Heme

Clinical evidence supports the need of changing the diagnostic criteria of the 2008 updated WHO classification for polycythemia vera (PV), essential thrombocythemia (ET) and primary myelofibrosis (PMF). In JAK2-mutated patients who show characteristic bone marrow (BM) morphology, clinical studies demonstrated that a hemoglobin level of 16.5g/dL in men and 16.0g/dl for women or a hematocrit value of 49% in men and 48% in women are the optimal cut off levels for distinguishing JAK2-mutated ET from "masked/prodromal" PV...

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A patient with refractory multiple myeloma received an infusion of CTL019 cells, a cellular therapy consisting of autologous T cells transduced with an anti-CD19 chimeric antigen receptor, after myeloablative chemotherapy (melphalan, 140 mg per square meter of body-surface area) and autologous stem-cell transplantation. Four years earlier, autologous transplantation with a higher melphalan dose (200 mg per square meter) had induced only a partial, transient response. Autologous transplantation followed by treatment with CTL019 cells led to a complete response with no evidence of progression and no measurable serum or urine monoclonal protein at the most recent evaluation, 12 months after treatment...

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Maintenance of the blood system requires balanced cell fate decisions by hematopoietic stem and progenitor cells (HSPCs). Because cell fate choices are executed at the individual cell level, new single-cell profiling technologies offer exciting possibilities for mapping the dynamic molecular changes underlying HSPC differentiation. Here, we have used single-cell RNA sequencing to profile more than 1600 single HSPCs, and deep sequencing has enabled detection of an average of 6558 protein-coding genes per cell...

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The use of tumor-specific monoclonal antibodies (MAbs) has revolutionize the field of cancer immunotherapy. Although treatment of malignant diseases with MAbs is promising, many patients fail to respond or relapse after an initial response. Both solid tumors and hematological malignancies develop mechanisms that enable them to evade the host immune system by usurping immune checkpoint pathways such as PD-1, PD-2, PDL-1, or PDL-2 (programmed cell death protein-1 or 2 and PD-Ligand 1 or 2), which are expressed on activated T cells and on T-regulatory, B cells, natural killers, monocytes, and dendritic cells...

Multiple myeloma accounts for approximately 10% of hematologic malignancies.The diagnosis requires ≥10% clonal bone marrow plasma cells or a biopsy proven plasmacytoma plus evidence of one or more multiple myeloma defining events (MDE): CRAB (hypercalcemia, renal failure, anemia, or lytic bone lesions) features felt related to the plasma cell disorder, bone marrow clonal plasmacytosis ≥60%, serum involved/uninvolved free light chain (FLC) ratio ≥100 (provided involved FLC is ≥100 mg/L), or >1 focal lesion on magnetic resonance imaging...

Chronic myelomonocytic leukemia (CMML) is a clonal hematopoietic stem cell disorder characterized by overlapping features of myelodysplastic syndromes and myeloproliferative neoplasms. Diagnosis is based on the presence of persistent (>3 months) peripheral blood monocytosis (>1 × 10(9) /L), along with bone marrow dysplasia. Clonal cytogenetic abnormalities occur in ∼20-30% of patients, while >90% have gene mutations. Mutations involving TET2 (∼60%), SRSF2 (∼50%), ASXL1 (∼40%), and RAS (∼30%) are frequent; with only ASXL1 mutations negatively impacting overall survival...

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Mycosis fungoides (MF) is the most common primary cutaneous T-cell lymphoma variant and is closely related to a rare leukemic variant, Sézary syndrome (SS). MF patients at risk of disease progression can now be identified and an international consortium has been established to address the prognostic relevance of specific biologic factors and define a prognostic index. There are a lack of randomized clinical trial data in MF/SS and evidence is based on a traditional "stage-based" approach; treatment of early-stage disease (IA-IIA) involves skin directed therapies which include topical corticosteroids, phototherapy (psoralen with UVA or UVB), topical chemotherapy, topical bexarotene, and radiotherapy including total skin electron beam therapy...

The management of acute promyelocytic leukemia (APL) has considerably evolved during the past two decades. The advent of all-trans retinoic acid (ATRA) and its inclusion in combinatorial regimens with anthracycline chemotherapy has provided cure rates exceeding 80%; however, this widely adopted approach also conveys significant toxicity including severe myelosuppression and rare occurrence of secondary leukemias. More recently, the advent of arsenic trioxide (ATO) and its use in association with ATRA with or without chemotherapy has further improved patient outcome by allowing to minimize the intensity of chemotherapy, thus reducing serious toxicity while maintaining high anti-leukemic efficacy...

In actuality, chronic lymphocytic leukaemia (CLL) remains an incurable haematopoietic malignancy of high prevalence amongst elderly populations in the West. Malignant CLL cells characteristically accumulate in the peripheral blood, bone marrow, lymph nodes, and spleen of CLL patients. There is evidence that CLL cells express Ang2 and Tie1, two central components of the Ang-Tie2 pro-angiogenic pathway. Central to blood vessel development and maintenance, at present it remains unclear how the Ang-Tie2 pathway modulates CLL pathophysiology...

Factor V Leiden (FVLeiden ) is a common hereditary thrombophilia that causes activated protein C (APC) resistance. This review describes many of the most fascinating features of FVLeiden , including background features, mechanisms of hypercoagulability, the founder mutation concept, the "FVLeiden paradox," synergistic interaction with other thrombotic risk factors, the intertwined relationship between FVLeiden and APC resistance testing, and other, uncommon mutations implicated in causing APC resistance. In addition, there are several conditions where laboratory tests for APC resistance and FVLeiden are or can be discrepant, including lupus anticoagulants, anticoagulants such as direct thrombin inhibitors (dabigatran, argatroban, and bivalirudin) and rivaroxaban, as well as pseudohomozygous, pseudo-wildtype, liver transplant, and bone marrow transplant patients...

It is estimated that one-third of the world's population is anemic, the majority being due to iron deficiency (ID). In adults, ID is associated with fatigue in the absence of anemia, restless legs syndrome, pica and, in neonates, delayed growth and development. In adolescents, ID is associated with decrements in learning and behavioral abnormalities. In the absence of a clear cause, search for a source of bleeding is indicated. No single test is diagnostic of ID unless the serum ferritin is low or the percent transferrin saturation is low with an elevated total iron binding capacity...

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No abstract text is available yet for this article.

Anaemia affects roughly a third of the world's population; half the cases are due to iron deficiency. It is a major and global public health problem that affects maternal and child mortality, physical performance, and referral to health-care professionals. Children aged 0-5 years, women of childbearing age, and pregnant women are particularly at risk. Several chronic diseases are frequently associated with iron deficiency anaemia--notably chronic kidney disease, chronic heart failure, cancer, and inflammatory bowel disease...

DISEASE OVERVIEW: The myelodysplastic syndromes (MDS) are a very heterogeneous group of myeloid disorders characterized by peripheral blood cytopenias and increased risk of transformation to acute myelogenous leukemia (AML). MDS occurs more frequently in older males and in individuals with prior exposure to cytotoxic therapy. DIAGNOSIS: Diagnosis of MDS is based on morphological evidence of dysplasia upon visual examination of a bone marrow aspirate and biopsy. Information obtained from additional studies such as karyotype, flow cytometry, or molecular genetics is complementary but not diagnostic...