Hematodiagnóstica

10/04/2019

Management of mycosis fungoides-type cutaneous T-cell lymphoma (MF-CTCL): focus on chlormethine gel

Mycosis fungoides (MF) is a low-grade cutaneous lymphoma accounting for more than half of primary cutaneous T-cell lymphomas (CTCLs). Due to the rarity of CTCL, randomized studies are lacking, and treatment is based mainly on the recent published European Organisation for Research and Treatment of Cancer guidelines. Basically, early-stage MF is treated with skin-directed treatments, whereas advanced-stage MF requires more aggressive therapies. Among the skin-directed therapies, nitrogen mustard has been used for more than 50 years. A gel formulation was developed recently, showing a slight decrease in efficacy, counterbalanced by better tolerance (essentially due to a decrease in delayed hypersensitivity reactions).
Read more: https://www.dovepress.com/management-of-mycosis-fungoides-type-cutaneous-t-cell-lymphoma-mf-ctcl-peer-reviewed-fulltext-article-CMAR

08/04/2019

Benralizumab for PDGFRA-Negative Hypereosinophilic Syndrome

Hypereosinophilic syndrome is a group of rare chronic disorders that are defined by an absolute eosinophil count (i.e., the number of eosinophils in blood) of at least 1500 cells per cubic millimeter and evidence of eosinophil-related clinical manifestations that can include intractable pruritus, pulmonary infiltrates, eosinophilic gastroenteritis, endomyocardial fibrosis, and thromboembolism. The goal of treatment is a reduction in blood and tissue eosinophilia, thereby preventing further organ damage. Conventional therapies, including glucocorticoids and immunomodulatory and cytotoxic therapies, have variable efficacy and substantial toxic effects. Despite promising early trial results with antibodies against interleukin-5, the only therapy for this disorder that has been approved by the Food and Drug Administration (FDA) is imatinib mesylate, a tyrosine kinase inhibitor that is effective in the treatment of primary myeloid forms of the disease, including myeloid neoplasms associated with the gene encoding platelet-derived growth factor receptor alpha (PDGFRA); new therapies that can help establish disease control in PDGFRA-negative hypereosinophilic syndrome are needed.
Read more: https://www.nejm.org/doi/full/10.1056/NEJMoa1812185?query=featured_home

16/11/2018

Wow

Acquired α-thalassemia associated with myelodysplastic syndromes

An 83-year old white man with microcytic anemia (hemoglobin 119 g/L; mean corpuscular volume 69 fL) and thrombocytopenia (120 × 109/L) had prominent red cell changes (microcytosis, target cells, elliptocytes, schistocytes) (panel A; original magnification ×40, Wright Giemsa stain), and ∼80% neutrophils were hypogranular and/or abnormally segmented (panel B; original magnification ×40, Wright Giemsa stain) on blood film. Hemoglobin electrophoresis and high-performance liquid chromatography were normal. Approximately 5% red cells showed hemoglobin H (HbH) inclusion bodies (panel C; original magnification ×100, brilliant cresyl blue stain). The i+LABORATORY α-thalassemia immunochromatographic strip test was positive (panel D), consistent with α-thalassemia. The patient lacked family history of thalassemia, had previous normal presentation (no jaundice/splenomegaly), normal red blood cell parameters, and granulocyte morphology. This led to clinical suspicion of acquired HbH disease associated with myelodysplastic syndromes (MDS). Bone marrow showed trilineage dysplasia–multinucleated erythroids (panel E; original magnification ×40, Wright Giemsa stain), hypolobate megakaryocytes (panel F, ×40), and hypogranular granulocytes (panel G, ×40). Ringed sideroblasts (23%) were noted (panels H-I; original magnification ×100, potassium hexacyanoferrate with neutral red counterstain). MDS with ringed sideroblasts and multilineage dysplasia was diagnosed. Cytogenetic analysis showed +14. α-Thalassemia is an autosomal recessive inherited disorder of red blood cells. It can also occur as an acquired defect in disorders associated with ineffective erythropoiesis, especially MDS. Acquired α-thalassemia is due to acquired somatic mutations in the ATRX gene (Xq21.1), resulting in downregulation of α-globin gene expression.

http://www.bloodjournal.org/content/132/20/2209

09/11/2018

😉

B & B: basophils and bleeding, an atypical case of acute promyelocytic leukemia

A 59-year-old woman was hospitalized for investigation of spontaneous bruises on arms and legs and asthenia. Complete blood count and blood smear review showed pancytopenia (platelets 78 × 109/L, hemoglobin concentration 10.6 g/dL, leukocytes 1.8 × 109/L) with 10% blast cells and 13% basophils (0.2 × 109/L). Coagulation tests, including fibrinogen and D-dimers, were normal. Bone marrow examination showed 64% hypergranular blasts with Auer rods (panels A and B, black arrows; original magnification ×100, May-Grünwald Giemsa stain), typical of acute promyelocytic leukemia (APL) and 13% basophils with abnormal features: hypergranularity and abnormal granular repartition (red arrows). Flow cytometry (panel C) confirmed a typical profile of promyelocytic cells (cMPO+, CD34−, HLA DR−, CD117+, CD33+, CD13+, CD123−) and basophils (CD11b+, CD25+, CD123+, CD13+, CD33+, CD44+) with an abnormal immunophenotypic profile (CD38−, CD117low). Cytogenetic analysis (panel D) revealed t(15;17)(q24;q21), and molecular analysis showed classical PML-RARA transcript. Classical APL treatment was given. Basophilia increased to 0.39 ×109/L at day 19 and normalized by day 24. The patient has started her first consolidation without problems. Basophilia at diagnosis of APL is very uncommon. This case highlights that basophilia can be associated with an APL clone. Basophilia at presentation of APL has been reported and said to have an increased risk of bleeding, not seen in this patient.
http://www.bloodjournal.org/content/132/19/2107

