
In this week’s episode, we will review patients with chronic ITP having clonal expansions of a specific subset of CD8 T cells, called terminally differentiated effector memory T cells, or TEMRA. Next, for patients with diffuse large B-cell lymphomas, use of a so-called dark-zone signature, previously referred to as the double-hit signature, could help refine prognosis. Finally on today's podcast we'll discuss rethinking the role of hematopoietic stem cells following physiologic emergencies such as acute inflammation and blood loss.
Thu, 18 May 2023 - 198 - Tips for Trainees for a Career in Publishing with Drs. Nancy Berliner and Andrew Roberts
In this special episode, Trainee Council Chairs, Drs. Becky Zon and Ajay Major, interview Dr. Nancy Berliner, Blood Editor-in Chief and Dr. Andrew Roberts, Blood Deputy Editor, on their careers in academic editing and publishing, including career development tips for trainees who are interested in a career in publishing.
Mon, 15 May 2023 - 197 - Axi-cel in refractory large B-cell lymphoma, effects of C1 inhibitor deficiency on coagulation, and the evolution of therapy-related myeloid neoplasms
In this week’s episode we’ll report on the findings from a 5-year follow-up study of axicabtagene ciloleucel in refractory large B-cell lymphoma, discuss the role of C1 inhibitor deficiency in coagulation and venous thrombosis, and learn how chemotherapy signatures can be used to track the evolution of therapy-related myeloid neoplasms.
Thu, 11 May 2023 - 196 - Gut microbiota and outcomes in DLBCL, NFIA-ETO2 fusion cooperates with TP53 in leukemogenesis, and the impact of nirmatrelvir + ritonavir on CLL patient outcomes during the Omicron surge
In this week’s episode we'll review imbalances in gut microbiota may impact the efficacy and safety of immunochemotherapy in patients with diffuse large B-cell lymphoma. Next, theNFIA-ETO2 fusion, found exclusively in pediatric patients with pure erythroid leukemia, impairs the normal process of erythroid differentiation. Finally, we'll look at the effectiveness of nirmatrelvir plus ritonavir in patients with CLL infected with SARS-CoV-2 during the Omicron surge.
Thu, 04 May 2023 - 195 - Revised response criteria for high-risk MDS, machine learning guides diagnosis of bone marrow failure syndromes, and RhD-positive transfusions for Asian-type DEL patients with serologic RhD-negative typing
In this week’s episode, we’ll discuss the newly revised International Working Group response criteria for patients with higher-risk MDS, learn more about the utility of machine learning in the differential diagnosis of bone marrow failure, and discuss whether patients with the Asian-type DEL allele, who type as serologic Rh-D-negative, can be safely transfused with RhD-positive blood.
Thu, 27 Apr 2023 - 194 - AIHA during pregnancy, rapid immune tolerance induction in severe hemophilia A, and aging changes control of HSC proliferation
In this week’s episode we will review treatment and outcomes for patients with autoimmune hemolytic anemia during pregnancy. Next, rapid immune tolerance induction in patients with hemophilia A and high-titer inhibitors. Finally, researchers compare kinetics and cell cycle progression in hematopoietic stem cells from cord blood, young adults, and aged healthy donors.
Thu, 20 Apr 2023 - 193 - Review Series on Classical Myeloproliferative NeoplasmsThu, 20 Apr 2023
- 192 - Factor H variants in paroxysmal nocturnal hemoglobinuria, the role of factor XII in SCD-related thrombosis, and clinical features of therapy-related NPM1-mutated AML
In this week’s episode, we’ll learn how rare germline genetic variants in complement factor H (CFH) affect the course of paroxysmal nocturnal hemoglobinuria, discuss the role of coagulation factor XII in thrombotic complications and vaso-occlusion associated with sickle cell disease, and learn more about the overlapping features of therapy-related and de novo NPM1-mutated AML.
Fri, 14 Apr 2023 - 191 - Lenalidomide and genetic profiling in myeloma, T-cell immunotherapy upregulates AML cell MHC-class II, and young fecal microbiota rejuvenate HSCs
In this week’s episode we will review optimizing the value of post-transplant lenalidomide maintenance in multiple myeloma. Next, T-cell immunotherapies targeting AML antigens upregulate MHC Class II expression on AML cells. Finally, young bugs rejuvenate old blood: transplanting fecal microbiota from younger mice into older mice improved hematopoietic stem cell function and restored lymphoid differentiation potential.
