Immune checkpoint blockade resistance narrows the efficacy of cancer immunotherapies, but the underlying mechanism remains elusive. Delineating the inherent mechanisms of anti-PD1 resistance is important to improve outcome of patients with advanced HCC. The level of cricTMEM181 was measured in HCC patients with anti-PD1 therapy by RNA sequencing and then confirmed by qPCR and Sanger sequencing. Immune

The Mayo-2018 smoldering multiple myeloma (SMM) risk score is used routinely in the clinical setting but has only been validated at diagnosis. In SMM patients, the progression risk decreases over time. However, the utility of applying risk stratification models after diagnosis is unknown. We retrospectively studied 704 SMM patients and applied the Mayo 2018 and IMWG-2020 risk stratification models

Thromboses are prevalent in POEMS syndrome, but few risk factors for POEMS-associated thrombosis have been identified. The objective of this study is to identify novel risk factors for POEMS-associated thrombosis. In this retrospective cohort of 230 POEMS patients, 27% developed thrombosis. Arterial events were slightly more common than venous. Stroke accounted for 26% of all thromboses and 53% of

Preclinical studies have demonstrated activity of the oral proteasome inhibitor (PI) ixazomib (IXA) in bortezomib-resistant multiple myeloma (MM) and synergy with immunomodulatory drugs. We therefore conducted a phase I/II study to establish the safety and preliminary efficacy of IXA with pomalidomide (POM) and dexamethasone (DEX) in lenalidomide (LEN)/PI-refractory MM. Dose escalation established

Langerhans cell histiocytosis (LCH) is a histiocytic neoplasm that can involve the lungs as single system (LCH-SSL) or multisystem disease (LCH-MSL). The role of full-body radiographic staging to determine whether patients have LCH-SSL or LCH-MSL is unclear. Long-term outcomes of LCH-SSL versus LCH-MSL and multisystem without lung involvement (LCH-MSNL) are unknown. A retrospective study of adult LCH

Spur cell hemolytic anemia (SCHA) is a rare, acquired, nonimmune hemolytic anemia of decompensated cirrhosis. Data describing prognostic impact, outcomes of liver transplant, and clinical hematologic characteristics of SCHA are absent or limited. We performed a multicenter, 24-year observational cohort study of patients with SCHA, retrospectively analyzing hepatic and hematologic parameters, independent

Athletes abuse recombinant human erythropoietin (rhEPO) and erythropoiesis stimulating agents to increase hemoglobin mass and improve performance. To evade detection, athletes have developed sophisticated blood doping regimens, which often include rhEPO micro-dosing. Detection of these methods requires biomarkers with increased sensitivity and a sample matrix that is more amenable to frequent testing

The six-minute walk test (6MWT) has been used in patients with sickle cell disease (SCD), in conjunction with tricuspid regurgitant velocity (TRV) and plasma N-terminal pro-brain natriuretic peptide (NT-pro BNP), to assess risk of having pulmonary hypertension. Exercise-induced vital sign changes (VSCs) are predictors of clinical outcomes in other diseases. In this study, we assess the predictors and

Erythropoiesis-stimulating agents (ESA) are effective for chemotherapy-induced anemia (CIA) but associated with serious adverse events. Safer alternatives would be beneficial in this population. The efficacy and safety of ferric carboxymaltose (FCM) as monotherapy for CIA was evaluated. This Phase 3, 18-week, double-blind, placebo-controlled study randomized adults with ≥ 4 weeks of chemotherapy remaining

We describe presenting features, treatment strategies, and follow-up events involving 41 patients (median age 39 years, range 1–81; 54% males) with high oxygen affinity (HOA) hemoglobinopathy-associated erythrocytosis, seen at our institution (1973–2020). Thirty-four (83%) patients carried β-chain (13 Malmo, 4 Olympia, 3 San Diego, 2 Wood) and 7 (17%) α-chain (4 Dallas and one each Columbia-Missouri

Chronic lymphocytic leukemia (CLL) is one of the most frequent types of leukemia. It typically occurs in elderly patients and has a highly variable clinical course. Leukemic transformation is initiated by specific genomic alterations that interfere with the regulation of proliferation and of apoptosis in clonal B-cells.

