The advent of reduced-intensity conditioning regimens, improvements in graft-versus-host disease prophylaxis, and better supportive care have permitted increasing use of allogeneic hematopoietic cell transplantation (allo-HCT) in adults age ≥70 with AML. However, while potentially curative, non-relapse mortality and relapse represent the main causes of treatment failure, highlighting the importance

Engineered cellular therapy with CD19-targeting chimeric antigen receptor T-cells (CAR-T) has revolutionized outcomes for patients with relapsed/refractory Large B-Cell Lymphoma (LBCL), but the cellular and molecular features associated with response remain largely unresolved. We analyzed serial peripheral blood samples ranging from day of apheresis (day -28/baseline) to 28 days after CAR-T infusion

Despite advances in the treatment paradigm of patients with acute myeloid leukemia (AML), TP53 mutated AML represents a molecular subgroup that has failed to improve with an overall survival around 6 months that is independent of age and fitness. Notably, there has been significant elucidation in understanding the biology of the disease and key advancements in the classification and prognostication

Although complete remission rates in adults with B-cell precursor acute lymphoblastic leukemia (BCP-ALL) have improved over the last two decades, it is still inferior to that of the pediatric population and once in remission, the risk of relapse is still high. Furthermore, while pediatric-inspired chemotherapy regimens have improved long-term outcomes for adolescents and young adults, these intensive

Chimeric antigen receptor (CAR) T-cell therapy has revolutionized the treatment of patients with relapsed or refractory hematologic malignancies, but it comes with unique toxicities, notably cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). As experience with CAR T-cell therapy grows, distinct and infrequent neurological complications are becoming increasingly

Peripheral T-cell lymphomas (PTCLs) encompass a heterogeneous group of post-thymic T-cell lymphomas with more than 30 distinct subtypes associated with varied clinicopathological features. Unfortunately, the overall survival of the major PTCL subtypes is dismal and has not improved for decades, thus there is an urgent unmet clinical need to improve diagnosis, therapies, and clinical outcomes. The diagnosis

Venous thromboembolism (VTE) is a common complication in patients with brain tumors. The management of acute VTE is particularly challenging due to an elevated risk of intracranial hemorrhage (ICH). Risk for developing ICH on anticoagulation is influenced by a number of factors including tumor type, recent surgery, concomitant medications, platelet counts, and radiographic features. In patients with

Outcomes are poor in triple-class-exposed (TCE) relapsed/refractory multiple myeloma (RRMM). In the phase 3 KarMMa-3 (clinicaltrials.gov; NCT03651128) trial, patients with TCE RRMM and 2-4 prior regimens were randomized 2:1 to idecabtagene vicleucel (ide-cel) or standard regimens (SRs). An interim analysis (IA) demonstrated significantly longer median progression-free survival (PFS; primary endpoint;

We performed an international retrospective cohort study to investigate the prognostic impact of cytogenetic abnormalities by FISH in 283 patients with AL amyloidosis treated with frontline daratumumab-bortezomib-cyclophosphamide-dexamethasone (Dara-VCD) or Dara-VD. The cytogenetic subgroups of interest were t(11;14), gain/amp(1q) [hereafter, +1q], hyperdiploidy, deletion(13q), del(17p), and myeloma

Using nanopore sequencing, we showed feasibility and impact of rapid genomic screening for managing thrombotic microangiopathies (TMAs) in 18 prospective cases, achieving diagnoses in less than three days. We compared results to standard exome sequencing, cost-efficiency and complement blockade initiation.