Thu, 06 Apr 2023 - 190 - HLA-E-restricted immune response in EBV infection, the role of NRX-0492 in CLL, and NSAIDs for bone marrow failure in Ghosal Hematodiaphyseal Dysplasia
In this week’s episode we’ll learn how HLA-E-restricted immune responses help control Epstein-Barr virus infection, discuss the activity of NRX-0492 in chronic lymphoblastic leukemia, and learn more about the efficacy of non-steroid inflammatory drugs in the treatment of bone marrow failure associated with Ghosal Hematodiaphyseal Dysplasia.
Thu, 30 Mar 2023 - 189 - Review Series on Germ Line Predisposition to Hematologic MalignancyThu, 30 Mar 2023
- 188 - Anti-malaria benefit of hydroxyurea in SCA, IL-22 in the treatment in lower GI acute GVHD, and FLT3-ITD changes depend on context in AML
In this week’s episode we will review a study in sub-Saharan Africa where treatment of sickle cell anemia with hydroxyurea is associated with a lower incidence of malaria. New research suggests mild myelosuppression associated with hydroxyurea treatment may actually have a salutary effect. Next, a potential new treatment approach in lower GI acute GVHD. Adding an interleukin-22 therapy to corticosteroid treatment was well tolerated with a high rate of response in this very challenging patient population. Finally, common AML driver mutations such asFLT3ITD (or internal tandem duplications) orchestrate distinct transcriptional and epigenetic programs based on different genetic contexts. In the context of a common pediatric AML mutation, FLT3ITD selectively activated type I interferon signaling, suggesting a distinct therapeutic vulnerability.
Thu, 23 Mar 2023 - 187 - Single-cell genotyping of MDS/CMML clonal output, VTE risk in diffuse glioma, and Del(1p32) is an adverse prognostic factor in myeloma
In this week’s episode we’ll discuss how azacytidine therapy influences the contributions of mutated HSC clones to hematopoiesis in MDS and CMML, learn more about the risk of venous thromboembolism in patients with adult-type diffuse glioma, and discuss the importance of 1p32 deletions as an independent and adverse prognostic factor in myeloma.
Thu, 16 Mar 2023 - 186 - RUNX1 isoform imbalance drives ML-DS, VWF-binding RNA aptamer for hemophilia A treatment, and EZH1/2 inhibitor valemetostat in relapsed/refractory ATL
In this week’s episode we will review an imbalance among RUNX1 isoforms is key to the pathogenesis of trisomy 21-associated myeloid leukemia, raising the possibility that equilibrium could be restored genetically or pharmacologically. Next, an RNA aptamer demonstrating promising results in patients with hemophilia A. Lastly, phase 2 data on valemetostat, a selective inhibitor of EZH1 and 2, in relapsed or refractory adult T-cell leukemia/lymphoma.
Thu, 09 Mar 2023 - 185 - Phase 3 trial of leniolisib in activated PI3Kδ syndrome, dabrafenib plus trametinib in relapsed/refractory hairy cell leukemia, and TγδLGL leukemia as a more symptomatic subset of leukemia
In this week’s episode, we’ll discuss the findings from a phase 3 trial of PI3Kδ inhibitor leniolisib in activated PI3Kd syndrome, learn more about the efficacy and safety of dabrafenib plus trametinib in relapsed/refractory BRAF V600E mutation-positive hairy cell leukemia, and review the findings from a study conducted in an international cohort of patients with Tγδ LGL leukemia.
Thu, 02 Mar 2023 - 184 - Review Series on Banked Allogeneic Immune Effector CellsThu, 23 Feb 2023
- 183 - Hydroxyurea for secondary stroke prevention in SCD, mutant CALR as a rogue cytokine in MPNs, and parsing pathobiology in Burkitt lymphoma
In this week’s episode we will first review a new clinical trial evidence that for patients with sickle cell anemia in resource limited settings, both low and moderate dose hydroxyurea are effective for secondary stroke prevention. Next, a research article showing how secreted mutant calreticulin functions as a “rogue cytokine” in myeloproliferative neoplasms, acting in a paracrine manner to promote growth of nearby tumor cells. Finally, we’ll review new research on the pathobiology of adult and pediatric Burkitt lymphoma. With the help of whole-genome sequencing, investigators unraveled distinct subgroups, which may provide a new framework for epidemiology, diagnosis, and treatment of these lymphomas.
