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Dysregulated Wnt/ß-catenin signal transduction is implicated in initiation, propagation, and poor prognosis in AML. Epigenetic inactivation is central to Wnt/ß-catenin hyperactivity, and Wnt/ß-catenin inhibitors are being investigated as targeted therapy. Dysregulated Wnt/ß-catenin signaling has also been linked to accelerated aging. Since AML is a disease of old age (>60 yrs), we hypothesized age-related differential activity of Wnt/ß-catenin signaling in AML patients. We probed Wnt/ß-catenin expression in a series of AML in the elderly (>60 yrs) and compared it to a cohort of pediatric AML (<18 yrs). RNA from diagnostic bone marrow biopsies (n = 101) were evaluated for key Wnt/ß-catenin molecule expression utilizing the NanoString platform. Differential expression of significance was defined as >2.5-fold difference (p < 0.01). A total of 36 pediatric AML (<18 yrs) and 36 elderly AML (>60 yrs) were identified in this cohort. Normal bone marrows (n = 10) were employed as controls. Wnt/ß-catenin target genes (MYC, MYB, and RUNX1) showed upregulation, while Wnt/ß-catenin inhibitors (CXXR, DKK1-4, SFRP1-4, SOST, and WIFI) were suppressed in elderly AML compared to pediatric AML and controls. Our data denote that suppressed inhibitor expression (through mutation or hypermethylation) is an additional contributing factor in Wnt/ß-catenin hyperactivity in elderly AML, thus supporting Wnt/ß-catenin inhibitors as potential targeted therapy.
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Adenosine deaminase 2 deficiency (DADA2), a rare and potentially fatal systemic autoinflammatory disease, is characterized by low or lack of ADA2 activity due to ADA2 mutations. DADA2 symptoms are variable and include vasculitis, immunodeficiency, and cytopenia. Minimal data are available from Saudi Arabia. This retrospective study conducted at seven major tertiary medical centers examined the phenotypic and genotypic variabilities, clinical and diagnostic findings, and treatment outcomes among 20 Saudi patients with DADA2 from 14 families. The median age of the study cohort was 9.5 years (4-26 years). The clinical presentation was before the age of 5 months in 25% of patients. Homozygous c.1447-1451del mutation was the most frequent ADA2 alteration (40%), followed by c.882-2A:G (30%). All tested patients exhibited absent or near-absent ADA2 activity. Phenotypic manifestations included stroke (40%), hematological abnormalities (95%), lymphoproliferation (65%), and recurrent infection (45%). Five and three patients had extracranial vasculitis features and Hodgkin lymphoma, respectively. Atypical manifestations included growth retardation (30%) and transverse myelitis. Anti-tumor necrosis factor (anti-TNF) therapy was the main treatment. Some patients underwent blood transfusion, splenectomy, cyclosporine and colony-stimulating factor therapies, and hematopoietic stem cell transplantation due to anti-TNF therapy failure. Fulminant hepatitis and septic multiorgan failure caused mortality in three patients. Thus, this study revealed the variability in the molecular and clinical characteristics of DADA2 in the study cohort with predominant aberrant hematological and immunological characteristics. Consensus diagnostic criteria will facilitate early diagnosis and treatment. Additionally, disease registries or large prospective studies are needed for evaluating rare disease complications, such as cancer.
