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1.
Hematol., Transfus. Cell Ther. (Impr.) ; 44(3): 332-335, July-Sept. 2022. tab, graf
Article in English | LILACS | ID: biblio-1405008

ABSTRACT

ABSTRACT Introduction: The myelodysplastic syndrome (MDS) represents a group of hematopoietic neoplasms that is characterized by clonal hematopoiesis, cytopenia and abnormal cellular maturation. Red cell distribution width (RDW) refers to the variation degree of erythrocyte size and it is a reflection of anisocytosis. Higher values have been linked to adverse outcomes, such as increased mortality, vascular events, kidney and liver disease and demonstrated to harbor poor prognosis in solid and hematological malignancies. The RDW value can be used as a contributing parameter for MDS diagnosis, as well as its prognosis. In this study, we essentially aimed to demonstrate the correlation between the RDW and MDS prognostic indexes. Materials and methods: Ninety-four MDS patients at the Aydın Adnan Menderes University Hematology Division were included in the study. The correlations between the RDW and laboratory values (either lactate dehydrogenase, albumin, globulin or ferritin) and the RDW prognostic scoring indexes (IPSS, WPSS, IPSS-R and LR-PSS) were investigated. The PASW for Windows, version 21.0 (SPSS Inc., Chicago, IL, USA), was used for statistical assessment. A p-value below 0.05 was the cut-off for the statistical significance. Results: The mean age of all the patients was 73 ±10 years. Patients were observed for 41.88 ± 25 months. The mean RDW value for all cases was 15.5 ± 2.39. We found a statistically significant difference of survival between RDW values below and above 15.5% (p = 0.016). A significant difference was also observed according to the prognostic scoring indexes (see below). Conclusion: An increase in RDW is probably related to dysplasia in the MDS and this constitutes a possible explanation for the poor outcome. Prognostic indexes might incorporate the RDW as a parameter in the future.


Subject(s)
Myelodysplastic Syndromes , Prognosis , Erythrocytes
2.
Rev. colomb. gastroenterol ; 37(2): 237-241, Jan.-June 2022. tab, graf
Article in English | LILACS | ID: biblio-1394956

ABSTRACT

Abstract Vein thrombosis of unusual sites such as the splanchnic region continues to be not only a diagnostic but also a therapeutic challenge for the clinician due to its manifestation and associated pathologies. Latent JAK2 (Janus kinase 2) positive myeloproliferative neoplasm associated with sticky platelet syndrome is unusual. We present a clinical case of a 38-year-old female patient who presented with sudden onset abdominal pain of a possible vascular origin. Splanchnic thrombosis was diagnosed in latent myeloproliferative neoplasm by identifying the JAK2V617F mutation and sticky platelet syndrome via platelet aggregometry. Off-label anticoagulation with rivaroxaban 20 mg/day was administered. During her outpatient follow-up, she did not suffer any new thrombotic episodes.


Resumen La trombosis venosa de sitios inusuales como la esplácnica continúa siendo un reto no solo diagnóstico sino también terapéutico para el clínico debido a su forma de presentación y las patologías asociadas. La neoplasia mieloproliferativa latente JAK2 (cinasa de Janus 2) positiva asociada con síndrome de plaqueta pegajosa es inusual. Se presenta un caso clínico de una paciente de 38 años de edad que debutó con dolor abdominal de inicio súbito que sugirió un posible origen vascular. Se diagnosticó trombosis esplácnica en relación con neoplasia mieloproliferativa latente por la identificación de la mutación de la JAK2V617F y síndrome de plaqueta pegajosa mediante agregometría plaquetaria. Se administró de manera off-label anticoagulación con rivaroxabán 20 mg/día. Durante su seguimiento ambulatorio no ha presentado nuevos episodios trombóticos.