Thu, 23 Feb 2023 - 182 - HSCT for hypomorphic RAG deficiency, EBV-driven lymphoid neoplasms in pediatric ALL, and clonal hematopoiesis and recurrent vascular events in stroke patients
In this week’s episode we’ll discuss the benefits of early diagnosis and hematopoietic stem cell transplant in patients with hypomorphic RAG deficiency, learn more about EBV-driven lymphoid neoplasms associated with pediatric ALL maintenance therapy, and analyze the associations between clonal hematopoiesis and recurrent vascular events and death in patients with ischemic stroke.
Thu, 16 Feb 2023 - 181 - MRD dynamics during ixazomib maintenance in MM, disparities in CAR T-cell therapy for ALL, and BAX variants and resistance to BH3-mimetics in AML
In this week's episode, we’ll discuss the dynamics of measurable residual disease, or MRD, over time in myeloma patients undergoing ixazomib maintenance. Serial measurements were feasible and provided more detailed risk stratification than single timepoint measurements—findings that could have implications for the use of MRD to guide treatment duration. Up next, a research article exploring the relationships between poverty, and lack of neighborhood opportunity, with outcomes of CAR T -cell therapy in children with acute lymphoblastic leukemia. The findings suggest opportunities for interventions to improve access for less socioeconomically advantaged children. Finally, we’ll review a report demonstrating that acquired mutations in the pro-apoptotic effector protein BAX are common in patients with AML treated with venetoclax. These and other research observations reveal BAX variants as a hurdle to the long-term success of BCL2-targeted therapy in this disease.
Thu, 09 Feb 2023 - 180 - Itacitinib monotherapy for GVHD, the role of ERG in EVI1-driven AML, and germline DDX41 mutations in myeloid neoplasms
In this week's episode, we’ll discuss the safety and efficacy of itacitinib monotherapy in low-risk acute GVHD, learn how ERG was discovered to be a key transcriptional target in EVI1-driven AML, and define a unique subtype of myeloid neoplasms characterized by germline DDX41 mutations.
Thu, 02 Feb 2023 - 179 - Blood Review Series on Single-Cell Genomics
In this bonus episode Associate Editor, Dr. Bertie Göttgens and Dr. Ravi Majeti discuss the series on Single Cell Genomics and Heme Malignancies-Leukemia/MPNs.
Thu, 26 Jan 2023 - 178 - Stem cell transplant for SCD normalizes brain blood flow, novel GALE variants disrupt platelet development, and revisiting risk classification in NPM1-mutant AML
In this week’s episode, new research shows that in children with sickle cell disease, stem cell transplantation normalizes blood flow in the brain. The improvements in cerebral hemodynamics seen in this study may help explain the stroke protection seen following transplant in this high-risk patient population. Next up, a research article providing new insights on thrombocytopenia related to the GALE gene, including the identification of several previously unreported variants. The findings highlight the importance of GALE in the glycosylation of proteins that play a role in the production and function of platelets. Finally, we’ll review a brief report on NPM1-mutated AML with adverse cytogenetics in light of the updated ELN 2022 classification. In short, adverse-risk cytogenetics remain significantly associated with unfavorable prognosis under the refined definitions, supporting the recent categorization of this entity as adverse-risk.
Thu, 26 Jan 2023 - 177 - Allogeneic transplantation in older and infirm AML patients, cilta-cel in progressive multiple myeloma, and anti-CD20 therapy in relapsed TTP
In this week’s episode we’ll discuss the benefits of allogeneic hematopoietic stem cell transplantation in older and medically infirm patients with AML, learn more about the efficacy and safety of cilta-cel in patients with progressive multiple myeloma after exposure to other BCMA-targeting agents, and review the role of anti-CD20 therapy in relapsed immune-mediated thrombotic thrombocytopenic purpura.