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Adenosina Desaminase , Vasculite , Humanos , Arábia Saudita , Estudos Retrospectivos , Inibidores do Fator de Necrose Tumoral , Peptídeos e Proteínas de Sinalização Intercelular/genética , Genótipo , Fenótipo , Vasculite/etiologia , Mutação/genéticaRESUMO
Plasmablastic lymphoma (PBL) is a rare and aggressive B-cell lymphoma with overlapping characteristics with diffuse large B-cell lymphoma (DLBCL) and multiple myeloma. Hyperactive Wnt signaling derails homeostasis and promotes oncogenesis and chemoresistance in DLBCL and multiple myeloma. Evidence suggests active cross-talk between the Wnt and RAS pathways impacting metastasis in solid cancers in which combined targeted therapies show effective results. Recent genomic studies in PBL demonstrated a high frequency of mutations linked with the RAS signaling pathway. However, the role of RAS and Wnt signaling pathway molecule expression in PBL remained unknown. We examined the expression of Wnt and RAS pathway-related genes in a well-curated cohort of PBL. Because activated B cells are considered immediate precursors of plasmablasts in B cell development, we compared this data with activated B-cell type DLBCL (ABC-DLBCL) patients, employing NanoString transcriptome analysis (770 genes). Hierarchical clustering revealed distinctive differential gene expression between PBL and ABC-DLBCL. Gene set enrichment analysis labeled the RAS signaling pathway as the most enriched (37 genes) in PBL, including upregulating critical genes, such as NRAS, RAF1, SHC1, and SOS1. Wnt pathway genes were also enriched (n = 22) by gene set enrichment analysis. Molecules linked with Wnt signaling activation, such as ligands or targets (FZD3, FZD7, c-MYC, WNT5A, WNT5B, and WNT10B), were elevated in PBL. Our data also showed that, unlike ABC-DLBCL, the deranged Wnt signaling activity in PBL was not linked with hyperactive nuclear factor κB and B-cell receptor signaling. In divergence, Wnt signaling inhibitors (CXXC4, SFRP2, and DKK1) also showed overexpression in PBL. The high expression of RAS signaling molecules reported may indicate linkage with gain-in-function RAS mutations. In addition, high expression of Wnt and RAS signaling molecules may pave pathways to explore benefiting from combined targeted therapies, as reported in solid cancer, to improve prognosis in PBL patients.
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Linfoma Difuso de Grandes Células B , Mieloma Múltiplo , Linfoma Plasmablástico , Humanos , Via de Sinalização Wnt/genética , Linfoma Difuso de Grandes Células B/patologia , Expressão Gênica , Proteínas de Ligação a DNA/genética , Fatores de Transcrição/genéticaRESUMO
Biallelic changes in the ZNFX1 gene have been recently reported to cause severe familial immunodeficiency. Through a search of our bio/databank with information from genetic testing of >55 000 individuals, we identified nine additional patients from seven families with six novel homozygous ZNFX1 variants. Consistent with the previously described phenotype, our patients suffered from monocytosis, thrombocytopenia, hepatosplenomegaly, recurrent infections, and lymphadenopathy. The two most severely affected probands also had renal involvement and clinical presentations compatible with hemophagocytic lymphohistiocytosis. The disease was less lethal among our patients than previously reported. We identified two missense changes, two variants predicted to result in complete protein loss through nonsense-mediated decay, and two frameshift changes that likely introduce a truncation. Our findings (i) independently confirm the role of ZNFX1 in primary genetic immunodeficiency, (ii) expand the genetic and clinical spectrum of ZNFX1-related disease, and (iii) illustrate the utility of large, well-curated, and continually updated genotype-phenotype databases in resolving molecular diagnoses of patients with initially negative genetic testing findings.
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Alelos , Antígenos de Neoplasias/genética , Doenças Hematológicas/diagnóstico , Doenças Hematológicas/genética , Mutação , Doenças da Imunodeficiência Primária/diagnóstico , Doenças da Imunodeficiência Primária/genética , Mapeamento Cromossômico , Biologia Computacional/métodos , Análise Mutacional de DNA , Bases de Dados Genéticas , Fácies , Estudos de Associação Genética , Predisposição Genética para Doença , Homozigoto , Humanos , Linhagem , FenótipoRESUMO
BACKGROUND: Hemophagocytic lymphohistiocytosis (HLH) is a rare and potentially fatal syndrome that is characterized by strong activation of the immune system from hyperinflammatory cytokines. Symptoms of HLH patients include fever, hepatosplenomegaly, cytopenia, and hyperferritinemia. Inherited HLH is classified as primary, whereas secondary HLH (sHLH) occurs when acquired from non-inherited reasons that include severe infection, immune deficiency syndrome, autoimmune disorder, neoplasm, and metabolic disorder. Wolman's disease (WD) is a rare and fatal infantile metabolic disorder caused by lysosomal acid lipase deficiency, that exhibits similar clinical signs and symptoms as HLH. This paper reports the case of an infant diagnosed with WD and who presented with sHLH. CASE PRESENTATION: A 4-month-old infant presenting with hepatosplenomegaly, failure to thrive, and other abnormalities. WD diagnosis was confirmed by the presence of the LIPA gene homozygous deletion c.(428 + 1_967-1)_(*1_?)del. The infant also met the HLH-2004 diagnostic criteria. CONCLUSIONS: Metabolic disorder such as WD should be investigated in infants fulfilling the HLH criteria to diagnose the underlying condition. More studies are needed to understand the link between WD and sHLH and to identify appropriate therapies.