08/11/2018

Inhibition of Casein Kinase 1 Alpha in Acute Myeloid Leukemia

Acute myeloid leukemia (AML) is a genetically heterogeneous cancer that arises in hematopoietic stem cells. For the past 40 years, standard treatment for AML has consisted of a combination of two chemotherapeutic agents, cytarabine and an anthracycline. This regimen results in high rates of remission but, in the majority of cases, fails to eradicate the residual leukemic stem cells that are the reason for relapse and poor outcomes in patients with AML. The comprehensive genetic analysis of AML in the past 10 years has revealed recurrent, somatically mutated genes, leading to the development of new targeted therapies including inhibitors of fms-like tyrosine kinase 3 (FLT3) and isocitrate dehydrogenase 1 and 2. However, monotherapy with these drugs does not result in durable responses, and combination with chemotherapy has only modestly improved outcomes; thus, new drug targets in patients with AML are needed.
Read more: https://www.nejm.org/doi/full/10.1056/NEJMcibr1811318?query=featured_home

16/10/2018

😍

Novel Immunotherapies for T Cell Lymphoma and Leukemia

In the last few years, immunotherapy has revolutionized the treatment of cancer. After the first wave of clinical responses with monoclonal antibodies, a new generation of immunotherapies has become available. Checkpoint inhibitors, bispecific antibodies, and chimeric antigen receptor T cells (CART) have led to unprecedented responses in patients with relapsed and refractory neoplasms. After being validated in the most common cancer subtypes, some of these approaches are now being tested in rare neoplasms such as T cell lymphoma (TCL) and leukemia (T-ALL). The need for effective and safe new therapies is urgent, as the overall prognosis for these rare diseases is generally poor.
Read more: https://link.springer.com/article/10.1007%2Fs11899-018-0480-8

05/10/2018

🤓

An unexpected association of hematologic malignancies

An 83-year-old man presented with hematuria and bone pain. Computed tomography–scan imaging demonstrated multiple osteolytic lesions and vertebral collapse. A complete blood count showed anemia with hemoglobin of 9.1 g/dL and normal white blood count and platelets, 4.95 × 109/L and 198 × 109/L, respectively. Total protein was at 105 g/L, with electrophoresis revealing a monoclonal band, identified as immunoglobulin G ĸ at 50 g/L. Bone marrow smear examination found plasma cells comprising 38% of total nucleated cells (TNCs) and an unexpected infiltration (3%) of abnormal mast cells (MCs) with a spindle-shaped morphology (panels A-B; May-Grünwald Giemsa staining, original magnification ×1000). Serum tryptase was elevated at 161 µg/L, and next-generation sequencing revealed D816Y mutation at the exon 17 of the kit gene, found in the MCs, confirming a diagnosis of systemic mastocytosis with an associated hematological neoplasm (SM-AHN). Flow cytometry analysis showed aberrant expression of CD2 and CD25 on the MCs. After 3 months of lenalidomide and dexamethasone, bone marrow plasma cells were at 2% of TNCs, but the infiltrate of abnormal MCs remained unchanged, and serum tryptase was still elevated at 182 µg/L. This case of SM-AHN involving D816Y mutation and myeloma demonstrates the benefit of microscopic examination as relatively common diseases can hide even the rarest hematologic malignancies.
http://www.bloodjournal.org/content/132/14/1545

26/09/2018

Linfocitos T maduros 😘

Muchos informes históricos de la mononucleosis infecciosa (MI) dan crédito ya sea a Filatow (1885), un pediatra de origen ruso o Emil Pfeiffer (1889) con la descripción inicial de las manifestaciones clínicas de la enfermedad. .
Empero, la entidad clínica de la MI aún no había sido definida, por lo que varios de los casos fueron diagnosticados erróneamente como leucemia aguda (LA)con cura aparente (Jackson y Smith 1915). Turk (1907) y Osler (1915) encontraron casos en los que se reconoció la aparición ocasional de una linfocitosis con una aparente infección. Cabot (1913) advirtió en contra de hacer el diagnóstico de leucemia aguda en este entorno. También señaló que los linfocitos asociados con infección podrían ser distinguidos de los que se observan en la LA, en aspectos morfológicos.

Se produjo un gran avance con el informe de Sprunt & Evans (1920) de seis pacientes del Hospital Johns Hopkins. Tres de los pacientes eran estudiantes de medicina; los otros 3 adultos jóvenes - una leucocitosis mononuclear fue documentada en todos los casos. La morfología celular de las leucocitosis era diferentes a las células de leucemia aguda. Además, señalaron la ausencia de anemia o tendencias hemorrágicas y el excelente pronóstico de la enfermedad en comparación con una leucemia. Aunque el término "mononucleosis infecciosa" había sido utilizado previamente por Baetjer & Ruhrah en 1915, este informe debe ser acreditado como el que proporciona el término y su significado actual. Porque de la prominencia de la faringitis, se sugirió que el tracto respiratorio sirvió como sitio inicial de la enfermedad.

18/07/2018

Excelente artículo...

Understanding how monocyte cells generate specialized immune system cells may help target immunity against cancer

14/07/2018

Love Chemistry...😎