Thu, 19 Jan 2023 - 176 - Piezo antigens define a new blood group system, enasidenib in mutant-IDH2 relapsed/refractory AML, and breakthrough COVID-19 despite prophylaxis in B-cell malignancies
In this week’s episode, we’ll discuss new research revealing that the mechanosensory ion channel Piezo1 is the elusive carrier molecule of the Er blood group antigens, thus establishing a new blood group system. Next, we review results of a randomized phase 3 trial of enasidenib versus conventional treatment in late-stage mutant-IDH2 relapsed or refractory AML. Although the primary endpoint of overall survival was not met, investigators say the risk benefit ratio remains positive. Finally, we’ll review a study showing a clinically significant risk of breakthrough COVID-19 infections in patients with B-cell malignancies despite vaccination and pre-exposure prophylaxis with tixagevimab-cilgavimab during the Omicron era. However, hospitalization rates in the study were low and no deaths were reported.
Thu, 12 Jan 2023 - 175 - How I Treat Series: Management of High-risk Patients Following Allogeneic Transplant
In this episode, Associate Editor, Dr. Robert Zeiser and Dr. Yi-Bin Chen discuss the series on How I Manage High-Risk Patients Following Allogeneic Hematopoietic Cell Transplantation.
Thu, 05 Jan 2023 - 174 - Immune thrombocytopenia in pregnancy, ASCT in adults with inborn errors of immunity, and long-term health outcomes of childhood AML survivors
In this week’s episode we’ll discuss whether pregnancy increases the risk of bleeding in women with immune thrombocytopenia, compare the outcomes of allogeneic stem cell transplantation versus conservative management in adults with inborn errors of immunity, and learn more about the long-term health outcomes and late mortality in childhood AML survivors.
Thu, 05 Jan 2023 - 173 - IL-13/IL-4 signaling and fibrotic progression in myelofibrosis, VWF-targeted thrombolysis in acute ischemic stroke, and NK cell dysfunction in relapsed AML
In this week’s episode, we'll discuss involvement of IL-13 and IL-4 signaling in fibrotic progression of myelofibrosis; next, we review results on a novel agent using vWF-dependent mechanisms to lyse pathological thrombi in acute ischemic stroke. Finally, we’ll shed new light on findings that implicate the GARP-TGF-beta-1 pathway in the loss of natural killer cell cytotoxicity in relapsed AML.
Thu, 29 Dec 2022 - 172 - Effects of iron repletion on donor RBC quality, long-term outcomes in relapsed/refractory hairy cell leukemia after vemurafenib, and off-the-shelf cryopreserved platelets for detecting HIT
In this week’s episode, we’ll discuss the effects of iron repletion on the quality of donated red blood cells and donor well-being, learn more about the long-term outcomes of patients with relapsed/refractory hairy cell leukemia after vemurafenib monotherapy, and discuss the use of off-the-shelf cryopreserved platelets for detecting heparin-induced thrombocytopenia and vaccine-induced immune thrombotic thrombocytopenia.
Thu, 22 Dec 2022 - 171 - Germline predisposition variants occur in all age groups in MDS, αβ-haplo-HCT excels in children with acute leukemias/MDS, and poor outcomes after CAR T cell failure in B-cell lymphomas
In this week’s episode, research shows that in patients with myelodysplastic syndromes, or MDS, the frequency of pathogenic or likely pathogenic germline variants is relatively high across all age groups, not just younger patients. Based on these results, it may be time to expand genetic testing to all patients. Next, we'll review primary results of a prospective, multicenter study of children with acute leukemias or MDS who underwent T-cell receptor αβ+ and CD19+ cell-depleted haploidentical HCT with reduced-toxicity conditioning. Finally, an emerging unmet need related to CAR T cell therapy: patients who progress after receiving CAR T cells have poor outcomes and no agreed upon standard of care. We’ll review findings from a large registry study demonstrating infrequent responses to post-CAR T cell treatment and short survival times, highlighting a need for novel strategies.
