Hereditary angioedema (HAE), caused by C1 inhibitor protein deficiency, was recently shown to be associated with an increased risk for venous thromboembolism (VTE). To our knowledge, this is the first national family study of HAE, which aimed to determine the familial risk of VTE. The Swedish Multi-Generation Register was linked to the Swedish National Patient Register for the period of 1964 to 2018

Molecular measurable residual disease can persist in core-binding factor acute myeloid leukemia in otherwise disease-free patients. Utilizing cell sorting followed by fluorescent in situ hybridization, we show that detection is due to mast cells.

Hemolytic disease of the fetus and newborn (HDFN) remains an important cause of perinatal morbidity and mortality. HDFN is caused by maternal alloimmunization with red blood cell (RBC) antigens. This article describes and highlights the issues in the care of pregnant women with RBC alloimmunization. This includes monitoring for, and management of fetal anemia caused by maternal red cell alloantibodies

T- and natural killer (NK)-cell lymphomas are neoplasms derived from immature T cells (lymphoblastic lymphomas), or more commonly, from mature T and NK cells (peripheral T-cell lymphomas, PTCLs). PTCLs are rare but show marked biological and clinical diversity. They are usually aggressive and may present in lymph nodes, blood, bone marrow, or other organs. More than 30 T/NK-cell–derived neoplastic

Adult hematopoietic stem and progenitor cells (HSPCs) reside in the bone marrow (BM) hematopoietic niche, which regulates HSPC quiescence, self-renewal, and commitment in a demand-adapted manner. Although the complex BM niche is responsible for adult hematopoiesis, evidence exists for simpler, albeit functional and more accessible, extramedullary hematopoietic niches. Inspired by the anecdotal description

Acquisition of a hyperdiploid (HY) karyotype or immunoglobulin heavy chain (IgH) translocations are considered key initiating events in multiple myeloma (MM). To explore if other genomic events can precede these events, we analyzed whole-genome sequencing data from 1173 MM samples. By integrating molecular time and structural variants within early chromosomal duplications, we indeed identified pregain

It is unclear whether risk of infection is increased in individuals with hereditary hemochromatosis and in individuals with low or high plasma iron, transferrin saturation, or ferritin. Therefore, we tested whether high and low iron, transferrin saturation, and ferritin are associated with risk of infections observationally and genetically through genotypes. We studied 142 188 Danish general population

In patients with myelodysplastic syndrome (MDS) higher revised International Prognostic Scoring System (IPSS-R) scores at transplant are associated with worse transplant outcome. Thus, it may seem beneficial to improve IPSS-R scores by therapeutic intervention before transplantation in order to “downstage” the disease risk. However, there is no evidence, to date, to support this approach. A retrospective

B-cell maturation antigen (BCMA)–targeting therapeutics have dramatically improved outcomes in relapsed/refractory multiple myeloma (RRMM). However, whether the mechanisms of resistance between these therapies are shared and how the identification of such mechanisms before therapy initiation could refine clinical decision-making remains undefined. We analyzed outcomes for 72 RRMM patients treated with

Transfusion of red blood cells (RBCs) can be lifesaving for individuals living with sickle cell disease (SCD). However, alloimmunization after transfusion is more common with patients with SCD than in other patient populations, resulting in morbidity and mortality. Management of complications related to RBC alloantibodies, including delayed hemolytic transfusion reactions (DHTRs) and identifying compatible

Over the last decades, significant improvements in reducing the toxicities of allogeneic hematopoietic cell transplantation (allo-HCT) have widened its use as consolidation or salvage therapy for high-risk hematological malignancies. Nevertheless, relapse of the original malignant disease remains an open issue with unsatisfactory salvage options and limited rationales to select among them. In the last

For many years, it has been known that von Willebrand factor (VWF) interacts with factor VIII, collagen, and platelets. In addition, the key roles played by VWF in regulating normal hemostasis have been well defined. However, accumulating recent evidence has shown that VWF can interact with a diverse array of other novel ligands. To date, >60 different binding partners have been described, with interactions

