Caplacizumab as an add-on therapy in a 7-year-old girl with exacerbated immune-mediated thrombotic thrombocytopenic purpura, a case report and literature review.

The cornerstone treatment for immune-mediated thrombotic thrombocytopenic purpura (iTTP) in children is a combination of therapeutic plasma exchange (TPE), corticosteroids, and rituximab. Caplacizumab is an anti-von Willebrand factor (VWF) NANOBODY molecule approved as a frontline therapy of iTTP for adults and children aged ≥12 years. Using caplacizumab in children aged <12 years remains a gray area based on recommendations but with no marketing authorization. We report the first case of a pediatric patient with iTTP successfully treated with a caplacizumab dose adjustment of 5 mg daily based on ADAMTS13 activity. We also review all published cases of iTTP in children aged <12 years treated with caplacizumab. This is a 7-year-old girl with clinical thrombotic microangiopathy, in the absence of diarrhea and kidney injury. With a French score of 2 and a PLASMIC score of 7 (high risk), the diagnosis of TTP was suspected and later confirmed by severely low ADAMTS13 activity (<5%). Immune-mediated TTP was distinguished from the congenital one due to the presence of a functional ADAMTS13 inhibitor. Daily TPE and intravenous corticosteroids were started on day 0 (D0). Rituximab was added on D4, and due to refractoriness under daily TPE, we considered off-label administration of caplacizumab from D12. A clinical answer, with a significant increase in the platelet count, was observed within 48 h. A complete ADAMTS13 recovery was reached on D62. No major adverse events were observed during the treatment. She was discharged from the hospital over 3 months ago with a platelet count still within normal ranges. In the literature, we identified a total of four case reports describing five iTTP patients aged <12 years treated with caplacizumab, with a 100% success and tolerability rate. These published data attest to the efficacy and safety of the systematic use of caplacizumab and rituximab as frontline therapy in pediatric iTTP under 12 years of age. Therefore, prospective data are needed to support commercial authorization of caplacizumab in this subpopulation. Close monitoring of ADAMTS13 activity is particularly of interest among children to limit the number of caplacizumab injections.

Serum visfatin level in ß-thalassemia and its correlation with disease severity.

Thalassemia is a group of genetic hematological conditions characterized by the defective synthesis of one or more hemoglobin chains. This genetic anomaly alters globin chain balance, causing hemolysis, ineffective erythropoiesis, and chronic inflammatory diseases. The proinflammatory adipocytokine visfatin is predominantly produced in visceral adipose tissue. Its evaluation in individuals with thalassemia may provide valuable insights into the assessment of disease severity. The aim of this study was to investigate the potential role of visfatin in the development of ß-thalassemia and its association with the severity of the illness. The study included 40 patients with ß-thalassemia and ten healthy individuals matched by age and sex. Serum visfatin level was measured using ELISA. We found that individuals with ß-thalassemia major had significantly higher levels of serum visfatin than those with ß-thalassemia minor and the control group (P < 0.001). A receiver operating characteristic curve revealed that serum visfatin levels were different in the three groups. Our results suggest that the serum level of visfatin is significantly correlated with the severity of ß-thalassemia.

HLA alleles, haplotypes frequencies, and their association with hematological disorders: a report from 1550 families whose patients underwent allogeneic bone marrow transplantation in Egypt.

