In retrospective studies, autologous stem cell transplantation (ASCT) conditioning with intravenous busulfan and melphalan (BUMEL) led to longer progression-free survival (PFS) than melphalan alone (MEL200). We compared BUMEL vs. MEL200 outcomes in newly diagnosed multiple myeloma (NDMM) patients receiving intensified bortezomib, lenalidomide and dexamethasone (VRD) induction and consolidation therapy

Anemia of inflammation (AI) is the second most common form of anemia and is prevalent in patients with chronic inflammatory states, such as infection, autoimmunity, and cancer. Interleukin 6 (IL6) is well-known to induce the iron-sequestering hormone hepcidin, which results in iron-restricted anemia. The contributions of other pro-inflammatory cytokines such as tumor necrosis factor-α (TNFα) and interferon-γ

Blood transfusions save millions of lives worldwide each year, yet formation of antibodies against non-self antigens remains a significant problem, particularly in frequently transfused patients. We designed and tested the Universal Blood Donor Typing (UBDT_PC1) array for automated high-throughput simultaneous typing of human erythroid, platelet, leukocyte, and neutrophil antigens (HEA, HPA, HLA, and

Clonal hematopoiesis of indeterminate potential (CHIP) is associated with increased mortality and malignancy risk, yet the determinants of clonal expansion remain poorly understood. We performed sequencing at >4,000x depth of coverage for CHIP mutations in 6,976 postmenopausal women from the Women's Health Initiative at two timepoints: the WHI baseline exam and approximately 16 years later at the Long

Patients with follicular lymphoma (FL) who experience disease progression within 24 months of diagnosis (POD24) have a lower survival. Positron emission tomography (PET) response and circulating tumor DNA (ctDNA) residual disease (MRD) assessment at end of induction therapy (EOI) may allow their early identification. A representative cohort of 141 patients from the RELEVANCE phase III trial with both

Cellular therapies targeting B-cell maturation antigen have shown promise in controlled clinical trials, but their impact in broader, diverse patient populations remains underexplored. This study examines the real-world efficacy and safety in 343 triple-class exposed patients with relapsed and refractory multiple myeloma (RRMM) who received idecabtagene vicleucel (ide-cel, n=266) or ciltacabtagene

Rapid CD137 upregulation on alloreactive T-cells upon allogeneic stimulation suggests that their selective elimination could prevent acute graft-versus-host disease (aGVHD) after allogeneic hematopoietic stem cell transplantation (HCT). Here, we developed a novel aGVHD prophylactic regimen consisting of a single dose of an anti-CD137 antibody-drug conjugate (CD137-ADC) administered on the day of transplant

CD19-directed chimeric antigen receptor (CAR) T-cell therapy has revolutionized the treatment of relapsed/refractory B-cell non-Hodgkin lymphoma (B-NHL) and recently showed effects in autoimmune diseases such as systemic lupus erythematosus (SLE). Despite high levels of inflammation, toxicity appeared to differ in SLE and B-NHL. We therefore compared CAR T-cell kinetics and treatment-related side-effects

An acute inflammatory response to infection or sterile injury involves an adequate activation and recruitment of leukocytes. Activation of β2-integrins is required for neutrophil recruitment and is also mandatory for various neutrophil cell-intrinsic functions. GTPases are key regulators of the actin cytoskeleton and are required for β2-integrin activation. MyosinIXb (Myo9b), a Rho GTPase-activating

Although allogeneic HCT is a leading treatment approach for myeloid malignancies, challenges in its immune biology and in treatment approaches remain. In the past decade major advances in the knowledge of mechanisms of graft-versus host disease (GvHD) has allowed development of new treatments both for GvHD prophylaxis and treatment. However, although successes did occur, failure did as well. Reasons

Disease response and progression assessment in multiple myeloma (MM) is based on various measurements of monoclonal protein (serum and urine protein electrophoresis, serum free light chain (FLC, and or quantitative immunoglobulins). Currently, the IMWG consensus response criteria require two sequential assessments of any one marker made at any time before confirmation of disease progression and the

AL amyloidosis is a disorder characterized by expansion of clonal plasma cells in the bone marrow and distant end organ damage mediated by misfolded immunoglobulin free light chains. There are currently limited data regarding the functional characteristics of AL amyloidosis plasma cells and their surrounding bone marrow microenvironment. We performed 5' single cell RNA sequencing on newly diagnosed

Monoclonal antibodies targeting CD38 are a therapeutic mainstay in multiple myeloma (MM). While they have contributed to improved outcomes, most patients still experience disease relapse, and little is known about tumor-intrinsic mechanisms of resistance to these drugs. Antigen escape has been implicated as a mechanism of tumor cell evasion in immunotherapy. Yet, it is unknown whether MM cells can