Immune thrombocytopenia (ITP) is a complicated bleeding disease characterized by sharp platelet reduction. As a dominating element involved in ITP, megakaryocytes (MKs) are responsible for thrombopoiesis. However, the mechanism underlying the dysregulation of thrombopoiesis that occurs in ITP remains unidentified. In this study, we examined the role of yes-associated protein 1 (YAP1) in thrombopoiesis

Hemostatic imbalances are frequent in patients with cancer. While cancer-associated thrombotic complications have been well characterized, data on bleeding events in cancer patients are sparse. Therefore, we aimed to investigate the incidence, risk factors, and impact on prognosis of bleeding events in cancer patients initiating systemic anti-cancer therapies in a prospective cohort study, the Vienna

The association between antimetabolite dose intensity (DI) and adverse events among children receiving maintenance therapy for acute lymphoblastic leukemia (ALL) remains unclear, especially in context of antimetabolite adherence. Using COG-AALL03N1 data, we examined the association between high DI during the first four study months and (i) treatment-related toxicities during the subsequent two study

Hemophagocytic lymphohistiocytosis (HLH) is a hyperinflammatory disorder driven by interferon-gamma (IFN-γ). Emapalumab, an anti-IFN-γ antibody, is approved for the treatment of patients with primary HLH. Hematopoietic stem cell transplantation (HSCT) is required for cure of HLH. Reduced intensity conditioning (RIC) HSCT is associated with improved survival but higher incidences of mixed chimerism

Platelets contribute to a variety of physiological processes including inflammation, sepsis and cancer. However, due to their primary role in hemostasis, platelet transfusions are largely restricted to managing thrombocytopenia and bleeding. One way to expand the utility of platelet transfusions would be to genetically engineer donor platelets with new or enhanced functions. We have previously shown

Sickle cell disease (SCD) is canonically characterized by reduced red blood cell (RBC) deformability, leading to microvascular obstruction and inflammation. Although the biophysical properties of sickle RBCs are known to influence SCD vasculopathy, the contribution of poor RBC deformability to endothelial dysfunction has yet to be fully explored. Leveraging interrelated in vitro and in silico approaches

Extramedullary disease (EMD) is a high-risk feature of multiple myeloma (MM) and remains a poor prognostic factor, even in the era of novel immunotherapies. Here, we applied spatial transcriptomics (-seq [n = 2] and 10X Visium [n = 12]) and single-cell RNA sequencing (n = 3) to a set of 14 EMD biopsies to dissect the 3-dimensional architecture of tumor cells and their microenvironment. Overall, infiltrating

Anti-D can occur in D-positive patients who inherit genetic variants encoding partial D antigen expression, but unexpected anti-D is also found in the plasma of patients with sickle cell disease who have conventional gene(s) and are transfused with units from Black donors. These anti-D are likely stimulated by variant Rh expressed on donor cells; however, patients with anti-D, regardless of cause,

Teclistamab is a B-cell maturation antigen (BCMA)–directed bispecific antibody approved for the treatment of patients with triple-class exposed relapsed/refractory multiple myeloma (R/RMM). In the phase 1/2 MajesTEC-1 study, a cohort of patients who had prior BCMA-targeted therapy (antibody-drug conjugate [ADC] or chimeric antigen receptor T-cell [CAR-T] therapy) was enrolled to explore teclistamab

The Philadelphia (Ph) chromosome is 1 of the few genetic aberrations in which a casualty has been proven and, as such, represents a success in the history of medicine. This is also evident in the setting of Ph acute lymphoblastic leukemia (ALL), the most frequent genetic subgroup in adult ALL, whose incidence increases with age and whose prognosis, before the advent of tyrosine kinase inhibitors (TKIs)

Variant Creutzfeldt-Jakob disease (vCJD) is a devastating disease caused by transmission of bovine spongiform encephalopathy to humans. Although vCJD cases are now rare, evidence from appendix surveys suggests that a small proportion of the United Kingdom population may be infected without showing signs of disease. These “silent” carriers could present a risk of iatrogenic vCJD transmission through

The ultimate goal of bringing most new drugs to the clinic in hematological malignancy is to improve overall survival. However, the use of surrogate endpoints for overall survival is increasingly considered standard practice, since a well validated surrogate endpoint can accelerate the outcome assessment and facilitate better clinical trial design. Established examples include monitoring minimal residual