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Linfo-Histiocitose Hemofagocítica , Doença de Wolman , Homozigoto , Humanos , Lactente , Linfo-Histiocitose Hemofagocítica/etiologia , Linfo-Histiocitose Hemofagocítica/genética , Arábia Saudita , Deleção de Sequência , Doença de Wolman/complicações , Doença de Wolman/diagnóstico , Doença de Wolman/genéticaRESUMO
Genetic aberrations in the epigenome are rare in pediatric AML, hence expression data in epigenetic regulation and its downstream effect is lacking in childhood AML. Our pilot study screened epigenetic modifiers and its related oncogenic signal transduction pathways concerning clinical outcomes in a small cohort of pediatric AML in KSA. RNA from diagnostic BM biopsies (n = 35) was subjected to expression analysis employing the nCounter Pan-Cancer pathway panel. The patients were dichotomized into low ASXL1 (17/35; 49%) and high ASXL1 (18/35; 51%) groups based on ROC curve analysis. Age, gender, hematological data or molecular risk factors (FLT3 mutation/molecular fusion) exposed no significant differences across these two distinct ASXL1 expression groups (P > 0.05). High ASXL1 expression showed linkage with high expression of other epigenetic modifiers (TET2/EZH2/IDH1&2). Our data showed that high ASXL1 mRNA is interrelated with increased BRCA1 associated protein-1 (BAP1) and its target gene E2F Transcription Factor 1 (E2F1) expression. High ASXL1 expression was associated with high mortality {10/18 (56%) vs. 1/17; (6%) P < 0 .002}. Low ASXL1 expressers showed better OS {740 days vs. 579 days; log-rank P= < 0.023; HR 7.54 (0.98-54.1)}. The association between high ASXL1 expression and epigenetic modifiers is interesting but unexplained and require further investigation. High ASXL1 expression is associated with BAP1 and its target genes. Patients with high ASXL1 expression showed poor OS without any association with a conventional molecular prognostic marker.
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Epigênese Genética , Perfilação da Expressão Gênica , Regulação Leucêmica da Expressão Gênica , Leucemia Mieloide Aguda , Proteínas Repressoras , Proteínas Supressoras de Tumor , Ubiquitina Tiolesterase , Criança , Pré-Escolar , Intervalo Livre de Doença , Feminino , Humanos , Lactente , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/metabolismo , Leucemia Mieloide Aguda/mortalidade , Masculino , Proteínas Repressoras/biossíntese , Proteínas Repressoras/genética , Taxa de Sobrevida , Proteínas Supressoras de Tumor/biossíntese , Proteínas Supressoras de Tumor/genética , Ubiquitina Tiolesterase/biossíntese , Ubiquitina Tiolesterase/genéticaRESUMO
Mantle cell lymphoma (MCL) is an aggressive disease with frequent relapse. Targeted therapies against B-cell receptor (BCR) molecules have demonstrated improved outcomes in relapsed cases. However, clinical responses are slow and selective, with failure to attain complete remission in a significant subset of patients. Complex interaction of BCR signal transduction with toll-like receptor (TLR) and other pathways in MCL remains unknown, thus averting progress in development of targeted therapies. We have performed detailed digital quantification of BCR/TLR signalling molecules and their effector pathways in a cohort (n = 81) of MCL patients and correlated these data with overall survival. Hierarchical clustering model based on BCR/TLR genes revealed two distinct (BCRhigh and BCRlow ) subsets of patients (n = 32; 40%) with significant differences in expression (>1.5-fold