Subject(s)
Humans , Female , Adult , Blood Platelets , Venous Thrombosis , Neoplasms , Splanchnic Circulation , Syndrome , Myelodysplastic Syndromes
4.
Brasília; CONITEC; fev. 2022.
Non-conventional in Portuguese | LILACS, ColecionaSUS, BRISA | ID: biblio-1377737

ABSTRACT

INTRODUÇÃO: A SMD é uma neoplasia hematológica que inclui um grupo heterogêneo de doenças clonais da células-tronco hematopoiéticas (CTH) caracterizadas por hematopoiese ineficaz, citopenia(s) no sangue periférico e com potencial para evoluir para leucemia mieloide aguda. A presença de citopenia(s) no sangue periférico, definida(s) como hemoglobina < 10g/L, contagem absoluta de neutrófilos < 1,8x109 /L, e/ou plaquetas, < 100x109 /L, associada a alterações displásicas no sangue periférico e medula óssea, na ausência de outras doenças sistêmicas que justifiquem a(s) citopenia(s), são fundamentais para o diagnóstico e classificação desse grupo de doenças. Alfaepoetina é uma eritropoietina humana recombinante, que é quase idêntica ao hormônio eritropoietina endógeno (EPO). A alfaepoetina induz a eritropoiese de uma maneira dependente da dose, mas não afeta a expectativa de vida dos eritrócitos. A presente análise objetiva avaliar a ampliação de uso da alfaepoetina para o tratamento de pacientes adultos com SMD-BR e anemia, que já é utilizada no Brasil para outras indicações. Pergunta: "Para pacientes adultos com SMD-BR, o uso da alfaepoetina quando comparada ao suporte transfusional é seguro, eficaz e custo-efetivo?" Evidências clínicas: Dois ensaios clínicos randomizados (ECR), que utilizaram alfaepoetina subcutânea comparada com grupos placebos, foram selecionados a partir de uma busca bibliográfica conduzida nas bases PubMed, EMBASE e Cochrane Reviews. Uma metanálise foi realizada considerando esses dois estudos, totalizando 123 pacientes incluídos no grupo intervenção e 80 pacientes incluídos no grupo controle. Como resultado, a resposta eritroide alcançada foi de 33,3% no grupo intervenção e 7,5% no grupo controle, levando a um risco relativo (RR) de 4,34 (IC95% 1,91-9,85). Além da resposta eritroide a metanálise avaliou a segurança da alfaepoetina, obtendo valores semelhantes de eventos adversos no grupo intervenção e controle, alcançando RR de 0,96 (IC95% 0,69-1,34). Apenas um estudo avaliou a qualidade de vida, e não houve diferença nesse desfecho entre os grupos em qualquer período. Entretanto, a qualidade de vida na semana 24 foi significativamente diferente entre os pacientes que responderam à alfaepoetina e o grupo placebo (Escore do índice EQ-5D p = 0,034). A qualidade da evidência, segundo o GRADE, foi classificada como moderada para todos os desfechos, com exceção da sobrevida, para qual não se obteve resultados na literatura. Avaliação econômica: Foi realizada uma análise de custo-efetividade por meio de árvore de decisão com cinco anos de horizonte temporal, comparando alfaepoetina com o suporte transfusional. Como resultados, observou-se uma redução de custos de R$ 7.659,52/ano por paciente e uma Razão de Custo-Efetividade Incremental (RCEI) de - R$ 294,38 com alfaepoetina, havendo economia, já que o medicamento é mais eficaz e tem menor custo de tratamento na SMD-BR. Além disso, a análise de sensibilidade determinística univariada, considerando maior preço da tecnologia ou redução no percentual de pacientes em tratamento de sobrecarga de ferro, confirmou que a utilização de alfaepoetina representa menor custo de tratamento. Análise de impacto orçamentário: Nos três cenários apresentados a incorporação da alfaepoetina resulta em economia de recursos de até 51,9%, em relação ao cenário referência (suporte transfusional). Em cinco anos, a incorporação da alfaepoetina pode gerar economia de recursos de até R$ 321 milhões. Na análise de sensibilidade univariada, considerando-se dois cenários apresentados, há economia de recursos entre R$ 32 milhões e R$ 55 milhões, em cinco anos. Monitoramento do Horizonte Tecnológico: Foram identificados dois medicamentos no horizonte tecnológico, tais como luspatercept, aprovado em 2020 no FDA e na EMA para o tratamento de anemia em adultos com SMD de risco muito baixo a intermediário e que falharam aos estimulantes de eritropoiese, mas sem registro na Anvisa para qualquer indicação; e roxadustat, aprovado na EMA em 2021 para o tratamento de anemia em pacientes com insuficiência renal crônica, mas sem registro na Anvisa e FDA para qualquer indicação. Considerações finais: A evidência considerada foi composta por dois ECR de qualidade moderada de acordo com o GRADE, sendo que ambos estudos apresentam resultados favoráveis quanto ao desfecho resposta eritroide e segurança, conforme metanálise condizida. A análise de custo-efetividade encontrou que em relação ao suporte transfusional, o uso da alfaepoetina proporcionaria a redução de custos de R$ 7.659,52/ano por paciente e que a RCEI com o uso da alfaepoetina foi de - R$ 294,38, ou seja, há uma economia com o uso dessa tecnologia para o tratamento da SMD-BR. Na avaliação de impacto orçamentário, a incorporação da alfaepoetina resulta em economia de recursos de até 51,9% (até R$ 321 milhões), em relação ao cenário referência (suporte transfusional). Recomendação preliminar da Conitec: O Plenário da Conitec, em sua 104ª Reunião Ordinária, no dia 08 de dezembro de 2021, deliberou que a matéria fosse disponibilizada em Consulta Pública com recomendação preliminar favorável à ampliação de uso da alfaepoetina para o tratamento de pacientes com Síndrome Mielodisplásica de Baixo Risco com indicação de uso no SUS. Os membros da Conitec consideraram os resultados apresentados (resposta eritroide, qualidade de vida, segurança e avaliação econômica), bem como os argumentos relacionados ao acesso ao medicamento, levantados pelo Plenário, para tomar essa decisão. Consulta pública: A Consulta Pública nº 119 foi realizada entre os dias 28/12/2021 e 17/01/2022. Foram recebidas 45 contribuições, sendo 10 técnico-científicas e 35 sobre experiência ou opinião. Em geral, todas as contribuições concordaram com a recomendação inicial da Conitec, principalmente reforçando a necessidade de ampliação de uso do medicamento. Assim, o Plenário da Conitec entendeu que não houve argumentação suficiente para mudança de entendimento acerca de sua recomendação preliminar. Recomendação final da Conitec: O Plenário da Conitec, em sua 105ª Reunião Ordinária, no dia 09 de fevereiro de 2022, deliberou por maioria simples recomendar a ampliação de uso da alfaepoetina para o tratamento de pacientes com Síndrome Mielodisplásica de Baixo Risco conforme Protocolo Clínico do Ministério da Saúde. Os membros da Conitec consideraram que as evidências científicas sobre o medicamento demonstratam que sua ampliação de uso no SUS seria benéfica aos pacientes com SMD-BR. Além disso, deliberou-se que o presente Relatório de Recomendação seja encaminhado à Anvisa ao final do processo, com o intuito de se esclarecer questões relativas à utilização da alfaepoetina para o tratamento da SMD-BR no Brasil, do ponto de vista regulatório. Por fim, foi assinado o Registro de Deliberação nº 694/2022. Decisão: Ampliar o uso da alfaepoetina para o tratamento de pacientes com síndrome mielodisplásica de baixo risco, conforme Protocolo Clínico do Ministério da Saúde, no âmbito do Sistema Único de Saúde - SUS conforme a Portaria nº 45, publicada no Diário Oficial da União nº 95, seção 1, página 88, em 20 de maio de 2022.