Thu, 15 Dec 2022 - 170 - Predicting VTE in multiple myeloma, azithromycin promotes relapse after HSCT, and dual antigen targeted NK cells in B cell malignancies
In this week’s episode we’ll discuss the newly developed PRISM score for risk prediction of venous thromboembolism in multiple myeloma, learn more about relapse-promoting effects of azithromycin after allogeneic stem cell transplantation, and discuss the efficacy of off-the-shelf natural killer cells in preventing antigen escape in lymphoma and leukemia.
Thu, 08 Dec 2022 - 169 - Using MRD to guide CLL treatment intensity, donor NK cells boost immune reconstitution after haplo-BMT, and EZH2 drives retinoic acid resistance in variant APL
In this week’s episode we discuss encouraging results of a phase 2 study using a sequential ibrutinib-venetoclax treatment approach driven by MRD findings in individual patients with chronic lymphocytic leukemia, or CLL. Next, we examine new research demonstrating that donor natural killer cells trigger release of beta-2 microglobulin by host dendritic cells, greatly accelerating donor-derived immune reconstitution after allogeneic bone marrow transplant in mice. We’ll look at the therapeutic implications of this as well. Lastly, we review a study of retinoic acid resistance in a mouse model of variant acute promyelocytic leukemia. Resistance was driven by the epigenetic regulator EZH2, which suggests the potential for an EZH2-targeted therapeutic approach.
Thu, 01 Dec 2022 - 168 - Tolerability of CD19 CAR T cells in lymphoma, causes of platelet spherocytosis, and using prebiotics to reduce GVHD
In this week’s episode, we’ll discuss patient-reported outcomes in the phase 3 ZUMA-7 trial of CAR T-cell therapy in second-line relapsed/refractory large B-cell lymphoma, learn more about the association between the loss of α4A- and β1-tubulin and severe platelet spherocytosis, and discuss the interaction between prebiotic galactooligosaccharides and mouse gut microbiota in graft-versus-host disease.
Thu, 24 Nov 2022 - 167 - Transplant in adult Ph+ ALL, acalabrutinib and ventricular arrythmias, and antibody prevention of fetal/neonatal alloimmune thrombocytopenia
In this week’s episode we discuss the role of allogeneic transplant in adult patients with Philadelphia chromosome-positive acute lymphoblastic leukemia. In a retrospective study, transplant provided no survival benefit in patients with rapid and deep responses to induction therapy that included BCR-ABL1 inhibitors. Up next, we discuss the evidence for an increased risk of ventricular arrythmias with use of acalabrutinib, which has emerged as a class effect of Bruton tyrosine kinase inhibitors. Lastly, we examine a novel, alloantigen-specific model to test the efficacy of a prophylactic treatment strategy for preventing fetal/neonatal alloimmune thrombocytopenia.
Thu, 17 Nov 2022 - 166 - Restricting dietary methionine in AML, transferrin in high altitude-induced hypercoagulability, and LIF as protection against GVHD
In this week’s episode, we’ll learn more about the impact of dietary methionine restriction on the progression of AML, discuss transferrin upregulation as a cause of high-altitude-induced hypercoagulability, and learn more about the protective effects of leukemia inhibitory factor against graft-versus-host disease.
Thu, 10 Nov 2022 - 165 - Sickle hemoglobin activates monocytes via TLR4, germinal center B cells provide a niche for T-cell lymphoma, and a combination immunosuppression regimen for acquired hemophilia A
In this week’s episode, we will review a study that cell-free hemoglobin S was found to induce high levels of pro-inflammatory cytokine production in monocytes. The effect is mediated by Toll-like receptor 4, or TLR4, suggesting intriguing therapeutic possibilities for sickle cell disease. Secondly, germinal center B cells with aberrant expression profiles undergo independent clonal evolution in the microenvironment of angioimmunoblastic T-cell lymphoma. New findings published in Blood elucidate mechanisms of disease pathogenesis and uncover a new potential target for treatment. Finally, an upfront combination of three immunosuppressive agents was highly effective and well tolerated in patients with acquired hemophilia A. Although prospective studies are needed, the triple regimen could be an attractive treatment option, particularly for elderly and frail patients.