change; p < 0.05). Higher levels of BTK/SYK/BLNK/CARD11/PLCG signalosome and lower expression of MALT1/BCL10 genes suggested tonic pattern of BCR activation. Amplified expression of TLR6/TLR7/TLR9 was noted in concert with hyper-responsiveness of BCR machinery. MYD88, a key TLR adaptor molecule, was not upregulated in any of these clusters, which may suggest a 'cross-talk' between BCR and TLR pathways. In sync with BCR/TLR signalling, we recorded significantly enhanced expression of genes associated with NF-kB pathway in BCRhigh subset of MCL patients. On univariate analysis, the BCRhigh patients showed a trend towards inferior clinical response to a standardized treatment protocol, compared with the BCRlow group (log rank, p = 0.043). In conclusion, we have identified hyperactive BCR/TLR signalling pathways and their effector downstream targets in a subset of MCL patients and associated it with poor clinical outcomes. Our study provides quantitative evidence at RNA expression level of possible concomitant collaboration between TLR and BCR signalling molecules in MCL. These data will provide further insights for future functional studies and, hence, development of targeted therapies for MCL patients. Copyright © 2015 John Wiley & Sons, Ltd.
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Linfócitos B/metabolismo , Regulação Neoplásica da Expressão Gênica , Linfoma de Célula do Manto/metabolismo , Receptores de Antígenos de Linfócitos B/metabolismo , Receptores Toll-Like/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Análise por Conglomerados , Estudos de Coortes , Biologia Computacional , Feminino , Perfilação da Expressão Gênica , Humanos , Linfoma de Célula do Manto/mortalidade , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Indução de Remissão , Transdução de Sinais , Resultado do Tratamento , Regulação para CimaRESUMO
BACKGROUND: The simultaneous Occurrence of chronic lymphocytic leukemia (CLL) and acute myeloid leukemia (AML) has been rarely reported. Most of these cases have been occurring more frequently as a secondary event in patients receiving chemotherapeutic agents for CLL. CASE PRESENTATION: We describe a case of a 77-year-old man who presented with fatigue, pallor and lower limb pain and weakness. Initial laboratory studies showed Hb 7.7 g/dl, WBC 279.6 × 10(9)/1, PLT 143× 10(9)/1. The peripheral blood (PB) smear examination showed circulating blast cells (20 %) cells and 50 % lymphocytes, with smudge cells. A bone marrow examination showed infiltration by two discrete abnormal cell populations, one represents the leukemic blast cells (60 %) and the other represents small mature lymphocytes (30 %). The immunologic phenotype of blasts was characterized by the co-expression of CD13, CD33, CD14, CD4, CD15, CD64, HLA-DR, CD11c. Lymphocytes were characterized by a typical CLL immunophenotype: CD19+, CD5+, CD23+, CD20+ (dim) and negative for FMC7, CD34, CD10 and TdT. Cytogenetic studies were negative for CLL and AML panels. PCR assays for AML specific genetic abnormalities were negative. Immunoglobulin gene analysis established the clonal nature of the B-cell expansion. A final diagnosis of concomitant CLL and AML(FAB: M5) was made. CONCLUSION: We have reported a case in which there was simultaneous presentation of AML and CLL. Both forms of leukemia were well documented by morphology, cytometric analysis and molecular studies. Our findings support the idea that this rare concurrence of AML and untreated CLL may represent two separate disease processes.