Low oxygen affinity hemoglobin (Hb) mutations are a rare but important consideration in patients presenting with low peripheral oxygen saturations (SpO2) and anemia without clinical evidence of hypoxia; cyanosis may also be present. Hb mutations that affect oxygen affinity alter critical molecular regions involved in the conformational transition between the relaxed (R) oxygenated, and the tense (T)

Contemporary, population-based, cause-specific mortality risks within the heterogeneous subtypes of classical myeloproliferative neoplasms (MPNs)–polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF)–in the United States are needed to inform patient care. Therefore, we leveraged MPN cases diagnosed in the surveillance, epidemiology, and end results (SEER) Program in

Multiple myeloma (MM) disproportionately affects Blacks compared to individuals belonging to other racial groups.1 Since the introduction of novel anti-myeloma agents, multiple studies have found disparate survival outcomes among Black patients compared to White MM patients.2, 3 Limited access to novel therapies and autologous hematopoietic cell transplantation (auto-HCT) has been considered partly

With the introduction of targeted agents into the treatment paradigm of chronic lymphocytic leukemia (CLL), outcomes for patients have markedly improved. With prolonged overall survival in the predominantly elderly population of CLL patients, second primary malignancies (SPM) become more relevant as competing causes of death. Prior analyses have consistently shown increased rates of SPM in patients

Acute graft-versus-host disease (aGvHD), together with infections, constitute the two main early complications of allogeneic hematopoietic cell transplantation (alloHCT).1 The mainstay of first-line therapy in aGvHD is systemic administration of high-dose glucocorticoids, but only 40%–60% of patients respond to this treatment depending on the grade of severity of the disease.1 At present, there is

Polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF) are BCR/ABL1-(Philadelphia chromosome [Ph−]) negative myeloproliferative neoplasms (MPNs).1 Mutations of Janus Kinase 2 (JAK2), calreticulin (CALR), and myeloproliferative leukemia virus oncogene (MPL) are implicated in these MPNs, leading to clonal hematopoietic stem cell proliferation.1 The most dreaded complication

Coagulopathy and intravascular thrombosis are known complications of SARS-CoV-2 infection. The pathomechanism of COVID-19-associated micro- and macrovascular thrombosis likely involves the interplay of the coronavirus with endothelial cells, platelets, and immune cells.1 Activation of endothelial cells and platelets results in procoagulant imbalance and macrovascular thrombotic events that are associated

The association between immune thrombocytopenia (ITP) and the Covid-19 vaccine drew national attention when The New York Times reported in January 2021 that a Florida physician died from a hemorrhagic stroke after developing ITP within 2 weeks of vaccination.1 Shortly thereafter, a review of the Vaccine Adverse Event Reporting System database described 20 cases of Covid-19 vaccine-associated thrombocytopenia

To The Editor: SARS-CoV-2 (COVID-19) is a life-threatening disease that has rapidly spread around the world, reaching a mortality rate of > 4.7 million. Cancer patients are at increased risk of COVID-19 complications, and those with hematological malignancies have a more severe infection course than patients with solid tumors. Among hospitalized COVID-19 patients, those with blood cancer have a 2-fold

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Von Willebrand Factor (VWF) and Factor VIII (FVIII) circulate in a noncovalent complex in blood and promote primary haemostasis and clotting respectively. A new VWF A1-domain binding aptamer, BT200, demonstrated good subcutaneous bioavailability and a long half-life in non-human primates. This first-in-human, randomised, placebo-controlled, double-blind trial tested the hypothesis that BT200 is well

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The anti-apoptotic protein B-cell lymphoma 2 (BCL-2) is a key regulator of the intrinsic apoptotic pathway,1 and survival dependence on BCL-2 has been demonstrated in chronic lymphocytic leukemia (CLL).2 Venetoclax is a highly selective, potent, orally bioavailable BCL-2 inhibitor3 that has demonstrated efficacy as monotherapy for patients with previously treated CLL in four clinical studies.4-8 Because

Hematopoietic stem cell transplantation (HSCT) offers the highest possible curative potential for patients with hematological malignancies. However, the management of post-transplant relapse remains a challenging task. In general, the prognosis of patients with post-transplant relapse is extremely poor, since many of them cannot tolerate or are refractory to commonly used approaches. In view of this

Transfusion of red blood cells (RBCs) is a life-saving intervention for anemic patients. Human induced pluripotent stem cells (iPSC) have the capability to expand and differentiate into RBCs (iPSC-RBCs). Here we developed a murine model to investigate the in vivo properties of human iPSC-RBCs. iPSC lines were produced from human peripheral blood mononuclear cells by transient expression of plasmids