Subject(s)
Humans , Myelodysplastic Syndromes/drug therapy , Erythropoietin/therapeutic use , Unified Health System , Brazil , Cost-Benefit Analysis/economics
6.
Article in Chinese | WPRIM | ID: wpr-939711

ABSTRACT

OBJECTIVE@#To investigate the clinical characteristics and prognosis of hematological malignancies superimposed patients with solid tumors.@*METHODS@#The clinical data of 30 patients with more than two kinds of malignancy (the second is hematological malignancy) from October 2011 to October 2020 in Department of Hematology, Jiangning Hospital Affiliated to Nanjing Medical University were collected and analyzed retrospectively. The overall survival time was used as the prognostic evaluation standard, and the survival of patients were analyzed by KaplanMeier method. Logrank test and Cox regression model were used to carry out univariate and multivariate retrospective analysis on clinical and laboratory parameters of 30 patients.@*RESULTS@#Among 30 cases, 20 were male, 10 were female, the median age of onset of the second tumor was 70 years old. The common types of the secondary hematological malignancies to solid tumors are myelodysplastic syndrome, acute myeloid leukemia, multiple myeloma. Univariate analysis showed that patients' gender, age, type of solid tumors, the onset of interval between two kinds of tumor, chromosome karyotype were not related to do with the patients' overall survival time. Type of hematologic disease, ECOG score were associated with patients' overall survival time, and the multivariate analysis showed that the type of hematologic disease and ECOG score were independent risk factors for patients with poor prognosis.@*CONCLUSION@#Patients superimposed with solid tumors complicated with myelodysplastic syndrome or acute leukemia and ECOG score ≥3 have poor prognosis and shorter overall survival time, which are independent risk factors influencing the prognosis. Bone marrow injury, immune dysfunction and genetic susceptibility after chemoradiotherapy may be the main causes of these diseases.