It has been known for over half a century that humans produce different forms of hemoglobin, a tetramer of α- and β-like hemoglobin chains, throughout ontogeny. The switch from fetal-to-adult hemoglobin occurs around the time of birth when erythropoiesis shifts from the fetal liver to the bone marrow. Naturally, diseases caused by defective adult β-globin genes, such as sickle cell disease and β-thalassemia

The success of hematopoietic transplantation for hemoglobinopathies and hematological malignancies has been accompanied by the new challenge of how to identify, risk stratify, and treat iron overload and toxicity before and after transplantation. Substantial progress has been made in our understanding of iron metabolism and the pathophysiology of iron overload, making us aware that not only the total

Venous thrombosis (VT) is a serious medical condition in which a blood clot forms in deep veins, often causing limb swelling and pain. Current antithrombotic therapies carry significant bleeding risks resulting from targeting essential coagulation factors. Recent advances in this field have revealed that the cross talk between the innate immune system and coagulation cascade is a key driver of VT pathogenesis

Complete remission with partial hematological recovery (CRh) has been used as an efficacy end point in clinical trials of nonmyelosuppressive drugs for acute myeloid leukemia (AML). We conducted a pooled analysis to characterize the clinical outcomes for patients with AML who achieved CRh after treatment with ivosidenib, olutasidenib, enasidenib, or gilteritinib monotherapy in clinical trials used

Measurable residual disease (MRD) evaluation by multiparameter flow cytometry (MFC) or quantitative polymerase chain reaction methods is an established standard of care for assessing risk of relapse before or after hematopoietic cell transplantation (HCT) for acute lymphoblastic leukemia (ALL). Next-generation sequencing (NGS)–MRD has emerged as a highly effective approach that allows for the detection

The leucine-rich repeat-containing G-protein–coupled receptor 6 (LGR6) was recently identified as the cognate receptor for the proresolving mediator maresin 1 (MaR1). To address the biological role of LGR6 in humans, we investigated the functional impact of a genetic variant in the gene encoding for , which is predicted to lead to a frameshift mutation in one of the receptor isoforms, on both receptor

We hypothesized that fit older patients with acute myeloid leukemia (AML) treated with decitabine (DEC) would report better health-related quality of life (HRQoL) outcomes than those receiving intensive chemotherapy (IC). We conducted a phase 3 randomized trial to compare DEC (10-day schedule) with IC (3+7) in older fit patients with AML. HRQoL was a secondary end point, and it was assessed with the

Mass spectrometry (MS) can detect multiple myeloma–derived monoclonal proteins in the peripheral blood (PB) with high sensitivity, potentially serving as a PB assay for measurable residual disease (MRD). This study evaluated the significance of PB MS MRD negativity during posttransplant therapy in patients with newly diagnosed multiple myeloma. Serum samples from 138 patients treated in the phase 3

Glucocorticoids are key components of the current standard-of-care regimens (eg, R-CHOP [rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone], EPOCH-R [etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab], and hyper-CVAD [cyclophosphamide, vincristine, doxorubicin, dexamethasone, methotrexate, and cytarabine]) for the treatment of B-cell malignancy. However

Rearrangements that place the oncogenes , , or adjacent to superenhancers are common in mature B-cell lymphomas. Lymphomas with diffuse large B-cell lymphoma (DLBCL) or high-grade morphology with both and rearrangements are classified as high-grade B-cell lymphoma with and rearrangements (“double hit”; HGBCL-DH-) and are associated with aggressive disease and poor outcomes. Although it is established

This meta-analysis evaluates the efficacy and safety of chimeric antigen receptor (CAR) T-cell therapy and bispecific antibodies for relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL). We searched MEDLINE, Embase, and Cochrane databases until July 2023 for trials assessing CAR T-cell therapies and CD20×CD3 bispecific antibodies as third or subsequent lines in R/R DLBCL. Random-effects models

Relapse is the leading cause of death after allogeneic hematopoietic stem cell transplantation (HCT) for leukemia. Expression of T-cell receptors (TCR), using T cells engineered by gene transfer (TCR-T), specific for hematopoiesis–restricted minor histocompatibility (H) antigens, may provide a potent selective antileukemic effect after HCT. We conducted a phase 1 clinical trial using a novel TCR-T

Serial cardiovascular magnetic resonance evaluation of children and young adults with sickle cell disease who underwent hematopoietic cell transplantation showed mean ECV, representing diffuse myocardial fibrosis, decreased 3.4% from baseline to 12-months post-HCT. This trial was registered at as #NCT04362293.