Antithrombin deficiency, the most severe thrombophilia, might be underestimated, since it is only investigated in cases with consistent functional deficiency or family history. We have analyzed 444 consecutive, unrelated cases, from 1998 to 2021, with functional results supporting antithrombin deficiency in at least one sample. Plasma antithrombin was evaluated by functional and biochemical methods

Systemic light chain (AL) amyloidosis is caused by a usually small plasma cell clone that produces amyloidogenic immunoglobulin light chains. This clone may affect immune competence and immune system fitness but, in addition, organ dysfunction, leading to heart failure, nephrotic range proteinuria, malabsorption, etc. further increases susceptibility to infections and risk of complications. Anti-plasma

Cord blood transplantation (CBT) is an alternative donor transplantation method and has the advantages of rapid availability and the possibility of inducing a more potent graft-versus-leukemia effect, leading to a lower relapse rate for patients with non-remission relapse and refractory acute myeloid leukemia (R/R AML). This study aimed to investigate the impact of CBT, compared to human leukocyte

Adult T-cell leukemia/lymphoma (ATLL) is an aggressive T-cell malignancy with a poor prognosis with current therapy. Here we report genome-wide CRISPR-Cas9 screening of ATLL models, which identified CDK6, CCND2, BATF3, JUNB, STAT3, and IL10RB as genes that are essential for the proliferation and/or survival of ATLL cells. As a single agent, the CDK6 inhibitor palbociclib induced cell cycle arrest and

Adult Langerhans cell histiocytosis (LCH) remains poorly defined. We retrospectively studied 266 newly diagnosed LCH patients to understand the clinical presentation, treatment, and prognosis of adult LCH. The median age at diagnosis was 32 years (range, 18–79 years). At the time of diagnosis, 40 patients had single lesions within a single system, 18 patients had single pulmonary LCH, 26 patients had

The Nobel Prize in Physiology or Medicine 2021 was awarded jointly to David Julius and Ardem Patapoutian for their discoveries of receptors for temperature and touch. David Julius, Professor of Physiology at UCSF, studied mechanisms by which we sense heat, cold, and chemical irritants. Julius and colleagues developed a novel genome-wide screen for elevations in intracellular [Ca2+] in response to chemicals

Although chimeric antigen receptor T cells demonstrated remarkable efficacy in patients with chemo-resistant hematologic malignancies, a significant portion still resist or relapse. This immune evasion may be due to CAR T cells dysfunction, a hostile tumor microenvironment, or resistant cancer cells. Here, we review the intrinsic resistance mechanisms of cancer cells to CAR T cell therapy and potential

The newly identified thirteen-series Resolvins (RvTs) regulate phagocyte functions and accelerate resolution of infectious inflammation. Since SARS-CoV-2 elicits uncontrolled inflammation involving neutrophil extracellular traps (NETs), we tested whether stereochemically defined RvTs regulate NET formation. Using microfluidic devices capturing NETs in PMA-stimulated human whole blood, the RvTs, RvT1-RvT4

STAT proteins represent an important family of evolutionarily conserved transcription factors that play key roles in diverse biological processes, notably including blood and immune cell development and function. Classically, STAT proteins have been viewed as inducible activators of transcription that mediate cellular responses to extracellular signals, particularly cytokines. In this ‘canonical’ paradigm

Cancer will soon become the leading cause of death in every country in the twenty-first century. This study aimed to analyze the mortality and morbidity of 29 types of cancer in 204 countries or regions from 1990 to 2019 to guide global cancer prevention and control. Detailed information for 29 cancer groups was collected from the Global Burden of Disease Study in 2019. The age-standardized incidence

We describe a 70-year-old woman with stage IV diffuse large B-cell lymphoma, not otherwise specified (activated B-cell subtype, non-BCL2/MYC double expressor) treated from May to October 2019 on the phase III POLARIX trial (polatuzumab vedotin plus R-CHP versus R-CHOP), who was subsequently in remission. In December 2020, she developed dyspnea, fever, and cough, eventually testing positive for SARS-CoV-2

Allogeneic hematopoietic stem cell transplantation (HSCT) is a curative option for many hematologic conditions and is associated with considerable morbidity and mortality. Therefore, prognostic tools are essential to navigate the complex patient, disease, donor, and transplant characteristics that differentially influence outcomes. We developed a novel, comprehensive composite prognostic tool. Using