Subject(s)
Aged , Female , Hematologic Neoplasms/complications , Humans , Leukemia, Myeloid, Acute/complications , Male , Myelodysplastic Syndromes/complications , Prognosis , Retrospective Studies
7.
Article in Chinese | WPRIM | ID: wpr-939692

ABSTRACT

OBJECTIVE@#To screen differentially expressed gene (DEG) related to myelodysplastic syndrome (MDS) based on Gene Expression Omnibus (GEO) database, and explore the core genes and pathogenesis of MDS by analyzing the biological functions and related signaling pathways of DEG.@*METHODS@#The expression profiles of GSE4619, GSE19429, GSE58831 including MDS patients and normal controls were downloaded from GEO database. The gene expression analysis tool (GEO2R) of GEO database was used to screen DEG according to | log FC (fold change) |≥1 and P<0.01. David online database was used to annotate gene ontology function (GO). Metascape online database was used to enrich and analyze differential genes in Kyoto Encyclopedia of Genes and Genomes (KEGG). The protein-protein interaction network (PPI) was constructed by using STRING database. CytoHubba and Mcode plug-ins of Cytoscape were used to analyze the key gene clusters and hub genes. R language was used to diagnose hub genes and draw the ROC curve. GSEA enrichment analysis was performed on GSE19429 according to the expression of LEF1.@*RESULTS@#A total of 74 co-DEG were identified, including 14 up-regulated genes and 60 down regulated genes. GO enrichment analysis indicated that BP of down regulated genes was mainly enriched in the transcription and regulation of RNA polymerase II promoter, negative regulation of cell proliferation, and immune response. CC of down regulated genes was mainly enriched in the nucleus, transcription factor complexes, and adhesion spots. MF was mainly enriched in protein binding, DNA binding, and β-catenin binding. KEGG pathway was enriched in primary immunodeficiency, Hippo signaling pathway, cAMP signaling pathway, transcriptional mis-regulation in cancer and hematopoietic cell lineage. BP of up-regulated genes was mainly enriched in type I interferon signaling pathway and viral response. CC was mainly enriched in cytoplasm. MF was mainly enriched in RNA binding. Ten hub genes and three important gene clusters were screened by STRING database and Cytoscape software. The functions of the three key gene clusters were closely related to immune regulation. ROC analysis showed that the hub genes had a good diagnostic significance for MDS. GSEA analysis indicated that LEF1 may affect the normal function of hematopoietic stem cells by regulating inflammatory reaction, which further revealed the pathogenesis of MDS.@*CONCLUSION@#Bioinformatics can effectively screen the core genes and key signaling pathways of MDS, which provides a new strategy for the diagnosis and treatment of MDS.


Subject(s)
Computational Biology , Gene Expression Profiling , Gene Expression Regulation, Neoplastic , Gene Ontology , Humans , Myelodysplastic Syndromes/genetics
8.
Chinese Journal of Hematology ; (12): 293-299, 2022.
Article in Chinese | WPRIM | ID: wpr-929638