Although -mutated acute myeloid leukemia (AML) carries a generally favorable prognosis, many patients still relapse and die. Previous studies identified several molecular and clinical features associated with poor outcomes; however, only -internal tandem duplication (ITD) mutation and adverse karyotype are currently used for risk stratification because of inconsistent results and uncertainty about

Hematopoietic stem cells (HSCs) are characterized by the ability to self-renew and to replenish the hematopoietic system. The cell-cycle kinase cyclin-dependent kinase 6 (CDK6) regulates transcription, whereby it has both kinase-dependent and kinase-independent functions. Herein, we describe the complex role of CDK6, balancing quiescence, proliferation, self-renewal, and differentiation in activated

The T-box transcription factor T-bet is known as a master regulator of the T-cell response but its role in malignant B cells has not been sufficiently explored. Here, we conducted single-cell resolved multi-omics analyses of malignant B cells from patients with chronic lymphocytic leukemia (CLL) and studied a CLL mouse model with a genetic knockout of . We found that T-bet acts as a tumor suppressor

HLA-mismatched transplants with either in vitro depletion of CD3 T-cell receptor (TCR)αβ/CD19 (TCRαβ) cells or in vivo T-cell depletion using posttransplant cyclophosphamide (PTCY) have been increasingly used for patients with inborn errors of immunity (IEIs). We performed a retrospective multicenter study via the EBMT registry on 306 children with IEIs undergoing their first transplant between 2010

Histologic transformation of Waldenström macroglobulinemia (HT-WM) carries a poor prognosis with standard treatments. Here, we report the first series of HT-WM treated with chimeric antigen receptor T cells showing a high efficacy and no unexpected toxicity.

Obinutuzumab (O) and rituximab (R) are 2 CD antibodies that have never been compared in a prospective randomized trial of mantle cell lymphoma (MCL). Herein, we report the long-term outcome of the LyMa-101 trial , in which newly diagnosed patients with MCL were treated with chemotherapy plus O before transplantation, followed by O maintenance (O group). We then compared these patients with those treated

In the phase 2 clinical trial (AIM) of venetoclax-ibrutinib, 24 patients with mantle cell lymphoma (MCL; 23 with relapsed/refractory [R/R] disease) received ibrutinib 560 mg and venetoclax 400 mg both once daily. High complete remission (CR) and measurable residual disease negative (MRD-negative) CR rates were previously reported. With median survivor follow-up now exceeding 7 years, we report long-term

Patients with acute myeloid leukemia (AML) who experience relapse following allogeneic hematopoietic cell transplantation (alloHCT) face unfavorable outcomes regardless of the chosen relapse treatment. Early detection of relapse at the molecular level by measurable residual disease (MRD) assessment enables timely intervention, which may prevent hematological recurrence of the disease. It remains unclear

Thrombotic microangiopathy (TMA) is characterized by immunothrombosis and life-threatening organ failure but the precise underlying mechanism driving its pathogenesis remains elusive. In this study, we hypothesized that gasdermin D (GSDMD), a pore-forming protein that serves as the final downstream effector of the pyroptosis/interleukin-1 beta (IL-1β) pathway, contributes to TMA and its consequences

Teclistamab, an off-the-shelf B-cell maturation antigen (BCMA) × CD3 bispecific antibody that mediates T-cell activation and subsequent lysis of BCMA-expressing myeloma cells, is approved for the treatment of patients with relapsed/refractory multiple myeloma (R/RMM). As a T-cell redirection therapy, clinical outcomes with teclistamab may be influenced by patient immune fitness and tumor antigen expression

Hematopoietic differentiation is controlled by intrinsic regulators and the extrinsic hematopoietic niche. Activating transcription factor 4 (ATF4) plays a crucial role in the function of fetal and adult hematopoietic stem cell maintenance. However, the precise function of ATF4 in the bone marrow (BM) niche and the mechanism by which ATF4 regulates adult hematopoiesis remain largely unknown. Here,