HLA alleles are representative of ethnicities and may play important roles in predisposition to hematological disorders. We analyzed DNA samples for HLA-A, -B, -C, -DRB1, and -DQB1 loci, from 1550 patients and 4450 potential related donors by PCR-SSO (Polymerase chain reaction sequence-specific oligonucleotides) and estimated allele frequencies in donors and patients from 1550 families who underwent bone marrow transplantation (BMT) in Egypt. We also studied the association between HLA allele frequencies and incidence of acute myeloid leukemia, acute lymphoblastic leukemia, and severe aplastic anemia. The most frequently observed HLA class I alleles were HLA- A*01:01 (16.9%), A*02:01 (16.1%), B*41:01 (8.7%), B*49:01 (7.3%), C*06:02 (25.1%), and C*07:01 (25.1%), and the most frequently observed class II alleles were HLA-DRB1*11:01 (11.8%), DRB1*03:01 (11.6%), DQB1*03:01 (27.5%), and DQB1*05:01 (18.9%). The most frequently observed haplotypes were A*33:01~B*14:02 ~ DRB1*01:02 (2.35%) and A*01:01~B*52:01~DRB1*15:01 (2.11%). HLA-DRB1*07:01 was associated with higher AML odds (OR, 1.26; 95% CI, 1.02-1.55; p = 0.030). Only HLA-B38 antigen showed a trend towards increased odds of ALL (OR, 1.52; 95% CI, 1.00-2.30; p = 0.049) HLA-A*02:01, -B*14:02, and -DRB1*15:01 were associated with higher odds of SAA (A*02:01: OR, 1.35; 95% CI, 1.07-1.70; p = 0.010; B*14:02: OR, 1.43; 95% CI, 1.06-1.93; p = 0.020; DRB1*15:01: OR, 1.32; 95% CI, 1.07-1.64; p = 0.011). This study provides estimates of HLA allele and haplotype frequencies and their association with hematological disorders in an Egyptian population.

Fat Embolism Due to Avascular Necrosis Leading to Acute Chest Syndrome in Sickle Cell Disease in a Youth: A Lethal Encounter.

Fat embolism syndrome (FES) is a rather uncommon presentation in sickle cell disease (SCD), most frequently happening in the context of long bone fractures following trauma. On the other hand, nontraumatic scenarios and nonorthopedic injuries have been documented to cause fat embolisms. This article describes the case of an 18-year-old male patient who had a known case of SCD (SS pattern). The patient complained of hip pain, and it was discovered that he had avascular necrosis of the right femoral head. The patient was started on opioid analgesics and started to respond to treatment; however, on the third day of admission, his condition deteriorated, oxygen saturation dropped, and the patient was shifted to the intensive care unit, where he was diagnosed with FES due to avascular necrosis. The patient's condition further deteriorated; he could not be saved and succumbed to death within one day. Very rarely has SCD with FES been reported in the literature.

MicroRNA target homeobox messenger RNA in HIV induced hematopoietic inhibition.

Cytopenias are a common occurrence due to abnormal hematopoiesis persistent in patients suffering from and advancing with HIV/AIDS. In order to develop efficacious therapies against cytopenias, it is necessary to understand the mechanisms by which HIV infection affects the differentiation of hematopoietic stem-progenitor cells (HSPCs), causing hematopoietic inhibition, that leads to hematological disorders. Currently, only the antiretrovirals that are being used to treat HIV infection and indirectly lower the levels of virus replication also co-attenuate cytopenias. The evidence available suggests that this indirect efficacy may not prevail for the lifetime of the infected patients, and the acquired immunodeficiency can overtake the beneficial consequences of decreased virus replication. As cited in this article, we and our colleagues are the first to make a foray into the involvement of microRNAs and their use as potential interventional treatments for the cytopenias that occur with HIV/AIDS. Herein, we progressed further in the direction of the mechanisms of the involvement of homeobox gene regulation to cause cytopenias. We had previously shown that HIV-1 inhibits multi-lineage hematopoiesis of the CD34+ cells using SCID-hu Thy/Liv animals in vivo. Furthermore, we demonstrated that the virus-induced hematopoietic inhibition occurred despite the CD34+ cells being resistant to HIV-1 infection. We set out to search for the specific host factors secreted by CD4+ T-cells that likely participate in the inhibition of hematopoiesis of the HIV infection-resistant CD34+ cells. More recently, we reported the identification of virus-infected CD4+ thymocyte-secreted miRNA-15a and miRNA-24 and that their differential expression following HIV infection causes the indirect inhibition of hematopoiesis. We then hypothesized that the observed miRNA differential expression in the virus-infected T-cells causes the abnormal regulation of homeobox (HOX) gene-encoded transcriptomes in the CD34+ cells, affecting specific MAPK signaling and CD34+ cell fate, thereby disrupting normal hematopoiesis. We present that in HIV infection, miRNA-mediated post-transcriptional dysregulation of HOXB3 mRNA inhibits multi-lineage hematopoiesis, which translates into hematological disorders in virus-infected patients with HIV/AIDS. These observations portend specific microRNA candidates for potential efficacy against the virus-induced cytopenias that are otherwise not treatable by the existing HAART/ART regimens, which are primarily designed and applicable for the attenuation of virus replication.