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Leucemia Linfocítica Crônica de Células B/diagnóstico , Leucemia Mieloide Aguda/diagnóstico , Segunda Neoplasia Primária/diagnóstico , Idoso , Biomarcadores , Biópsia , Humanos , Imuno-Histoquímica , Imunofenotipagem , Leucemia Linfocítica Crônica de Células B/metabolismo , Leucemia Mieloide Aguda/metabolismo , Contagem de Leucócitos , Linfócitos/metabolismo , Linfócitos/patologia , Masculino , Segunda Neoplasia Primária/metabolismoAssuntos
COVID-19/complicações , Linfo-Histiocitose Hemofagocítica/virologia , SARS-CoV-2/isolamento & purificação , Anti-Inflamatórios/uso terapêutico , Antineoplásicos Fitogênicos/uso terapêutico , COVID-19/virologia , Criança , Dexametasona/uso terapêutico , Etoposídeo/uso terapêutico , Feminino , Humanos , Imunossupressores/uso terapêutico , Inflamação/tratamento farmacológico , Inflamação/etiologia , Inflamação/virologia , Proteína Antagonista do Receptor de Interleucina 1/uso terapêutico , Linfo-Histiocitose Hemofagocítica/tratamento farmacológico , Linfo-Histiocitose Hemofagocítica/etiologia , SARS-CoV-2/efeitos dos fármacos , Tratamento Farmacológico da COVID-19RESUMO
Primary diffuse large B-cell lymphoma of the central nervous system (CNS DLBCL) is a distinct and aggressive lymphoma that is confined to CNS. Since, central nervous system is barrier-protected and immunologically silent; role of TLR/BCR signaling in pathogenesis and biology of CNS DLBCL is intriguing. Genomic mutations in key regulators of TLR/BCR signaling pathway (MYD88/CD79B/CARD11) have recently been reported in this disease. These observations raised possible implications in novel targeted therapies; however, expression pattern of molecules related to TLR/BCR pathways in this lymphoma remains unknown. We have analyzed the expression of 19 genes encoding TLR/BCR pathways and targets in CNS DLBCLs (n = 20) by Nanostring nCounter™ analysis and compared it with expression patterns in purified reactive B-lymphocytes and systemic diffuse large B cell lymphoma (DLBCL) (n = 20). Relative expression of TLR4, TLR5, TLR9, CD79B and BLNK was higher in CNS DLBCLs than in control B-lymphocytes; where as TLR7, MALT1, BCL10, CD79A and LYN was lower in CNS DLBCLs (P < 0.0001). When compared with systemic DLBCL samples, higher expression of TLR9, CD79B, CARD11, LYN and BLNK was noted in CNS DLBCL (>1.5 fold change; P < 0.01). The B cell receptor molecules like BLNK and CD79B were also associated with higher expression of MYD88 dependent TLRs (TLR4/5/9). In conclusion, we have shown over expression of TLR/BCR related genes or their targets, where genomic mutations have commonly been identified in CNS DLBCL. We have also demonstrated that TLR over expression closely relate with up regulation of genes associated with BCR pathway like CD79B/BLNK and CARD11, which play an important role in NF-kB pathway activation. Our results provide an important insight into the possibility of TLR and/or B-cell receptor signaling molecules as possible therapeutic targets in CNS DLBCL.
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Neoplasias do Sistema Nervoso Central/metabolismo , Linfoma Difuso de Grandes Células B/metabolismo , Receptores de Antígenos de Linfócitos B/metabolismo , Receptores Toll-Like/metabolismo , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , HumanosRESUMO
COVID 19 is a serious infection that originated in Wuhan, China and has resulted in worldwide morbidity and mortality. It continues to be a major health concern in 2022, being associated with multiorgan failure. Although the pathophysiology of the disease and its complications are not well understood, it is believed that a cytokine storm, triggered by complement activation may be responsible for the severity and complications of the disease. As of now, there is no definitive treatment available. Hematological changes associated with COVID-19 include lymphopenia, anemia, thrombocytopenia, disseminated intravascular coagulopathy, and thrombosis. Paroxysmal nocturnal hemoglobinuria (PNH), on the other hand, is an acquired clonal hematopoietic stem cell disorder that occurs due to an acquired PIG-A mutation affecting the hematopoietic stem cells. Interestingly, PNH exhibits some clinical and laboratory manifestations like those seen in COVID-19. In this report, we present a rare case of PNH that developed following a COVID-19 infection.