TET2 is among the most commonly mutated genes in both clonal hematopoiesis and myeloid malignancies, thus, the ability to identify selective dependencies in TET2 deficient cells has broad translational significance. Here, we identify regulators of Tet2 knockout (KO) hematopoietic stem and progenitor cell (HSPC) expansion using an in vivo CRISPR-Cas9 KO screen, in which nucleotide barcoding enabled

Developing anti-FVIII inhibitory antibodies (inhibitors) is a significant complication of FVIII protein replacement therapy in hemophilia A. Our previous study demonstrated that follicular helper T (TFH) cells play a critical role in FVIII inhibitor development. Follicular regulatory T (TFR) cells are a subset of Foxp3+ T cells recently identified in the germinal center that can modulate TFH cell activation

The human genome contains regulatory DNA elements, known as enhancers, that can activate gene transcription over long chromosomal distances. Here, we showed that enhancer distance can be critical for gene silencing. We demonstrated that linear recruitment of the normally distal strong HBB enhancer to developmentally silenced embryonic HBE or fetal HBG promoters through deletion or inversion of intervening

Chronic lymphocytic leukemia (CLL) is a disease of great clinical and biologic heterogeneity; some patients are observed for years without symptoms, whereas others rapidly develop progressive disease requiring treatment. With therapy, some patients eventually develop resistant CLL or transformation to an aggressive form. Across this spectrum, patients experience immune dysfunction associated with increased

Relapsed/refractory T-cell acute lymphoblastic leukemia (ALL; T-ALL)/lymphoma (LBL) represent a significant unmet medical need. WU-CART-007 is a CD7-targeting, allogeneic, fratricide-resistant chimeric antigen receptor T-cell product generated from healthy donor T cells. WU-CART-007 was evaluated in a phase 1/2 study with a 3+3 dose-escalation design followed by cohort expansion in relapsed/refractory

The integrity of the hematopoietic stem cell (HSC) pool depends on effective long-term self-renewal and the timely elimination of damaged or differentiation-prone HSCs. Although the protein kinase R–like endoplasmic reticulum kinase (PERK) branch of the unfolded protein response has been shown to initiate proapoptotic signaling in response to endoplasmic reticulum (ER) stress in vitro, its role in

Acute megakaryoblastic leukemia (AMKL) that is driven by the RBM15-MKL1 fusion protein (RM-AMKL) is encoded by the recurrent t(1;22) translocation. Dysregulation of the N6-methyladenosine (m6A) modification affects RNA fate and is linked to oncogenesis. Because RBM15 is critical for bringing the m6A writer complex to specific RNAs, we hypothesized that RM disrupts the m6A modification, thereby altering

The continuous improvement in progression-free survival (PFS) of patients with multiple myeloma (MM) raises interest in evaluating peripheral residual disease (PRD) toward more frequent readouts of tumor kinetics while preserving quality of life. Here, we present BloodFlow, a new method that combines immunomagnetic enrichment of CD138+ circulating plasma cells in peripheral blood (PB) with next-generation

Most calreticulin (CALR) mutations in myeloproliferative neoplasms are classified as either type 1, a 52–base pair deletion (CALRdel52); or type 2, a 5–base pair insertion (CALRins5). Both are gain-of-function (GOF) mutations that generate an identical mutant C-terminal tail, which mediates the binding to, and activation of, the thrombopoietin receptor myeloproliferative leukemia protein (MPL). We

Suppression of plasminogen activation and/or plasmin activity (PA) reduces blood loss and decreases hemorrhage-related death. However, whether the endogenous PA system is a biological mechanism to prevent intravascular thrombus formation is debated, and the potential that reduced PA may increase venous thrombosis/thromboembolism (VTE) risk cautions against the use of antifibrinolytic agents. We aimed

Early recognition and treatment of heparin-induced thrombocytopenia (HIT) are crucial to prevent severe complications. Although immunoassays offer rapid diagnosis, their sensitivity and specificity are suboptimal. Sequential combinations of quantitative immunoassay results improve their diagnostic accuracy. We aimed to validate 2 Bayesian approaches combining 2 rapid immunoassays and to compare their

Long noncoding RNAs (lncRNAs) are a significant yet largely uncharted component of the cancer transcriptome, with their isoform-specific functions remaining poorly understood. In this study, we used RNA-targeting CRISPR-Cas13d to uncover and characterize hundreds of tumor-essential lncRNA (te-lncRNA) isoforms with clinical relevance. Focusing on multiple myeloma (MM), we targeted the lncRNA transcriptome

The autoimmune response driving hematopoietic stem and progenitor cell (HSPC) destruction in immune-mediated aplastic anemia (AA) remains incompletely understood. We previously identified a disease-specific immune cell network involving T, B, and myeloid cells. However, the interactions within this network, the interaction with the microenvironment, and the chronological events in AA development, remain