Loss of endothelial barrier function contributes to the pathophysiology of many inflammatory diseases. Coagulation factor XI (FXI) plays a regulatory role in inflammation. Although activation of FXI increases vascular permeability in vivo, the mechanism by which FXI or its activated form FXIa disrupts endothelial barrier function is unknown. We investigated the role of FXIa in human umbilical vein

Patients with relapsed/refractory acute lymphoblastic leukemia (ALL) or lymphoblastic lymphoma (LL) have poor outcomes compared with newly diagnosed, treatment-naïve patients. The phase 2, open-label DELPHINUS study evaluated daratumumab (16 mg/kg IV) plus backbone chemotherapy in children with relapsed/refractory B-cell ALL (n = 7) after ≥2 relapses, and children and young adults with T-cell ALL (children

Menin inhibitors that disrupt the menin-MLL interaction hold promise for treating specific acute myeloid leukemia (AML) subtypes, including KMT2A rearrangements (KMT2A-r), yet resistance remains a challenge. Here, through systematic chromatin-focused CRISPR screens, along with genetic, epigenetic, and pharmacologic studies in a variety of human and mouse KMT2A-r AML models, we uncovered a potential

Multiple myeloma (MM) is an incurable malignancy characterized by altered expression of coding and noncoding genes promoting tumor growth and drug resistance. Although the crucial role of long noncoding RNAs (lncRNAs) in MM is clearly established, the function of the noncoding RNAome, which might allow the design of novel therapeutics, is largely unknown. We performed an unbiased CRISPR-Cas9 loss-of-function

The microbiota, comprising bacteria, fungi, and viruses residing within our bodies, functions as a key modulator in host health and states, including immune responses. Studies have linked microbiota and microbiota-derived metabolites to immune cell functions. In this review, we probe the complex relationship between the human microbiota and clinical outcomes of cellular therapies that leverage immune

The genetic background of the high prevalence red blood cell antigen AnWj has remained unresolved since its identification in 1972, despite reported associations with both CD44 and Smyd1 histone methyltransferase. Development of anti-AnWj, which may be clinically significant, is usually due to transient suppression of antigen expression, but a small number of individuals with persistent, autosomally-recessive

In the context of healthcare, intersectionality refers to a framework that focuses on the ways multiple axes of social inequality intersect and compound at the macro and micro levels to produce a broad range of unequal health outcomes. With the aid of tools such as the wheel of power and privilege, this framework can help identify systemic biases hidden in plain sight in the routine diagnostic, therapeutic

The European LeukemiaNet (ELN) genetic risk classifications were developed based on data from younger adults receiving intensive chemotherapy. Emerging analyses from patients receiving less-intensive therapies prompted a proposal for an ELN genetic risk classification specifically for this patient population.

Fluorescence in situ hybridization (FISH) using break-apart probes is recommended for identifying high-grade B-cell lymphoma with and rearrangements (HGBCL-DH-). Unbalanced break-apart patterns, in which the red or green signal is lost, are commonly reported as an equivocal result by clinical laboratories. In a cohort of 297 HGBCL-DH-, 13% of tumors had unbalanced break-apart patterns with loss of

The European LeukemiaNet (ELN) acute myeloid leukemia (AML) genetic risk classification systems are based on response to intensive chemotherapy; their ability to discriminate outcomes in older patients treated with venetoclax-azacitidine may be suboptimal. This pooled analysis of the phase 3 VIALE-A trial (NCT02993523) and phase 1b study (NCT02203773) examined prognostic stratification according to

With emerging new drugs in myelofibrosis (MF), a robust and harmonized framework for defining the severity of anemia and response to treatment will enhance clinical investigation and facilitate interstudy comparisons. Accordingly, the lead authors on the 2013 edition of the International Working Group–European LeukemiaNet (IWG-ELN) response criteria in MF were summoned to revise their document with

HLA-DP permissive mismatches can be assigned a direction according to their immunopeptidome divergence across core and noncore subsets. Noncore permissive graft-versus-host mismatches show significantly reduced risks of relapse without increased nonrelapse mortality compared with allele-matched pairs.