Vera Ghali, MD

Sézary Syndrome is a rare and aggressive ́leukemic variant of Cutaneous T-Cell Lymphoma (CTCL), a group of mature T-cell malignancies primarily affecting skin of which mycosis fungoides (MF) is the most common subtype. Sézary Syndrome involves the skin, blood, and lymph nodes and accounts for 4% of of all CTCL cases. It is associated with impaired immune surveillance in peripheral blood and skin which may predispose patients to the development of secondary malignancies. Also, patients with Sézary Syndrome are frequently treated with immunosuppressive agents that further predispose to an increased risk of cancer. It is distinguished from other skin lymphomas by the presence of Sézary cancerous cells circulating in peripheral blood. Sézary cells are pleomorphic T-cells with the characteristic cerebriform, brain-shaped, convoluted nuclei that are seen on a peripheral blood smear (PBS) and have pathological quantities of mucopolysaccharides. Sézary Syndrome is considered a late-stage of mycosis fungoides with lymphadenopathy. It is further distinguished by epidermotropism, lymphocytes residing in the epidermis and neoplastic CD4+ lymphocytes with the formation of Pautrier's microabscesses, which are hallmarks of Sézary Syndrome. Sézary Syndrome has symptoms which mimic severe inflamnatory skin diseases with erythroderma and pruritus, ectropion, palmo-plantar keratoderma, alopecia, and hepatosplenomegaly. Diagnosis is by tumor, node, metastasis, and blood (TNMB) analyses: skin biopsies for T-cell infiltrates; flow cytometry to identify Sézary cells and to determine tumor burden of >1000/microL or a high CD4/CD8 ratio; molecular studies of T-cell receptor gene (TCR) sequencing to confirm a single clonal expansion of malignant cells. Sézary Syndrome is managed with topical corticosteroids, localized phototherapy, total skin electron beam therapy (TSEBT) and psoralen, and extracorporeal photopheresis (ECP). Systemic therapies include interferon-alpha; monoclonal antibodies such as mogamulizumab, brentuximab vedotin, or alemtuzumab; oral retinoids such as bexarotene or histone deacetylase (HDAC) inhibitors such as vorinostat and romidepsin. For some eligible and fit patients, allogenic hematopoietic stem cell transplantation (allo-HSCT) may be curative. The present study demonstrated that patients with Sézary Syndrome had 6 times higher cancer risk with 2 times higher risk of all solid cancers, and 50 times higher risk of all hematologic cancers. The highest risk was observed for follicular lymphoma (FL). Also, patients had significantly increased risk for melanoma, squamous cell carcinoma (SCC), and basal cell carcinoma (BCC). The results of the study underscore regular monitoring of all patients with Sézary Syndrome for possible signs of other cancers during all clinical visits for the early detection of subsequent malignancies.

Wishing you my friends a happy day ✨️ "Dance of Autumn Leaves" Suzuki Harunobu Masterpieces of Japan

The American Society of Hematology (ASH) 2026 guidelines for the management of Primary Immune Thrombocytopenia (ITP) in adults. Novel recommendations include: 1-Initial therapy with a combination of rituximab plus corticosteroids, or a thrombopoietic agent plus corticosteroids rather than corticosteroids alone (conditional recommendation). 2-A thrombopoietic agent (strong recommendation) or rituximab (conditional recommendation) for patients who failed first-line therapy with corticosteroids. ITP is an autoimmune disorder that occurs when the immune system targets and destroys the body's own platelets as defined by thrombocytopenia of <100×10×9/L, and characterized by autoimmune-mediated platelet destruction and impaired platelet production. It may occur in isolation (Primary ITP), or in association with predisposing conditions triggered by infections like HIV, hepatitis, H. pylori, or caused by autoimmune disorders such as SLE (Secondary ITP) with incidence that peaks in early childhood or older adulthood. It is characterized by symptoms of bleeding, petechiae, purpura, epistaxis, menorrhagia, hematuria, fatigue, and intracranial hemorrhage (ICH). Traditionally, ITP is treated with corticosteroids and IVIG as first-line therapy, and thrombopoietin receptor agonists (TPO-RAs) such as eltrombopag and romiplostim which stimilate bone marrow megakaryocytes to increase platelet production; rituximab, a second-line monoclonal antibody that targets and depletes B-cell surface antigen CD20+ that produces anti-platelet autoantibodies when first-line therapy has failed.