ABSTRACT

Objective: To analyze the influencing factors of iron metabolism assessment in patients with myelodysplastic syndrome. Methods: MRI and/or DECT were used to detect liver and cardiac iron content in 181 patients with MDS, among whom, 41 received regular iron chelation therapy during two examinations. The adjusted ferritin (ASF) , erythropoietin (EPO) , cardiac function, liver transaminase, hepatitis antibody, and peripheral blood T cell polarization were detected and the results of myelofibrosis, splenomegaly, and cyclosporine were collected and comparative analyzed in patients. Results: We observed a positive correlation between liver iron concentration and ASF both in the MRI group and DECT groups (r=0.512 and 0.606, respectively, P<0.001) , only a weak correlation between the heart iron concentration and ASF in the MRI group (r=0.303, P<0.001) , and no significant correlation between cardiac iron concentration and ASF in the DECT group (r=0.231, P=0.053) . Moreover, transfusion dependence in liver and cardiac [MRI group was significantly associated with the concentration of iron in: LIC: (28.370±10.706) mg/g vs (7.593±3.508) mg/g, t=24.30, P<0.001; MIC: 1.81 vs 0.95, z=2.625, P<0.05; DECT group: liver VIC: (4.269±1.258) g/L vs (1.078±0.383) g/L, t=23.14, P<0.001: cardiac VIC: 1.69 vs 0.68, z=3.142, P<0.05]. The concentration of EPO in the severe iron overload group was significantly higher than that in the mild to moderate iron overload group and normal group (P<0.001) . Compared to the low-risk MDS group, the liver iron concentration in patients with MDS with cyclic sideroblasts (MDS-RS) was significantly elevated [DECT group: 3.80 (1.97, 5.51) g/L vs 1.66 (0.67, 2.94) g/L, P=0.004; MRI group: 13.7 (8.1,29.1) mg/g vs 11.6 (7.1,21.1) mg/g, P=0.032]. Factors including age, bone marrow fibrosis, splenomegaly, T cell polarization, use of cyclosporine A, liver aminotransferase, and hepatitis antibody positive had no obvious effect on iron metabolism. Conclusion: There was a positive correlation between liver iron concentration and ASF in patients with MDS, whereas there was no significant correlation between cardiac iron concentration and ASF. Iron metabolism was affected by transfusion dependence, EPO concentration, and RS.


Subject(s)
Ferritins , Humans , Iron , Iron Overload , Liver/metabolism , Myelodysplastic Syndromes/therapy , Primary Myelofibrosis , Retrospective Studies , Splenomegaly
9.
Chinese Journal of Hematology ; (12): 247-254, 2022.
Article in Chinese | WPRIM | ID: wpr-929565

ABSTRACT

Objective: This study aimed to explore the prognostic value of the revised international prognostic scoring system (IPSS-R) and the WHO prognostic scoring system (WPSS) in patients with myelodysplastic syndrome (MDS) undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT). Methods: The clinical data of 184 patients with MDS who received allo-HSCT from July 2016 to June 2019 were retrospectively analyzed. IPSS-R and WPSS were performed at diagnosis and before transplantation. The prognostic values of IPSS-R and WPSS and potential risk factors were explored. Results: With a median follow-up of 21.9 (0.5-47.5) months, the two-year overall survival (OS) and progression-free survival (PFS) rates were (75.1±3.4)% and (71.6±3.6)% , respectively. The two-year cumulative relapse rate and nonrelapse mortality rate were (11.9±0.1)% and (16.5±0.1)% , respectively. There were no significant differences in OS and PFS between the IPSS-R ≤3.5 and >3.5 groups at diagnosis (P=0.409; P=0.724). No significant differences in OS and PFS between the WPSS ≤2 and >2 groups (P=0.426; P=0.726) were observed as well. When the patients were reevaluated before transplantation, the OS and PFS of the IPSS-R ≤3.5 group were significantly better than >3.5 group [OS: (88.6±4.1)% vs (65.8±5.3)% , P=0.003; PFS: (87.6±4.2)% vs (60.5±5.8)% , P=0.002]. However, there were no significant differences in OS and PFS among the WPSS ≤2 and >2 groups (P=0.584; P=0.565). In addition, the OS and PFS of the improved group based on IPSS-R were significantly better than those of the unimproved group before transplantation [OS: (83.8±4.6)% vs (69.3±5.8)% , P=0.027; PFS: (82.8±4.4)% vs. (64.0±7.2)% , P=0.006]. Multivariate analysis indicated that a pretransplant IPSS-R of >3.5 (P=0.021, HR=2.510, 95% CI 1.151-5.476) and TP53 mutation (P=0.047, HR=2.460, 95% CI 1.014-5.971) were independent risk factors for OS, whereas a pretransplant IPSS-R of >3.5 (P=0.017, HR=2.457, 95% CI 1.175-5.141) and pretransplant cytogenetic poor and very poor (P=0.008, HR=2.765, 95% CI 1.305-5.856) were independent risk factors for PFS. Conclusion: A pretransplantation evaluation of IPSS-R could help determine the prognosis of patients with MDS undergoing allo-HSCT. In addition, patients with improved IPSS-R scores before undergoing allo-HSCT had a better prognosis.