Concurrent Challenges in Idiopathic Hypereosinophilic Syndrome Complicating Beta-Thalassemia Major: A Case Report.

This case report highlights the uncommon idiopathic hypereosinophilic syndrome (HES) complicating beta-thalassemia major, presenting a diagnostic and management challenge. Beta-thalassemia major, characterized by impaired beta-globin synthesis, necessitates regular blood transfusions and iron chelation therapy. HES, a rare disorder marked by persistent eosinophilia, adds complexity to the clinical course. We present the case of a 27-year-old male with beta-thalassemia major who developed fever, weakness, and weight loss and was subsequently diagnosed with HES. Treatment involved antibiotics, blood transfusions, and corticosteroids, leading to clinical improvement. This case underscores the need to further understand the relationship between thalassemia and eosinophilia and the importance of comprehensive evaluation in patients with overlapping hematological disorders.

Angina Bullosa Hemorrhagica - A Case Series.

Angina bullosa hemorrhagica (ABH) is an oral subepithelial blood blister with poorly understood etiopathogenesis, which is not attributable to blood dyscrasias or vesiculobullous disorders. These hemorrhagic bullae spontaneously rupture within minutes to hours, resulting in ragged, often painless, superficial erosions that heal spontaneously within 1 week without scarring. The lesions are usually solitary, and sometimes cause extreme anxiety in patients. Treatment is generally symptomatic. We report a series of four such patients. No treatment was given, except for reassurance and anxiolytics.

In Silico Evaluation of Coding and Non-Coding nsSNPs in the Thrombopoietin Receptor (MPL) Proto-Oncogene: Assessing Their Influence on Protein Stability, Structure, and Function.

The thrombopoietin receptor (MPL) gene is a critical regulator of hematopoiesis, and any alterations in its structure or function can result in a range of hematological disorders. Non-synonymous single nucleotide polymorphisms (nsSNPs) in MPL have the potential to disrupt normal protein function, prompting our investigation into the most deleterious MPL SNPs and the associated structural changes affecting protein-protein interactions. We employed a comprehensive suite of bioinformatics tools, including PredictSNP, InterPro, ConSurf, I-Mutant2.0, MUpro, Musitedeep, Project HOPE, STRING, RegulomeDB, Mutpred2, CScape, and CScape Somatic, to analyze 635 nsSNPs within the MPL gene. Among the analyzed nsSNPs, PredictSNP identified 28 as significantly pathogenic, revealing three critical functional domains within MPL. Ten of these nsSNPs exhibited high conservation scores, indicating potential effects on protein structure and function, while 14 were found to compromise MPL protein stability. Although the most harmful nsSNPs did not directly impact post-translational modification sites, 13 had the capacity to substantially alter the protein's physicochemical properties. Some mutations posed a risk to vital protein-protein interactions crucial for hematological functions, and three non-coding region nsSNPs displayed significant regulatory potential with potential implications for hematopoiesis. Furthermore, 13 out of 21 nsSNPs evaluated were classified as high-risk pathogenic variants by Mutpred2. Notably, amino acid alterations such as C291S, T293N, D295G, and W435C, while impactful on protein stability and function, were deemed non-oncogenic "passenger" mutations. Our study underscores the substantial impact of missense nsSNPs on MPL protein structure and function. Given MPL's central role in hematopoiesis, these mutations can significantly disrupt hematological processes, potentially leading to a variety of disorders. The identified high-risk pathogenic nsSNPs may hold promise as potential biomarkers or therapeutic targets for hematological diseases. This research lays the foundation for future investigations into the MPL gene's role in the realm of hematological health and diseases.

Porto-spleno-mesenteric venous thrombosis after elective splenectomy: a retrospective cohort study.

