Blood Advances

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Few patients with non-favorable risk (NFR) acute leukemia and MDS (AL/MDS) have historically accessed allogeneic transplantation (HCT). We assessed whether this can be improved by the integration of HCT/leukemia care and use of haploidentical donors (HID). Of 256 consecutive patients aged ≤75 who received initial therapy at our center for NFR AL/MDS from 2016 to 2021, 147 (57%) proceeded to planned HCT (70% for patients aged <60). On logistic regression analysis, age (OR 1.50 per 10-year increment, p<0...

Changes in surface glycan determinants, specifically sialic acid loss, determine platelet life span. The gradual loss of stored platelet quality is a complex process that fundamentally involves carbohydrate structures. Here, we applied lipophilic extraction and glycan release protocols to sequentially profile N- and O-linked glycans in freshly isolated and seven-day room temperature stored platelet concentrates. Analytical methods including matrix assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS), tandem mass spectrometry (MSn), and liquid chromatography (LC) were used to obtain structural details of selected glycans and terminal epitopes...

Utilising tissue whole exome sequencing (WES) and circulating tumor cell-free DNA (ctDNA), this Australasian Leukaemia & Lymphoma Group (ALLG) translational study sought to characterise primary and acquired molecular determinants of response and resistance of MZL to zanubrutinib for patients treated on the MAGNOLIA clinical trial. WES was performed on baseline tumor samples obtained from 18 patients. For seven patients, ctDNA was interrogated using a bespoke hybrid-capture next-generation sequencing (NGS) assay for 48 targeted genes...

The National Heart, Lung, and Blood Institute National MDS Natural History Study (NCT02775383) is a prospective cohort study enrolling cytopenic patients with suspected myelodysplastic syndromes (MDS) to evaluate factors associated with disease. Here, we sequenced 53 genes in bone marrow samples harvested from 1,298 patients diagnosed with myeloid malignancy, including MDS and non-MDS myeloid malignancy, or alternative marrow conditions with cytopenia based on concordance between independent histopathologic reviews (local, centralized, and tertiary to adjudicate disagreements when needed)...

In order to elucidate mechanisms for SARS-CoV-2 vaccination success in hematological neoplasia, we herein provide a comprehensive characterization of the spike-specific T-cell and serological immunity induced in 130 patients in comparison to 91 healthy controls. We studied 121 distinct T-cell subpopulations and the vaccination schemes as putative response predictors. In patients with lymphoid malignancies an insufficient IgG response was accompanied by a normal CD4+ T-cell function. Compared to controls, a spike-specific CD4+ response was detectable in fewer patients with myeloid neoplasia whereas the seroconversion rate was normal...

The European LeukaemiaNet (ELN) measurable residual disease (MRD) working group have published consensus guidelines to standardise molecular genetic MRD testing of the t(8;21)(q22;q22.1) RUNX1::RUNX1T1, inv(16)(p13.1q22) CBFB::MYH11, t(15;17)(q24.1;q21.2) PML::RARA and NPM1 type A markers. A study featuring 29 international laboratories was performed to assess interlaboratory variation of testing, and the subsequent interpretation of results, both crucial to patient safety. The majority of participants in this study were able to detect, accurately quantify and interpret MRD testing results correctly, with a level of proficiency expected from a clinical trial or standard of care setting...

No abstract text is available yet for this article.

Tyrosine kinase inhibitor (TKI) use is critical to the care of patients with chronic myeloid leukemia (CML). Quantitative BCR-ABL1 polymerase chain reaction (qPCR) testing every 3 months during the first year of TKI treatment is recommended to assure achievement of milestone response goals. Real-world evidence for the patterns of qPCR monitoring and TKI adherence in the older patient population is lacking. Using the Surveillance, Epidemiology, and End Results-Medicare database we identified 1192 patients aged >66 years (median age of 74 years) with newly-diagnosed CML followed for ≥13 months from TKI initiation...

American Society of Hematology's Clinical Research Training Institute (CRTI) is a clinical research training program with a competitive application process. Objectives were to compare application scores by applicant and reviewer gender and underrepresented minority (URM) status. We included applications to CRTI from 2003-2019. Application scores were transformed to a 0-100 scale (100 was strongest). Factors considered were applicant and reviewer gender and URM status. We evaluated whether there was an interaction between characteristic and time related to application scores...

Transcription factor Forkhead box P1 (FOXP1) belongs to the same protein family as the FOXOs that are well-known regulators of murine hematopoietic stem progenitor cell (HSPC) maintenance by dampening oxidative stress. FOXP1 and FOXOs can play opposite or similar roles depending on cell context; they can cross-regulate each other's expression. In a previous study, we have shown that FOXP1 contributes to normal human HSP and acute myeloid leukemia (AML) cell growth. Here we investigated the role of FOXP1 in HSPCs and AML cell oxidative stress defense in human context...