Subject(s)
Hematopoietic Stem Cell Transplantation , Humans , Myelodysplastic Syndromes/therapy , Prognosis , Retrospective Studies , Risk Factors
10.
Article in English | WPRIM | ID: wpr-928922

ABSTRACT

DNA hypermethylation is an epigenetic modification that plays a critical role in the oncogenesis of myelodysplastic syndromes (MDS). Aberrant DNA methylation represses the transcription of promotors of tumor suppressor genes, inducing gene silencing. Realgar (α-As4S4) is a traditional medicine used for the treatment of various diseases in the ancient time. Realgar was reported to have efficacy for acute promyelocytic leukemia (APL). It has been demonstrated that realgar could efficiently reduce DNA hypermethylation of MDS. This review discusses the mechanisms of realgar on inhibiting DNA hypermethylation of MDS, as well as the species and metabolisms of arsenic in vivo.


Subject(s)
Arsenicals/therapeutic use , DNA , DNA Methylation/genetics , Humans , Myelodysplastic Syndromes/genetics , Sulfides
11.
Article in Chinese | WPRIM | ID: wpr-928763

ABSTRACT

With the progress of medical technology, cloning hematopoietic was found to be widely exist in normal people. Because of its clinical significance and prognosis is unclear, it is named clonal hematopoiesis of indeterminate potential(CHIP), which has been detected in blood diseases such as myelodysplastic syndrome and lymphoma, and proven to be related to poor prognosis. Recently, CHIP has been also detected in patients with multiple myeloma (MM). In this article, the definition and influencing factors of CHIP, clinical significance, prognosis and treatment in MM were reviewed.


Subject(s)
Clonal Hematopoiesis , Hematopoiesis , Humans , Multiple Myeloma , Mutation , Myelodysplastic Syndromes
12.
Article in Chinese | WPRIM | ID: wpr-928746

ABSTRACT

OBJECTIVE@#To investigate the efficacy and safety of haploidentical hematopoietic stem cell transplantation (haplo-HSCT) in combination of ATG and post-transplant cyclophosphamide (PTCy) -induced immune tolerance after transplantation in treatment of childhood myelodysplastic syndromes(MDS).@*METHODS@#From July 2016 to November 2020, a total of 8 children with MDS receiving the haploidentical allo-HSCT combined with ATG and PTCy-induced immune tolerance after transplantation in our hospital were enrolled, whose clinical data were retrospected and analyzed.@*RESULTS@#Median age at diagnosis of the 8 children (1 male and 7 females) was 6.4 (range, 10 months to 15 years) years old. The median medical history of MDS was 2.7 years (range, 3 months to 8 years). Among the 8 patients, 7 cases were diagnosed with refractory cytopenia of childhood and one with refractory anemia with excess of blasts. The HSC donors were father, mother or brother of patients and HLA matching in 6-9/12 loci were identical. All the donors were healthy and didn't carry the same pathogenic genes as the recipients. The median age of donors was 36.4 (range, 25 to 49) years old. The median mononuclear cell (MNC) number of the graft was 19.8, ranging in (13.2-47.3)×108/kg, and the median CD34+ cell number was 11.8×106/kg, ranging in (5.0-18.3)×106/kg. Graft-versus-host disease prophylactic regimen was started on day 3 and 4 after transplantation, in which cyclophosphamide (50 mg/kg·d) was administered by intravenous infusion. From day 5 after transplantation, low-dose tacrolimus was administered by intravenous infusion and mycophenolate mofetil was administered orally. The median time of neutrophil and platelet engraftment was 12.6 (rang, 11 to 15) days and 13.3 (rang, 11 to 18) days, respectively. All the patients achieved full donor chimerism on neutrophil engraftment after transplantation. The median follow-up time was 1 032 (rang, 747 to 1 536) days. Both overall survival rate and disease-free survival rate were 100%.@*CONCLUSION@#Haplo-HSCT combined with ATG and PTCy-induced immune tolerance after transplantation is a safe and effective treatment for children with MDS.