Thu, 03 Nov 2022 - 164 - Lineage switching in MLL/AF4 leukemia, ibrutinib in mantle cell lymphoma with CNS relapse, and gilteritinib plus azacitidine in newly diagnosed FLT3-mutated AML
In this week’s episode we’ll discuss the role of epigenetic regulator genes in lineage switching in MLL/AF4 leukemia, learn more about the efficacy of ibrutinib in mantle cell lymphoma with central nervous system relapse, and discuss the findings from a phase 3 trial of gilteritinib plus azacitidine in patients with newly diagnosed FLT3-mutated AML.
Thu, 27 Oct 2022 - 163 - Blood Review Series on Megakaryopoiesis and Platelet Production
Megakaryocytes contribute to multiple processes in the body, including platelet production and regulation of hematopoietic stem cells. Therefore, it is not surprising that alterations in this lineage not only affect platelets but also impact hematopoiesis in other ways. Fortunately, our understanding of megakaryocyte biology has increased significantly with the advent of advanced technologies such as next-generation sequencing and sophisticated microscopy.
Thu, 20 Oct 2022 - 162 - Lenalidomide and subsequent TP53-mutated myeloid neoplasms, abnormal uterine bleeding after VTE, and novel tri-specific antibody for B-ALL
In this week’s episode we will review data showing that lenalidomide promotes development of TP53-mutated, therapy-related myeloid neoplasms. Next, we'll discuss the first prospective study to evaluate abnormal uterine bleeding in women starting anticoagulation for venous thromboembolism. Lastly, we'll review an optimized tri-specific antibody that overcomes immune escape and enhances therapeutic efficacy in a patient-derived xenograft model of B-cell ALL.
Thu, 20 Oct 2022 - 161 - Prognostic impact of NPM1 and FLT3 mutations in AML, progression of monoclonal B cell lymphocytosis, and creating RBCs with rare blood types in the laboratory
In this week’s episode we’ll learn more about the prognostic impact of NPM1 and FLT3 mutations in AML, discuss the progression and survival of monoclonal B-cell lymphocytosis, and learn more about the use of red blood cells derived from pluripotent stem cells in transfusion medicine.
Thu, 13 Oct 2022 - 160 - Transplant outcomes in adults with immunodeficiencies and erythroblastic islands as niches for terminal erythropoiesis and granulopoiesis
In this week’s episode we'll review results of the largest retrospective study to date of allogeneic transplantation in adult patients with inborn errors of immunity. We’ll then discuss intriguing new research demonstrating that erythroblastic islands in the bone marrow foster granulopoiesis alongside terminal erythropoiesis—which lays a foundation for better understanding how blood cell production is regulated within these niches.
Fri, 07 Oct 2022 - 159 - Ticagrelor in pediatric sickle cell disease, UBA1 translation impacts severity of VEXAS syndrome, and T-cell immunity and chemotherapy response in ALL
In this week’s episode we’ll learn more about the negative findings from the phase three trial of ticagrelor for preventing vaso-occlusive crises in children with sickle cell disease, discuss how residual cytoplasmic UBA1 contributes to the pathogenesis of VEXAS syndrome, and learn more about the impact of host T-cell immunity in the response to chemotherapy in pediatric ALL.
Thu, 29 Sep 2022 - 158 - Race affects treatment outcomes in iTTP, 2022 ELN AML recommendations, and a comprehensive MRD assessment in MCL
In this week’s episode we’ll take a quick look at the latest European Leukemia Net recommendations for the diagnosis and management of acute myeloid leukemia. We’ll also describe a comprehensive analysis of a phase 3 trial indicating that MRD is a strong outcome predictor over the entire natural history of mantle cell lymphoma, setting the stage for potential risk stratification tools that may be suitable for MRD-guided treatment. We'll also look at a large US registry study demonstrating that black patients with idiopathic thrombotic thrombocytopenic purpura had a shorter time to relapse and less response to rituximab compared to white patients. These findings suggest a potential need for closer monitoring, early retreatment, and alternative treatments.
Thu, 22 Sep 2022 - 157 - The International Consensus Classification: An interview with Drs. Daniel Arber and Elias Campo
In this bonus episode, we’re delighted to have Dr. Dan Arber from the University of Chicago and Dr. Elias Campo from the University of Barcelona. With members of the Clinical Advisory Committee, Drs. Arber and Campo led efforts to develop the new International Consensus Classification for what we refer to as the ICC.
Thu, 15 Sep 2022
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