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Human leukocyte antigens (HLA) diversity has a tremendous impact on shaping the transplantation practices, transfusion-associated graft versus host disease prevention strategies, and host-pathogen interactions. Here, we conducted a retrospective study of HLA class I and class II homozygosity at allelic and haplotype levels in unrelated individuals genotyped from 2012 to 2016 in a tertiary hospital in the capital of Saudi Arabia. Among 5,000 individuals, 2,773 individuals meet inclusion criteria and were retrospectively analyzed for HLA-A, -B, -C-DRB1, and -DQB1 homozygosity at allelic and haplotype levels. HLA molecular typing was performed using a commercial reverse sequence-specific oligonucleotide (rSSO) kit. We were able to identify 15 HLA-A, 20 HLA-B, 11 HLA-C, 13 HLA-DRB1, and five HLA-DQB1 homozygous alleles demonstrating a very low genetic diversity in the Saudi population. The highest homozygosity in HLA class I was found in locus C followed by A and B (20.3% > 16.1% > 15.5%; p < 0.001) where the most homozygote alleles were A*02 (9.2%), B*51 and B*50 (5.7% and 3.7%), and C*07, C*06, and C*15 (7.2%, 5.48%, and 3.3%) and in HLA class II, the highest homozygosity was found in locus DQB1 compared to DRB1 (31.71% > 19.2%; p < 0.001), with the most common homozygote alleles being DRB1*07 and DRB1*04 (5.33% and 4.2%) and DQB1*02, DQB1*06, and DQB1*03 (13.55%, 7.92%, and 7.64%). The frequency of finding an individual with one homozygote allele was (24.6%), two homozygote alleles (13.5%), three homozygote alleles (4.7%), four homozygote alleles (3.4%), and five alleles were (4.8%). The most frequent homozygote haplotypes are A*23â¼C*06â¼B*50â¼DRB1*07â¼DQB1*02 and A*02â¼C*06â¼B*50â¼DRB1*07â¼DQB1*02. This study shows low diversity of both class I and II alleles and haplotypes in the Saudi population, which would have a significant impact on shaping the transplantation practices, transfusion-associated graft versus host disease prevention strategies, and host-pathogen interactions.
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Plasmablastic lymphoma (PBL) is a rare subtype of non-Hodgkin's lymphoma that is associated with acquired immunodeficiency syndrome (AIDS), characterized by its association with Epstein-Barr virus (EBV), aggressive nature, and plasmacytic/plasmablastic differentiation. PBL remains a therapeutic and diagnostic challenge. Diagnosis of PBL by fine-needle aspiration cytology (FNAC) is reported infrequently. We herein describe the cytodiagnosis of a rare case of HIV-negative PBL in a 58-year-old man without EBV infection presented by parotid swelling. The current case study highlights the cytomorphologic features that may help to distinguish PBL from other mimics. However, although the cytomorphologic features may suggest PBL, a definitive diagnosis requires additional studies including tissue biopsy and immunohistochemistry, in addition to biochemical investigations and radiological workup to establish the diagnosis and exclude similar conditions. In conclusion, FNAC is a very useful, simple, rapid and reliable procedure for diagnosis of the lymphoma. FNAC provided the earliest clue to diagnosis of PBL, which was later confirmed by tissue biopsy.
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The Novel Coronavirus 2019 (SARSCoV- 2), which was first reported on in Wuhan, China, in late December 2019, causes a respiratory illness called COVID- 19 Disease. COVID-19 is most likely causing a hypercoagulable state, however the prevalence of acute venothromboembolism is still unknown. Limited data suggest pulmonary microvascular thrombosis may play a role in progressive respiratory failure. Here, we report a case of a child with an unusual presentation of COVID-19 presented initially by dry cough without fever and complicated by massive acute pulmonary embolism and lung infarction and treated successfully by hydroxychloroquine and azithromycin, in addition to anticoagulant therapy.