Philadelphia chromosome–like acute lymphoblastic leukemia (Ph-like ALL) represents a high-risk B-lineage ALL subtype characterized by adverse clinical features and poor relapse-free survival despite risk–adapted multiagent chemotherapy regimens. The advent of next-generation sequencing has unraveled the diversity of kinase-activating genetic drivers in Ph-like ALL that are potentially amenable to personalized

Rare subtypes of peripheral T-cell lymphoma (PTCL) including enteropathy–associated T-cell lymphoma (EATL), monomorphic epitheliotropic intestinal T-cell lymphoma (MEITL), subcutaneous panniculitis–like T-cell lymphoma (SPTCL), and hepatosplenic T-cell lymphoma (HSTCL) are underrepresented in most registries and clinical studies. Most of the literature is obtained from small case series, single-institution

In this retrospective study, chimeric antigen receptor T cells remained effective in patients with relapsed/refractory large B-cell lymphoma after prior exposure to bispecific antibodies (BsAbs) targeting different antigens. These results are relevant to clinical practice, particularly given the increasing use of BsAbs in earlier treatment lines.

Triple-negative breast cancer (TNBC) is an aggressive tumor entity in which immune checkpoint (IC) molecules are primarily synthesized in the tumor environment. Here, we report that procoagulant platelets bear large amounts of such immunomodulatory factors and that the presence of these cellular blood components in TNBC relates to protumorigenic immune-cell activity and impaired survival. Mechanistically

A reciprocal t(3;8) :: fusion is common in large B-cell lymphoma (LBCL) with and disruption. These pseudo–double-hit cases are not adverse, whereas t(3;8)/ lymphoma has an inferior prognosis relative to other -rearranged LBCL.

Posttransplant lymphoproliferative disorder (PTLD) is a rare complication of solid organ transplantation, and cytotoxic chemotherapy is associated with treatment-related morbidity and mortality. Current treatment takes a sequential, risk-stratified approach, and patients with low-risk disease after initial immunotherapy can avoid escalation to immunochemotherapy. TIDaL is a prospective, single-arm

We investigated efficacy and safety of mavorixafor, an oral CXCR4 antagonist, for participants with warts, hypogammaglobulinemia, infections, and myelokathexis (WHIM) syndrome, a rare immunodeficiency caused by gain-of-function variants. This randomized (1:1), double-blind, placebo-controlled, phase 3 trial enrolled participants aged ≥12 years with WHIM syndrome and absolute neutrophil count (ANC)

Selecting the most suitable alternative donor becomes challenging in severe aplastic anemia (SAA) when a matched sibling donor (MSD) is unavailable. We compared outcomes in patients with SAA undergoing stem cell transplantation (SCT) from matched unrelated donors (MUD) (n = 1106), mismatched unrelated donors (MMUD) (n = 340), and haploidentical donors (Haplo) (n = 206) registered in the European Society

Plasma cells (PCs) are highly specialized cells representing the end stage of B-cell differentiation. We have shown that PC differentiation can be reproduced in vitro using elaborate culture systems. The molecular changes occurring during PC differentiation are recapitulated in this in vitro differentiation model. However, a major challenge exists to decipher the spatiotemporal epigenetic and transcriptional

Pseudouridine is the most prevalent RNA modification, and its aberrant function is implicated in various human diseases. However, the specific impact of pseudouridylation on hematopoiesis remains poorly understood. Here, we investigated the role of transfer RNA (tRNA) pseudouridylation in erythropoiesis and its association with mitochondrial myopathy, lactic acidosis, and sideroblastic anemia syndrome

Multiple myeloma is characterized by a huge heterogeneity at the molecular level. The pathway is the most frequently mutated, in ∼50% of the patients. However, these mutations are frequently subclonal, suggesting a secondary event. Because these genes are part of our routine next-generation sequencing panel, we analyzed >10 000 patients with different plasma cell disorders to describe the landscape

Secondary kinase domain mutations in BCR::ABL1 represent the most common cause of resistance to tyrosine kinase inhibitor (TKI) therapy in patients with chronic myeloid leukemia. The first 5 approved BCR::ABL1 TKIs target the adenosine triphosphate (ATP)–binding pocket. Mutations confer resistance to these ATP-competitive TKIs and those approved for other malignancies by decreasing TKI affinity and/or

We evaluated the cost-effectiveness of prophylaxis with recombinant von Willebrand factor (rVWF) vs with plasma-derived von Willebrand factor (pdVWF) for patients with severe Von Willebrand disease. We found that rVWF is a cost-saving factor replacement compared with pdVWF across all willingness-to-pay thresholds in the United States.