Platelets utilize signal transduction pathways facilitated by Class I phosphatidylinositol transfer proteins (PITPs). The two mammalian Class I PITPs, PITPα and PITPβ, are single PITP domain soluble proteins that are encoded by different genes and have 77% sequence identity, though their individual roles in mammalian biology remain uncharacterized. These proteins are believed to shuttle phosphatidylinositol and phosphatidylcholine between separate intracellular membrane compartments, thereby regulating phosphoinositide synthesis and second messenger formation...

Blood cell production is complex, partly genetically determined and influenced by acquired factors. However, there is a paucity of data on how these factors interplay in the context of aging, which is associated with a myeloid proliferation bias, clonal hematopoiesis (CH) and an increased incidence of myeloid cancers. We investigated hereditary and acquired factors underlying blood cell trait variability in a cohort of 2996 related and unrelated women from Quebec aged 55 to 101 years. We performed a genome-wide association study, evaluated the impact of chronic diseases and performed targeted deep sequencing of CH driver genes and X-chromosome inactivation (XCI)-based clonality analyses...

Graduate medical education training in hematology in North America is accredited by the Accreditation Council for Graduate Medical Education (ACGME). Trainees routinely review peripheral blood smears (PBS) in providing clinical care. Competency in PBS review at graduation is required by the ACGME. However, there are no consensus guidelines on best practices surrounding PBS review, education, or competency. We describe the generation of proposed theory and the consensus recommendations developed through a multi-institutional focus group, developed using constructivist grounded theory and a modified nominal group technique...

BACKGROUND: Implementation of international guidelines in Latin American settings requires additional considerations (i.e., values and preferences, resources, accessibility, feasibility, and impact on health equity). OBJECTIVE: To provide evidence-based guidelines about diagnosis of VTE and management in children and during pregnancy. METHODS: We used the GRADE ADOLOPMENT method to adapt recommendations from three American Society of Hematology, ASH, VTE guidelines (Diagnosis of VTE, VTE in Pregnancy and VTE in Pediatric population)...

We report the first population-based period life table, the expected lifetime survival for Medicare and Medicaid beneficiaries with Sickle Cell Disease (SCD), and the disparities in survival by insurance types in the United States. We constructed a retrospective cohort of individuals with diagnosed SCD receiving Common Care (any real-world patterns of care except transplant) based on nationwide Medicare and Medicaid claims data (2008-2016), covering beneficiaries in all 50 states. We analyzed lifetime survival probabilities using Kaplan-Meier curves and projected life expectancies at various ages for all and stratified by sex and insurance types...

Several independent lines of evidence suggest that megakaryocytes are dysfunctional in severe COVID-19. Herein, we characterized peripheral circulating megakaryocytes in a large cohort of COVID-19 inpatients and correlated subpopulation frequencies with clinical outcomes. Using peripheral blood, we show that megakaryocytes are increased in the systemic circulation in COVID-19, and we identify and validate S100A8/A9 as a defining marker of megakaryocyte dysfunction. We further reveal a subpopulation of S100A8/A9+ megakaryocytes that contain SARS-CoV-2 protein and RNA...

Hematopoietic stem cells (HSCs) possess the great self-renewal and multidirectional differentiation ability, which contributes to the continuous generation of various blood cells. Although many intrinsic and extrinsic factors have been found to maintain HSC homeostasis, how to precisely regulate hematopoiesis under stress conditions is poorly understood. In this study, we show that melanocortin receptor 5 (MC5R) is abundantly expressed in hematopoietic stem progenitor cells (HSPCs). Using a MC5R knockout (MC5R-/-) mouse model, we observe that it is not essential for steady-state hematopoiesis...

Multiple myeloma (MM) is a hematological malignancy that emerges from antibody-producing plasma B cells. Proteasome inhibitors, including the FDA-approved bortezomib (BTZ) and carfilzomib (CFZ), are frequently used for the treatment of MM patients. Still, a significant proportion of MM patients are refractory or develop resistance to this class of inhibitors, which represents a significant challenge in the clinic. Thus, identifying factors that determine the potency of proteasome inhibitors in MM is of paramount importance to bolster their efficacy in the clinic...

Cancer enhances the risk of venous thromboembolism, but conversely a hypercoagulant microenvironment also promotes cancer progression. Although anticoagulants have been suggested as potential anticancer treatment, clinical studies on the effect of such modalities on cancer progression have not yet been successful, for unknown reasons. In normal physiology, complex formation between the subundothelial-expressed Tissue Factor (TF) and the blood-borne liver-derived FVII results in induction of the extrinsic coagulation cascade and intracellular signaling via protease activated receptors (PARs)...