Hematology

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About 25% of essential thrombocythemia (ET) patients present with extreme thrombocytosis (ExT), defined as having a platelet count ≥1000 x 10^9/L. ExT patients may have an increased bleeding risk associated with acquired von Willebrand syndrome. We retrospectively analyzed the risk of bleeding and thrombosis in ExT vs. non-ExT ET patients at Dana Farber Cancer Institute and Massachusetts General Hospital from 2014-2022 to inform treatment decisions. We abstracted the first major bleed, clinically relevant non-major bleed (CRNMB), and thrombotic event from medical records...

Non-adherence to direct oral anticoagulants (DOACs) pharmacotherapy may increase the risks of thromboembolism or bleeding, and delayed or missed doses are the most common types of non-adherence. Current recommendations from regulatory agencies or guidelines regarding this issue lack evidence and fail to consider individual differences. The study aims to develop individual remedial dosing strategies when the dose was delayed or missed for DOACs including rivaroxaban, apixaban, edoxaban, and dabigatran etexilate...

Current guidelines for treating vaccine-induced immune thrombotic thrombocytopenia (VITT) recommend non-heparin anticoagulants and intravenous immunoglobulin (IVIg). However, the efficacy of these treatments remains uncertain due to case studies involving small patient numbers, confounding factors (e.g. concurrent treatments), and a lack of animal studies. A recent study proposed danaparoid and heparin as potential VITT therapies due to their ability to disrupt VITT IgG-PF4 binding. Here, we examined the effects of various anticoagulants (including unfractionated (UF) heparin, danaparoid, bivalirudin, fondaparinux, and argatroban), IVIg, and the FcγRIIa receptor-blocking antibody, IV...

No abstract text is available yet for this article.

According to the diagnostic criteria for HHV-8 (human herpesvirus-8) negative/idiopathic multicentric Castleman disease (iMCD) proposed by Castleman Disease Collaborative Network (CDCN) in 2017, there is a group of HHV-8 negative multicentric Castleman disease (MCD) patients who do not have symptoms and hyperinflammatory state and do not meet the iMCD criteria. This retrospective study enrolled 114 such patients, described as asymptomatic MCD (aMCD), from 26 Chinese centers from 2000-2021. With a median follow-up time of 46...

Patients with relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL) ineligible for available salvage therapies have limited options for long-term disease control, necessitating novel treatments. Previously, magrolimab (anti-cluster-of-differentiation-47 antibody) plus rituximab (M+R) demonstrated ability to induce complete responses (CR) in R/R DLBCL. Here we report 3-year follow-up data from this phase 1b/2 study (NCT02953509) assessing long-term safety and efficacy of M+R, and initial safety and efficacy of M+R plus gemcitabine-oxaliplatin (M+R-GemOx), in R/R DLBCL...

Hematopoietic stem cell transplantation with lentiviral vector (LVV) transduced autologous cells has proven an effective therapeutic strategy for sickle cell disease (SCD). However, ex vivo culture or proliferative stress associated with in vivo reconstitution may amplify any underlying genetic risk of leukemia. We aimed to minimize culture-induced stress and reduce genomic damage during ex vivo culture, enhance stem cell fitness and reconstitution of SCD CD34+ cells transduced with BCL11A shmiR-encoding LVV currently in clinical trials (NCT NCT03282656)...

The BCL2-inhibitor Venetoclax (VEN) in combination with hypomethylating agents (HMA) has been approved for first-line treatment of acute myeloid leukemai (AML) patients ineligible for intensive treatment. Emerging Data suggest that VEN containing treatment strategies may also be effective in relapsed/refractory (R/R) AML, however, comparative studies with conventional treatment strategies for medically fit patients as a bridge-to transplant strategy are limited. Using propensity score matching (PSM) analysis, we compared 37 R/R AML patients, who received VEN-based salvage therapy as bridge to allogeneic hematopoietic cell transplantation (allo-HCT) with 90 patients from the German Study Alliance Leukemia (SAL) AML registry, who were treated with non-VEN-containing salvage therapy according to their treating physician's choice (TPC) including intensive and non-intensive protocols...

Few data exist regarding the tumor B-cell receptor (BCR) repertoire and lymphoid microenvironment in primary mediastinal B-cell lymphoma (PMBL). We applied 5' rapid amplification of cDNA ends (5'RACE) to tumor RNA samples from 137 PMBL patients with available gene expression profiling and next-generation sequencing data. We obtained 5'RACE results for 75/137 (54.7%) patients, with clinical characteristics as follows: median [min-max] age, 33 [18-64] years; female, 53.3%; ECOG score 0-1, 86.7%; stage I-II, 57...