Lysyl oxidase (LOX) is a facilitator of extracellular matrix cross-linking. Using newly developed megakaryocyte-specific LOX knockout mice, we show that LOX expressed in these scarce bone marrow cells affects bone volume and collagen architecture in a sex-dependent manner.

Diffuse large B-cell lymphoma (DLBCL) encompasses a diverse spectrum of aggressive B-cell lymphomas with remarkable genetic heterogeneity and myriad clinical presentations. Multiplatform genomic analyses of DLBCL have identified oncogenic drivers within genetic subtypes that allow for pathologic subclassification of tumors into discrete entities with shared immunophenotypic, genetic, and clinical features

Timely diagnosis of systemic mastocytosis (SM) remains challenging because of care heterogeneity. We implemented a standardized approach for SM screening and diagnosis using a novel health care system–wide international screening registry. A retrospective analysis assessed rates of SM, cutaneous mastocytosis (CM), and molecular diagnoses before and 2 years after care standardization. The accuracy of

Axicabtagene ciloleucel (axi-cel) is an autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy approved for relapsed/refractory (R/R) large B-cell lymphoma (LBCL). Despite extensive data supporting its use, outcomes stratified by race and ethnicity groups are limited. Here, we report clinical outcomes with axi-cel in patients with R/R LBCL by race and ethnicity in both real-world and clinical

Human herpesvirus 6B (HHV-6B) reactivation and disease are increasingly reported after chimeric antigen receptor (CAR) T-cell therapy (CARTx). HHV-6 reactivation in the CAR T-cell product was recently reported, raising questions about product and patient management. Because of overlapping manifestations with immune effector cell–associated neurotoxicity syndrome, diagnosing HHV-6B encephalitis is challenging

Factor X (FX) deficiency is a rare bleeding disorder manifesting a bleeding tendency caused by low FX activity levels. We aim to explore the use of fitusiran (an investigational small interfering RNA that silences antithrombin expression) to increase thrombin generation and the in vivo hemostatic potential under conditions of FX deficiency. We therefore developed a novel model of inducible FX deficiency

We evaluated the chronic lymphocytic leukemia International Prognostic Index (CLL-IPI) in patients with CLL treated first line with targeted drugs (n = 991) or chemoimmunotherapy (n = 1256). With a median observation time of 40.5 months, the 3-year progression-free survival (PFS) rates for targeted drug–treated patients varied by CLL-IPI risk group: 96.5% (low), 87.6% (intermediate), 82.4% (high),

The phase 2 CLL2-BAAG trial tested the measurable residual disease (MRD)–guided triple combination of acalabrutinib, venetoclax, and obinutuzumab after optional bendamustine debulking in 45 patients with relapsed/refractory chronic lymphocytic leukemia (CLL). MRD was measured by flow cytometry (FCM; undetectable MRD <10) in peripheral blood (PB) and circulating tumor DNA (ctDNA) using digital droplet

SRY-related HMG-box gene 11 (SOX11) is a transcription factor overexpressed in mantle cell lymphoma (MCL), a subset of Burkitt lymphomas (BL) and precursor lymphoid cell neoplasms but is absent in normal B cells and other B-cell lymphomas. SOX11 has an oncogenic role in MCL but its contribution to BL pathogenesis remains uncertain. Here, we observed that the presence of Epstein-Barr virus (EBV) and

Inflammatory responses must be tightly coordinated with the activation of emergency myelopoiesis to produce potent myeloid cells that fight infection without causing excessive host damage. Here, we show that granulocyte-macrophage colony stimulating factor (GM-CSF) programs myeloid-committed progenitors to produce trained macrophages (increased cytokine response), but programs the upstream noncommitted