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Advances in pediatric cancer treatment and dramatic improvement in long-term survival have made health-related quality of life (HRQOL) a priority. This study describes the HRQOL of Saudi children on cancer treatment, given the paucity of data on the subject. Parents of children undergoing cancer treatment between the ages of 2 and 12 years enrolled to answer the Arabic version of the parent proxy report PedsQL™ 3.0 cancer module. The module items were reverse-scored to a linear scale from 0 to 100, in which higher scores indicated a better HRQOL. Of the 95 study participants, 61 (64.2%) were hematological malignancies and 34 (35.8%) solid malignancies. The mean score of our sample's total HRQOL was 72.3, which is in line with the results of similar studies worldwide. The lowest scores were observed for procedural anxiety (60.14), perceived physical appearance (67.37), and treatment anxiety (67.58), while the highest were for communication (80.21), nausea (78.32), and cognitive problems (78.32). Significant associations were reported between the patients aged younger than 5 years and procedural anxiety, those aged 5 years or older and perceived physical appearance, and frequent hospital visits and worry. Healthcare professionals should consider the poor HRQOL sub-scales and their associated risks to improve treatment outcomes.
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INTRODUCTION: Iron deficient erythropoiesis and Thalassaemia are both associated with microcytic erythropoiesis albeit from different pathological mechanisms. Given the high prevalence of Hemoglobinopathies in the Mediterranean region, discriminating these two conditions is important. Several algorithms using conventional red cell indices have been developed to facilitate diagnosis, however, their diagnostic accuracy is low. The new generation haematology analyzers enabled the use of more innovative parameters such as reticulocyte parameters. We aimed to evaluate the diagnostic performance of the reticulocyte parameters on the Sysmex XN 1000 to distinguish between IDA and Thalassemia in our population. METHODS: We performed a retrospective analysis of blood samples sent to our laboratory for haemoglobin electrophoresis screening. We categorized our cohort into Thalassemia and Iron Deficient patients based on known diagnostic criteria. We analyzed the reticulocyte parameters using receiver operator curve analysis (ROC) and determined the cut off value for each parameter. RESULTS: Reticulocyte parameters most accurate for discriminating IDA from Thalassemia patients was: RET, RET-HE and IRF. The RET-HE had the best statistical significance for IDA patients with AUC = 0.69 for cut off 22.25. The RET-HE for dual positive patients was more accurate with AUC = 0.78 for cut off 21.25. The IRF had the best statistical significance for Alpha Thalassemia with AUC = 0.66 for cut off value 18. CONCLUSION: An IRF cut off below 15.5 and RET-HE cut off below 22.25 was the most accurate variable in predicting IDA with a sensitivity of 59.4% and 68.3%.
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BACKGROUND: Hodgkin lymphoma (HL) is lymphoid neoplasm usually affecting lymphatic system; it accounts 3.6% of cancers in Saudi Arabia. Modern treatment protocols had shown particular success rates in overall-survival (OS) and event-free-survival (EFS). In our study, we reviewed the medical records of 80 pediatric and young adolescent patients diagnosed HL from January 2006 to July 2020, treated at tertiary care hospital in Riyadh, Saudi Arabia. Demographic, clinical, and pathological data were explored. First line therapy was ABVD, COG, COPP, R-CHOP, or radiotherapy alone in 53/80 (66.4%), 24/80 (30%), 1/80 (1.2%), 1/80 (1.2%), or 1/80 (1.2%) patients; respectively. Response assessment was done by CT + / - PET scan after first 2 cycles then every 2 cycle and end of therapy. Another assessment was done if any clinical suspicion of recurrence. RESULTS: Median age 11 (range 3-16) years. Males to females 1.3:1. Seventy-two out of eighty (90%) patients showed first complete remission (CR1) and maintained remission for median 40 (range 7-136) months. Eight out of eighty (10%) patients showed refractory disease. Nineteen patients received salvage therapy (ICE or ESHAP/brentuximab vedotin or gemcitabine/brentuximab vedotin), 14/19 (73.7%) had 2nd complete remission (CR2) for median time 24 (ranged 9-78) months, while 5/19 (26.3%) did not show any response. Five-year OS and EFS were 95% and 75%. Two patients had 2ry malignant neoplasms, one had AML and died, the other had malignant fibrous histocytoma and still alive. None of our patients had fertility problem. Also, they did not experience chronic pulmonary or cardiotoxicity. Classic Hodgkin's lymphoma: nodular sclerosis subtype was more prominent (55%) than mixed cellularity subtype (22.5%), which is similar to several European and US studies, lymphocyte rich (11.25%) and lymphocyte depleted (0%), while nodular lymphocyte predominant Hodgkin's lymphoma (11.25%). CONCLUSIONS: Our study provided unique descriptive study of childhood HL, in Saudi Arabia, with valuable insight into the long-term outcome and late toxicity. Our results are comparable to other studies in the Middle East and European countries.