Background: Elective splenectomy is the main treatment for a wide range of haematological diseases. Porto-spleno-mesenteric venous thrombosis represents one of the most severe complications of this procedure. The aim of this study was to evaluate risk factors associated with development of porto-spleno-mesenteric venous thrombosis after elective splenectomy. Methods: All cases of elective splenectomy carried out from April 1st 2017 to January 31st 2023 were included in this single centre retrospective cohort study. Patients' demographics and perioperative data were analysed and correlated with the incidence of postoperative thrombosis. All patients underwent postoperative doppler ultrasound screening for thrombosis. Analysis was performed using SPSS 28, with p-value < 0.05 considered significant. Results: Twenty-two patients (10 women, 12 men) underwent splenectomy during the study period. Indications were: immune thrombocytopenia (n: 6), myeloproliferative disorder (n: 6), hereditary spherocytosis (n: 4), thalassemia (n: 1), lymphoma (n: 1), leukaemia (n: 1), other malignancies (n: 3). Six patients developed porto-spleno-mesenteric venous thrombosis and only 2 of them were symptomatic. Patients were treated with anticoagulation therapy with complete resolution. Analysis identified three main factors associated with thrombosis: spleen diameter (p = 0.03), myeloproliferative disorder (p = 0.02), intraoperative platelet transfusion (p = 0.002) and intraoperative red blood cells transfusion (p = 0.009). Conclusion: Standardized postoperative screening allows prompt diagnosis and treatment of porto-spleno-mesenteric venous thrombosis even in asymptomatic cases. Patient with splenomegaly and affected by myeloproliferative disorder have a greater risk to develop this complication.

Association between severe acute malnutrition in childhood and hematological disorders in adulthood: the Lwiro follow-up study in the Eastern Democratic Republic of the Congo.

BACKGROUND: Despite growing evidence on the short-term deleterious effects of severe acute malnutrition (SAM) in childhood on hematopoiesis, little is known about the long-term hematological effects of SAM in low-income countries (LICs). Our study explored the association between childhood SAM and hematological disorders in adults 11 to 30 years after post-SAM nutritional rehabilitation. METHODS: This follow up study investigated 97 adults (mean age 32 years) treated for SAM during childhood in eastern Democratic Republic of the Congo (DRC) between 1988 and 2007. Participants were compared to 97 aged- and sex-matched adult controls living in the same community with no history of SAM. Outcomes of interest were hematological characteristics and disorders in adulthood, assessed by various biological markers. Logistic and linear regression models were used to estimate the association between SAM in childhood and risk of hematological abnormalities. RESULTS: Compared to the unexposed, the exposed had higher mean white blood cells (/µl) [+ 840 (179 to 1501), p = 0.013], neutrophils [+ 504 (83 to 925), p = 0.019] and platelets (*103) [11.9 (8.1 to 17.9), p = 0.038] even after adjustment for food consumption in adulthood. No difference was observed in red blood cells (RBC), hemoglobin and erythrocytes parameters. With regard to the risk of hematological disorders, in contrast to the unexposed, exposed subjects had a risk of leukocytosis approximately three times higher [adjusted OR (95% CI): 2.98 (1.01 to 8.79), p = 0.048]. No difference was observed in terms of anemia, leukopenia, increased platelets and thrombocytopenia between the 2 groups. CONCLUSION: Adults with a history of SAM in childhood have hematological characteristics that would be markers associated with chronic low-grade inflammatory or infectious diseases in an environment with no nutritional transition. Larger cohort studies with bone marrow analyses could provide further understanding of the impact of SAM on the overall hematological profile in adult life.

Case Report: Mycosis fungoides as an exclusive manifestation of common variable immunodeficiency in a family with a NFKB2 gene mutation.