"The Selfish Gene" by Richard Dawkins, was published in October 1976, fifty years ago, a highly influential book focusing on a gene-centric view as a driver of evolutionary processes. However, after decades of progress in evolutionary development, biological research, genomics, and epigenetics, it has become evident that a gene-centric model is an oversimplification and a reductionist view. Phenotypes and traits are heavily shaped by how organisms interact with their environment. A DNA cannot replicate itself in isolation as it requires other cellular enzymes and proteins to proofread, repair, and copy genetic material. Organisms actively shape their own evolution through behavioral plasticity and learning and change their environments accordingly, thus modifying the natural selection processes by acting on them. Biological complexity arises from interdependent genetic networks and interactions among multiple genes. "Selfish" as a title is a misnomer and misleading. The book is not about individual genes acting with intent or causing "selfish" behavior. The book discusses altruistic behavior and why organisms exhibit self-sacrificing or cooperative behavior toward their offspring and relatives because they share copies of their genes which helps identical copies of their genes to survive. Dawkins in retrospect, regretted naming his book "The Selfish Gene", as "The Immortal Gene" better captured the idea of genes persisting across generations, as proposed by his publisher. Interestingly, Dawkins coined the term "meme" as a unit of cultural transmission that replicates, mutates, and survives by spreading from mind to mind under a form of selection parallel to biological evolution. Inspite of Richard Dawkins fascinating ideas, it is important to note that a gene-centric model of evolution is nowadays imperfect. A model that focuses on the complexity of genetic evolution and its multi-faceted interactions and inherent complex mechanisms better reflects the life cycle and its evolutionary continuum.

A study in Uganda demonstrated that hydroxyurea conferred sustained neurocognitive benefits on children with Sickle Cell Anemia (SCA). The study was conducted on children 3-9 years in a 2.5 year, single-arm, open label trial. The results showed that hydroxyurea conferred multiple neurological benefits with improved cognition, attention, memory, concentration, analytic function, and planning. Neurological and cognitive improvements are caused by hydroxyurea's benefits which raises Hb and fetal Hb (HBF) which have a positive impact on improved general well-being and reduction in acute SCA complications, fewer blood transfusions, reduced risk of strokes, and sickle cell cerebrovascular injury. Effects of hydroxyurea on severity of cerebrovascular injury were measured by parameters such as neurocognitive functioning, incident of strokes, and abnormal transcranial Doppler (TCD) cerebral arterial flow velocity. Hydroxyurea in SCD works by enhancing oxygen delivery to the brain and vital organs, reducing vascular stress, and preventing or slowing brain injury. It stimulates the production of HbF and raises overall Hb levels, thus improving chronic hemolytic anemia and increases blood's oxygen-carrying capacity. It lowers risks of strokes and decreases the risk or progression of silent cerebral infarcts and overt strokes which are drivers of cognitive decline in SCD. It also suppreses cell-stress signaling and inflammation, decreases general severity of Vaso Occlusive Crises (VOC) in SCD which occur when sickled RBCs block capillaries cutting off oxygen supply and resulting in severe pain in chest, extremities, joints and bones, and reduces incidence of Acute Chest Syndrome, a complication of SCD and VOC. SCD is exacerbated by the higher burden of risk factors such as infections and poor socioeconomic status (SES). The results of the study underscore the importance of early initiation of hydroxyurea and increasing its access to all children with SCA in Sub Saharan Africa and other regions in the world with a high incidence of SCD.

"Wishing you my friends a good day ✨️ "Gaze of Silence" Paul Klee

In phase 3 of the DELLphi-305 Trial involving patients with Extensive-Stage Small Cell Lung Cancer (ES-SCLC), the median OS was 21.1 months when tarlatamab, a bispecific T-cell engager targeting delta-like ligand 3 (DLL3) and CD 3 was added to durvalumab, an anti-programed death ligand 1 agent, when administered as combination maintenance therapy vs 12.7 months with durvalumab alone with better progression-free survival. This significant improvement was achieved with the use of a combination of both immunotherapeutic agents after initial chemo-immunotherapy and after first remission when it is unclear. Adverse events (AEs) of grade 3 or higher occurred in 46.8% of patients receiving combination therapy and 40.6% in those who received durvalumab alone. Cytokine release syndrome (CRS) of grade 1 or 2 was seen in nearly half the patients receiving the combination therapy. ES-SCLC is a highly aggressive and rapidly progressing type of adenocarcinoma with poor prognosis. It occurs when cancer has spread beyond the lung where it started and metastasized to the contralateral lung, distant lymph nodes, and other organs like the brain, liver, and bones. It is driven by cumulative lifetime genetic mutations caused by smoking and environmental toxins that lead to the universal inactivation of key tumor-suppression genes specifically TP53 and RB 1. The new combination treatment under study holds the promise for longer overall survival for patients with ES-SCLC.