Allogeneic hematopoietic stem cell transplantation is an established treatment for hematological malignancies and some genetic diseases. Acute graft versus host disease (GVHD) is the most common and debilitating side effect with poor survival rates of 5-30% for severe cases. In this manuscript, we describe a tetravalent T cell-engaging bispecific antibody (BsAb) based on the IgG-[L]-scFv platform, with all four binding domains specific for CD3. In vitro, picomolar concentrations of the CD3×CD3 BsAb induced potent lysis of activated CD4 and CD8 T cells...

The pathogenesis of MYC and BCL2 double expressor diffuse large B-cell lymphoma (DE-DLBCL) remains unclear. To investigate how MYC and BCL2 contribute to tumor aggressiveness, we analyzed tumors from 14 patients each with DE- and non-DE-DLBCL patients by whole transcriptome sequencing. Validation was performed using publicly available datasets, tumor tissues from 126 patients, DLBCL cell lines, and a syngeneic mouse lymphoma model. Our transcriptome analysis revealed significantly elevated mRNA levels of C-C motif chemokine ligand 2 (CCL2) and C-C chemokine receptor type 2 (CCR2) in DE-DLBCLs compared to non-DE-DLBCLs (Padj < 0...

Prior to the advent of effective iron chelation, death from iron-induced cardiomyopathy and endocrine failure occurred in the second decade in patients with thalassemia major and this experience has driven expectation of poor outcomes and caused anxiety in all disorders associated with iron loading to this day. To be clear, severe iron overload still causes significant morbidity and mortality in many parts of the world, but current understanding of iron metabolism, non-invasive monitoring of organ specific iron loading in humans and effective iron chelators have dramatically reduced morbidity of iron overload...

Quantitative immuneprecipitation mass-spectrometry (QIP-MS) allows the identification of the M-protein in patients with multiple myeloma (MM) otherwise in complete response, and could be considered suitable for measurable residual disease (MRD) evaluation in peripheral blood. In the context of the GEM2012MENOS65 and GEM2014MAIN trials, we compared the performance of QIP-MS in serum with next-generation flow (NGF) cytometry in bone marrow to assess MRD in paired samples obtained post-induction, transplant, consolidation and after 24 cycles of maintenance...

A "restrictive" red blood cell transfusion threshold, hemoglobin concentration <7-8 g/dL, has long been recommended for most hospitalized patients including anemic patients with stable cardiovascular disease (CVD). Although no threshold recommendation is given for acute coronary syndromes (ACS), recent evidence suggests that "liberal" rather than "restrictive" transfusion strategies are associated with significantly improved safety for hospitalized patients with stable CVD and/or ACS. This finding suggests that previously available data were misinterpreted...

IMPORTANCE: Utilization of hematopoietic cell transplantation (HCT) for hematologic cancers previously demonstrated race, ethnicity, and age-based disparities. OBJECTIVE: To evaluate utilization over time by race, ethnicity, and age to determine if disparities persist in light of recent significant increases in HCT volume. DESIGN, SETTING, AND PARTICIPANTS: This US population-based retrospective cohort study includes patients who received transplants from January 2009 to December 2018...

Approximately 7% of patients with newly diagnosed multiple myeloma (MM) experience bleeding complications with varying causes, but few reports have described these complications. Here we report the case of a patient with newly diagnosed MM who presented with a bleeding tendency and various coagulation abnormalities. Chromogenic assays, thrombin time, and reptilase time revealed the presence of a thrombin-inhibiting substance that inhibited release of fibrinopeptide A from fibrinogen. The coagulation abnormalities improved after treatment with daratumumab, lenalidomide, and dexamethasone...

OBJECTIVE: Pro-resolving molecules, including the peptide Angiotensin-(1-7) [Ang-(1-7)], have potential adjunctive therapy for infections. Here we evaluate the actions of Ang-(1-7) in betacoronavirus infection in mice. METHODS: C57BL/6J mice were infected intranasally with the murine betacoronavirus MHV-3 and K18-hACE2 mice were infected with SARS-CoV-2. Mice were treated with Ang-(1-7) (30 µg/mouse, i.p.) at 24-, 36-, and 48-hours post-infection (hpi) or at 24, 36, 48, 72, and 96 h...

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BACKGROUND: Chagas disease (CD) is a serious public health problem in Latin America. Benznidazole (BNZ) is used for the treatment of CD and, despite its wide use, little information is available about its toxicity and mechanisms of adverse drug reactions (ADR). OBJECTIVES: To identify and classify clinical and laboratory adverse reactions caused by BNZ in terms of causality and severity. METHODS: Prospective cohort study from January 2018 to December 2021...