Background: Common variable immunodeficiency disorders (CVIDs), which are primary immunodeficiencies characterized by the failure of primary antibody production, typically present with recurrent bacterial infections, decreased antibody levels, autoimmune features, and rare atypical manifestations that can complicate diagnosis and management. Although most cases are sporadic, approximately 10% of the patients may have a family history of immunodeficiency. Genetic causes involving genes related to B-cell development and survival have been identified in only a small percentage of cases. Case presentation: We present the case of a family with two brothers who presented with mycosis fungoides as an exclusive symptom of a common variable immunodeficiency disorder (CVID). Whole-exome sequencing of the index patient revealed a pathogenic variant of the NFKB2 gene. Based on this diagnosis and re-evaluation of other family members, the father and brother were diagnosed with this rare immune and preneoplastic syndrome. All CVID-affected family members presented with mycosis fungoides as their only symptom, which is, to the best of our knowledge, the first case to be reported. Conclusion: This case highlights the importance of high-throughput sequencing techniques for the proper diagnosis and treatment of hereditary hematological disorders.

Exploring the Link between Maternal Hematological Disorders during Pregnancy and Neurological Development in Newborns: Mixed Cohort Study.

Maternal hematological disorders during pregnancy may pose a risk to the neurological development of newborns. To investigate the association between maternal hematological disorders during pregnancy and neurological outcomes in newborns, this mixed cohort study was conducted on 200 pregnant women diagnosed with hematological disorders during pregnancy. Some cases have been identified in the past who have completed the pregnancy in full, as well as cases in pregnancy. Currently, the children of all mothers have been followed up to evaluate the neurological outcomes of the children at the age of three months. Logistic regression analysis was used to determine the association between maternal hematological disorders and neurological outcomes in newborns. Children born to mothers with hematological disorders had a higher risk of developmental delays (OR = 1.50, 95% CI = 0.90-2.50), cognitive impairments (OR = 1.80, 95% CI = 1.20-2.70), and motor impairments (OR = 1.60, 95% CI = 1.00-2.50) compared to children born to mothers without hematological disorders. Hemophilia was associated with the highest risk of neurological outcomes (developmental delay: OR = 2.80, 95% CI = 1.60-4.90; cognitive impairment: OR = 3.20, 95% CI = 2.00-5.10; motor impairment: OR = 2.60, 95% CI = 1.50-4.60). Conclusion: Our study suggests that maternal hematological disorders during pregnancy may increase the risk of negative neurological consequences in newborns. Further research is needed to identify potential mechanisms and explore preventive measures.

Identification of a robust DNA methylation signature for Fanconi anemia.

Fanconi anemia (FA) is a clinically variable and genetically heterogeneous cancer-predisposing disorder representing the most common bone marrow failure syndrome. It is caused by inactivating predominantly biallelic mutations involving >20 genes encoding proteins with roles in the FA/BRCA DNA repair pathway. Molecular diagnosis of FA is challenging due to the wide spectrum of the contributing gene mutations and structural rearrangements. The assessment of chromosomal fragility after exposure to DNA cross-linking agents is generally required to definitively confirm diagnosis. We assessed peripheral blood genome-wide DNA methylation (DNAm) profiles in 25 subjects with molecularly confirmed clinical diagnosis of FA (FANCA complementation group) using Illumina's Infinium EPIC array. We identified 82 differentially methylated CpG sites that allow to distinguish subjects with FA from healthy individuals and subjects with other genetic disorders, defining an FA-specific DNAm signature. The episignature was validated using a second cohort of subjects with FA involving different complementation groups, documenting broader genetic sensitivity and demonstrating its specificity using the EpiSign Knowledge Database. The episignature properly classified DNA samples obtained from bone marrow aspirates, demonstrating robustness. Using the selected probes, we trained a machine-learning model able to classify EPIC DNAm profiles in molecularly unsolved cases. Finally, we show that the generated episignature includes CpG sites that do not undergo functional selective pressure, allowing diagnosis of FA in individuals with reverted phenotype due to gene conversion. These findings provide a tool to accelerate diagnostic testing in FA and broaden the clinical utility of DNAm profiling in the diagnostic setting.

A clinical analysis of Candida tropicalis bloodstream infections associated with hematological diseases, and antifungal susceptibility: a retrospective survey.