The importance of hepcidin assays in the diagnosis of iron disorders. Systemic iron homeostasis is predominantly controlled by hepcidin which is secreted by hepatocytes. Hepcidin is a peptide hormone, the central hormonal regulator of systemic iron homeostasis and a critical mediator and biomarker of iron disorders. It has a central role in controlling dietary iron absorption, iron recycling by macrophages, and iron storage through its interaction with the iron exporter ferroportin, a ferrous iron transporter that exports iron out of cells into the blood stream. Its synthesis is regulated by iron status, inflammation, and erythropoietic demand via hepatic bone morphogenetic protein-SMAD pathway and its modulators such as erythroferrone and IL-6-janus kinase-signal transducer and activator of transcription signaling. Hepcidin also acts as an acute-phase reactant during infections and inflammation. Genetic hepcidin deficiency causes hemochromatosis and predisposes to infections, whereas its excess causes iron-refractory-iron deficiency anemia (IRIDA). Hepcidin assays can be used to determine iron overload disorders, iron-loading anemia, transfusional iron overload, inherited IRIDA, inflammation, and erythroid activity. However, correct interpretation of hepcidin assays requires distinguishing hepcidin's role as a pathogenic driver vs a biomarker of disease. Currently, hepcidin assays are most helpful in complex or rare iron disorders where existing approaches are not sufficient for decision making strategies.

Despite advances in understanding Burkitt Lymphoma (BL), global survival gaps still exist. Novel insights into biomarkers have emerged with novel genomic analysis and new treaments such as targeted therapies with reduced toxicities have led to tailored therapies. However, survival disparities still persist especially in resource-limited settings where globally, most BL patients live, and among patients with relapsed/refractory Burkitt Lymphoma (R/R BL). BL is a rapidly-growing aggressive B-cell lymphoma classified into endemic, sporadic, or immunodeficiency-associated BL based on epidemiological features. Recent genomic and epidemiological studies distinguish Epstein-Barr virus (EBV)-positive and EBV-negative BL. In high-income countries (HICs), BL is 95% curable with early detection, intensive multi-agent chemotherapy, and antibody-based therapy. In contrast, survival in Sub-Saharan Africa (SSA), survival rarely exceeds 50%, reflecting diagnostic delays, high rates of treatment abandonment, and limited access to chemotherapy. Approximately 95% of EBV-positive BL predominate in pediatric SSA patients; in North Africa and Latin America, EBV is detectable in 40%-70% of cases. In Asia, reported EBV positivity varies between 20%-80%. Among individuals with HIV infection, 40%-70% of BL-positive patients are EBV positive. There is a strong correlation between P. falciparum, EBV infection, and BL. underlying the fact that some immune mechanisms at high risk to tolerate repeated malaria exposure and severe infections. Immune mechanisms in primary infection with EBV seem to confer protection against severe P. falciparum while increasing long-term BL risk among survivors, with some parasitic strains more oncogenic than others. The paradoxical interplay between infection with P. falciparum and BL suggests that BL develops in children who are otherwise resistant to severe malaria, with BL risk becomes significant only after a high number of repeated infections (>50) and continues to increase with additional exposure in malaria-resistant children which shows that P. falciparum is a critical driver of BL pathogenesis by modulating EBV. Althogh EBV persists silently in memory B-cells (latency 0), malaria-driven antigenic stimulation causes these cells to remember the germinal cells (GCs) thus reactivating EBV growth program (latency III) resulting in full protein expression, virion production, and shedding. Moreover, P. falciparum directly stimulates the proliferation of infected B-cells while at the same time, suppressing T-cell responses that normally control EBV. These processes significantly increase EBV viral load and shedding, explaining why children with BL have 5 to 13 times higher antibody titer against both pathogens than healthy persons. The pathogen interaction represents an evolutionary trade-off in which co-infection confers survival advantage to children and enhanced transmission of both pathogens. Early EBV infection in the first year of life provides a survival advantage against malaria-associated mortality in regions where malaria is endemic. EBV derived BH RF1/vIL-10 modulates host immune responses dampening excessive inflammation associated with severe malaria and reducing mortality, an effective immunomodulation that benefits both the host and P. falciparum pathogen. Germline susceptibilty to BL has been observed in rare inborn errors of immunity (IEI) including X-linked lympho-proliferative disease, X-MEN syndrome, ataxia telangiectasia, and Williams-Beuren syndromes. Germline variants that reduce malaria risk, such as sickle-cell trait and variants at ABO locus, are associated with decreased BL risk. The present analytical study underscores the importance of understanding the pathogenesis of BL, accurate diagnosis, the underlying genomics, and providing more accessible treatments in resource-limited regions in order to close the survival gaps in BL as BL is a highly curable disease with early detection.

Wishing you my friends a happy day ✨️ "The Soup" Pablo Picasso