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Doença de Hodgkin , Adolescente , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Bleomicina/uso terapêutico , Criança , Pré-Escolar , Dacarbazina/uso terapêutico , Doxorrubicina , Feminino , Doença de Hodgkin/diagnóstico , Doença de Hodgkin/epidemiologia , Doença de Hodgkin/terapia , Humanos , Masculino , Recidiva Local de Neoplasia , Arábia Saudita/epidemiologia , Centros de Atenção Terciária , Resultado do Tratamento , Vimblastina/uso terapêuticoRESUMO
Rare pediatric tumors are heterogeneous group containing a variety of histopathological diseases, they represent approximately 10% of all childhood cancers. These rare tumors had a diversity of histology and clinical behaviors that pose different challenges to the investigators. Exploring different pediatric rare tumors. The data were reviewed, retrospectively, through the medical records of seven rare pediatric diseases between 2012 and 2019. Giant cell fibroblastoma (GCF) presented as painless swelling in the trunk, positive for CD34 with PTEN gene mutation. Neuroglial heterotopic tissue presented in 7 days old girl with facial asymmetry and bulging in the oral cavity, maximal de-bulking was done, histopathology was positive for GFAP and S100p. Left side neck mass, surgically excised revealed non-metastatic salivary grand mucoepidermoid carcinoma. Follow up without any chemotherapy or radiotherapy for 5 years with complete remission. Mesenchymal chondrosarcoma (MCS) presented in maxillofacial bones by persistent nasal bleeding, HEY1-NCOA2 fusion gene confirmed the diagnosis. Extra-osseous Ewing sarcoma (EES) presented as rubbery painless swelling in the scalp with fusion transcript involving EWSR1-FL11. Juvenile xanthogranuloma (JXG) presented by butter fly like skin patch in the face with foamy histiocytes in upper dermis with few Touton giant cells, extensive systemic involvement of lung and bone marrow. Metastatic ovarian choriocarcinoma with choriocarcinoma syndrome received induction two different lines of chemotherapy and consolidated with autologous stem cell transplant. Seven pediatric rare tumors, with different aspects of challenges in diagnosis and management, despite the absence of formal protocols and rarity of other center experiences.
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In January 2020, the WHO declared the novel coronavirus (2019-nCoV) outbreak as a public health emergency of international concern. Due to the rapid spread of 2019-nCoV, all countries started preventive and precautionary measures to prevent COVID-19 infection spread. These measures limited the population mobility and services provided, which subsequently Impact of on children with cancer and cancer care delivery in the many health centers in Saudi Arabia. We did a cross-sectional study to assess the impact of this outbreak on children with cancer concerning all aspects of life including medical services provided, the specific precautions to prevent spread in cancer patients, mental, psychological effects, and its effect on the quality of life. We collected 204 responses during a survey that assessed the impact on the treatment of cancer children at a tertiary institution during the COVID-19 pandemic. The majority of patients were receiving ongoing chemotherapy for leukemia/lymphoma. The majority of these patients (60.5%) reported a delay in treatment received due to hospital cancellation of appointments due to the pandemic. Although the majority of patients in our cohort complained of delayed treatment, fortunately, none of the delays led to fatalities. In the context of global lockdowns and physical distancing to help flatten the COVID-19 curve, telemedicine has proved fundamental to keeping patients and their healthcare providers connected and safe. Children also faced multiple other difficulties such as psychosocial issues during the COVID-19 pandemic. Our long-term goals are to develop new programs that will enable children with cancer to emerge successfully during a pandemic.