Summary objective: To assess the clinical features and outcomes of hematological disease patients with Candida tropicalis bloodstream infections and determine the antifungal susceptibility of C. tropicalis. Methods: This is a retrospective, single-center, observational study conducted in the Department of Hematology at The First Affiliated Hospital of Guangxi Medical University from January 2013 to December 2021. A total of 26 hematological disease patients with C. tropicalis bloodstream infections were enrolled, and their clinical features, treatment plans, and prognoses were assessed. Univariate analysis was performed by Kaplan-Meier analysis and multivariate analysis was conducted using a Cox regression model. The antifungal susceptibility of C. tropicalis was determined from patient blood cultures. Results: The patients had a mean age of 35 years (range: 10-65 years), 50% were male (13/26) and 88.5% had hematologic malignancies (23/26) while the remaining three patients included two cases of severe aplastic anemia and one case of ß-thalassemia. All patients had neutropenia. Seven patients were initially given azole alone (26.9%), five of whom failed treatment and died (71.4%). Fifteen patients were treated with echinocandin (57.7%), three of whom failed treatment and died (20.0%), and eight patients were treated with amphotericin B (30.8%), two of whom failed treatment and died (25.0%). The total and attributable mortality rates were 42.3 and 34.6%, respectively. Univariate analysis showed that there are six risk factors for attributable deaths among hematological disease patients with C. tropicalis blood infections. These risk factors included septic shock, Pitt bacteremia scores ≥4, procalcitonin levels ≥10 ng/mL, positive plasma (1,3)- ß-D glucan assay, serum albumin levels <30.0 g/L, time from fever to antifungal treatment initiation ≥5 days and time between neutropenia and antifungal treatment ≥10 days. Moreover, skin and mucosal infections and a treatment schedule that included amphotericin B and drug combinations are protective factors for attributable deaths. Multivariate analysis showed that septic shock (p = 0.006) was an independent risk factor for attributable death. All isolates were sensitive to flucytosine and amphotericin B. The intermediate or resistance of C. tropicalis to fluconazole, itraconazole and voriconazole were 41.7, 50, and 41.7%, respectively. Conclusion: Hematological disease patients with C. tropicalis bloodstream infections had a high mortality rate, and early antifungal therapy significantly reduced mortality. Candida tropicalis was highly resistant to azole drugs and sensitive to flucytosine and amphotericin B. According to our study, the preferred agent is amphotericin B and drug combinations should be considered for severe infections.

Identifying childhood leukemia with an excess of hematological malignancies in first-degree relatives in Brazil.

Background: Familial aggregation in childhood leukemia is associated with epidemiological and genomic factors. Albeit epidemiological studies on the familial history of hematological malignancies (FHHMs) are scarce, genome-wide studies have identified inherited gene variants associated with leukemia risk. We revisited a dataset of acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML) patients to explore the familial aggregation of malignancies among their relatives. Methods: A series of 5,878 childhood leukemia (≤21 years of age) from the EMiLI study (2000-2019) were assessed. Lack of well-documented familial history of cancer (FHC) and 670 cases associated with genetic phenotypic syndromes were excluded. Leukemia subtypes were established according to World Health Organization recommendations. Logistic regression-derived odds ratios (ORs) and 95% confidence intervals (CIs) were performed and adjusted by age as a continuous variable, where ALL was the reference group for AML and conversely. The pedigree of 18 families with excess hematological malignancy was constructed. Results: FHC was identified in 472 of 3,618 eligible cases (13%). Ninety-six of the 472 patients (20.3%) had an occurrence of FHHMs among relatives. Overall, FHC was significantly associated with AML (OR, 1.36; 95% CI, 1.01-1.82; p = 0.040). Regarding the first-degree relatives, the OR, 2.92 95% CI,1.57-5.42 and the adjOR, 1.16 (1.03-1.30; p0.001) were found for FHC and FHHM, respectively. Conclusion: Our findings confirmed that AML subtypes presented a significant association with hematological malignancies in first-degree relatives. Genomic studies are needed to identify germline mutations that significantly increase the risk of developing myeloid malignancies in Brazil.

Analysis and clinical characteristics of acute myeloid leukemia developing with prior or concurrent tumors in non cyto- or radiotherapy exposure patients in a single center.

ABSTRACTAcute myeloid leukemia (AML) that develops along with prior or concurrent tumors without previous cyto- or radiotherapy (pc-AML) is an essential subset of AML but is often ignored and ambiguous. The biological and genetic characteristics of pc-AML remain largely unknown. Moreover, it is unclear whether pc-AML should be treated as de novo or secondary AML, whereas most clinical trials exclude it due to comorbidities. We performed a retrospective study of 50 patients with multiple neoplasms over five years. We focused on characteristics, treatment regimens, response rate, and prognosis of pc-AML, compared with therapy-related AML (tAML) and AHD-AML (AML discovered following prior hematologic disorders) as controls. We report the first detailed distribution of secondary tumors associated with hematological disorders. The incidence of pc-AML was 30% of all multiple neoplasms, and it was predominantly found in male and older participants. Nearly three-quarters of gene mutations affected epigenetic regulation and signaling pathways, and NPM1, ZRSR2, and GATA2 occurred exclusively in pc-AML. No significant differences were in CR, and pc-AML had an inferior OS similar to that of tAML and AHD-AML. More patients received hypomethylation agents (HMAs) in combination with venetoclax (HMAs + VEN) than intensive chemotherapy (IC) (65.7% vs 31.4%), and there was a trend toward improved OS in HMAs + VEN-based than in IC-based patients, whose 2-year estimated OS times were 53.6% and 35.0%, respectively. In conclusion, our results collectively support pc-AML as a biologically and genetically distinct entity with high-risk and dismal outcomes, and HMAs in combination with venetoclax-based regimens may benefit patients with pc-AML.

VEXAS Syndrome-Review.

VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome is a newly defined refractory adult-onset autoinflammatory syndrome caused by somatic mutations in the ubiquitin-like modifier-activating enzyme 1 (UBA1) gene in hematopoietic stem and progenitor cells, resulting in a shift in UBA1 isoform expression. Thus, patients develop a spectrum of systemic inflammatory manifestations and hematologic symptoms. To date, patients respond poorly to immune suppressive drugs, except high-dose glucocorticoids, and no treatment guidelines have been established. Given the high mortality rate, VEXAS syndrome needs to be taken seriously by physicians in all specialties. This article aims to describe the key features, pathogenesis, and clinical manifestations of VEXAS syndrome to better understand the targeted treatment and improve the prognosis of VEXAS syndrome.

Genetic analysis and functional study of a novel ABCG5 mutation in sitosterolemia with hematologic disease.

Sitosterolemia is a rare autosomal recessive hereditary disease caused by loss-of-function genetic mutations in either ATP-binding cassette subfamily G member 5 or member 8 (ABCG5 or ABCG8). Here, we investigate novel variants in ABCG5 and ABCG8 that are associated with the sitosterolemia phenotype. We describe a 32-year-old woman with hypercholesterolemia, tendon and hip xanthomas, autoimmune hemolytic anemia and macrothrombocytopenia from early life, which make us highly suspicious of the possibility of sitosterolemia. A novel homozygous variant in ABCG5 (c.1769C>A, p.S590X) was identified by genomic sequencing. We also examined the lipid profile, especially plant sterols levels, using gas chromatography-mass spectrometry. Functional studies, including western blotting and immunofluorescence staining, showed that the nonsense mutation ABCG5 1769C>A hinders the formation of ABCG5 and ABCG8 heterodimers and the function of transporting sterols. Our study expands the knowledge of variants in sitosterolemia and provides diagnosis and treatment recommendations.

Multicentric Castleman Disease and Concurrent Hematological Disorders: The Occurrence of Plasmacytoma and the Hypotheses Arising from Literature Review.

The concomitant presence of Castleman disease (CD) with other hematological pathology is an event described in the literature with increasing frequency, able to modify the diagnostic and curative approach in such patients. Very few studies in the literature describe the association of CD with concomitant neoplastic diseases; the most frequent are Kaposi's sarcomas (especially in HIV and human herpes virus-8-positive patients) and lymphoproliferative disorders, such as lymphomas. Instead, since the association with plasma cell diseases such as multiple myeloma and plasmacytoma is infrequent, there is a lack of literature. This manuscript aimed to revise the literature by describing a rare case of CD and plasmacytoma and attempting to explain the underlying triggering mechanisms.