Subject(s)
Adult , Child , Cyclophosphamide , Female , Graft vs Host Disease/drug therapy , Hematopoietic Stem Cell Transplantation , Humans , Male , Middle Aged , Myelodysplastic Syndromes/drug therapy , Transplantation Conditioning , Treatment Outcome
13.
Article in Chinese | WPRIM | ID: wpr-928745

ABSTRACT

OBJECTIVE@#To identify the key genes and explore mechanisms in the development of myelodysplastic syndrome (MDS) by bioinformatics analysis.@*METHODS@#Two cohorts profile datasets of MDS were downloaded from Gene Expression Omnibus (GEO) database. Differentially expressed gene (DEG) was screened by GEO2R, functional annotation of DEG was gained from GO database, gene ontology (GO) enrichment analysis was performed via Kyoto Encyclopedia of Genes and Genomes (KEGG) database, and key genes were screened by Matthews correlation coefficient (MCC) based on STRING database.@*RESULTS@#There were 112 DEGs identified, including 85 up-regulated genes and 27 down-regulated genes. GO enrichment analysis showed that biological processes were mainly enriched in immune response, etc, cellular component in cell membrane, etc, and molecular function in protein binding, etc. KEGG signaling pathway analysis showed that main gene enrichment pathways were primary immunodeficiency, hematopoietic cell lineage, B cell receptor signaling pathway, Hippo signaling pathway, and asthma. Three significant modules were screened by Cytoscape software MCODE plug-in, while 10 key node genes (CD19, CD79A, CD79B, EBF1, VPREB1, IRF4, BLNK, RAG1, POU2AF1, IRF8) in protein-protein interaction (PPI) network were screened based on STRING database.@*CONCLUSION@#These screened key genes and signaling pathways are helpful to better understand molecular mechanism of MDS, and provide theoretical basis for clinical targeted therapy.


Subject(s)
Computational Biology , Gene Expression , Gene Expression Profiling , Humans , Microarray Analysis , Myelodysplastic Syndromes/genetics , Protein Interaction Maps
14.
Article in Chinese | WPRIM | ID: wpr-928693

ABSTRACT

OBJECTIVE@#To explore the characteristics of infection in patients with myelodysplastic syndromes (MDS), risk factors of serious infection, and their correlation with curative effect.@*METHODS@#The clinical data of 92 newly diagnosed MDS patients with nosocomial infection from January 2016 to June 2020 in our hospital were retrospectively analyzed.@*RESULTS@#A total of 306 courses of treatment were completed in 92 newly diagnosed MDS patients. The infection rate was the highest in the first course of treatment (84.8%, 78/92), and then decreased gradually. The top three infection sites were lung, upper respiratory tract, and gastrointestinal tract. A total of 90 strains of pathogenic bacteria were detected, of which 33.4% (30/90) were gram-negative bacilli, 23.3% (21/90) were gram-positive cocci, 23.3% (21/90) were fungi, and 20.0% (18/90) were viruses. The serious infection rate among 92 patients with MDS was 22.8% (21/92). Multivariate analysis showed that neutrophil deficiency>7 days (OR=10.875, 95%CI: 2.747-43.051, P=0.001) was an independent risk factor for serious infection in MDS patients. Compared with non-severe infection group, the total effective rate of severe infection group was lower (90.9% vs 63.6%, χ2=4.393, P<0.05).@*CONCLUSION@#The infection rate of MDS patients is high in the first course of treatment, and the most common infection site is the lung. Gram-negative bacteria is the most common pathogen. MDS patients with neutrophil deficiency>7 days have a high risk of serious infection and poor efficacy.


Subject(s)
Cross Infection , Gram-Negative Bacteria , Humans , Myelodysplastic Syndromes , Retrospective Studies , Risk Factors
15.
Article in Chinese | WPRIM | ID: wpr-928692

ABSTRACT

OBJECTIVE@#To analyze the clinical characteristics and prognosis of 40 children with myelodysplastic syndrome (MDS), and provide ideas for clinical diagnosis and treatment.@*METHODS@#The clinical characteristics, risk stratification, and different treatment regimens of 40 cases with MDS admitted in Department of Hematology of Children's Hospital of Soochow University from January 1, 2011 to December 31, 2017 was retrospectively analyzed. Kaplan-Meier survival curve were used to estimate 3-year overall survival (OS) rate and event-free survival (EFS) rate.@*RESULTS@#In 40 cases, the ratio of male to female was 1.4∶1.0, male was more than female, and median age was 6.0 years old. Among them, refractory cytopenia (MDS-RCC) was the most common type, and 11 cases were chromosomal abnormalities, 21 cases genetic abnormalities. Fifteen cases accepted hematopoietic stem cell transplantation (HSCT) treatment, while 25 cases did not but drug therapy alone. The 3-year OS rate of the cases who accepted HSCT or not was (72.2±12.2)% and (35.3±10.2)% (P=0.039), 3-year EFS rate was (65.0±12.9)% and (19.2±8.4)% (P=0.012), respectively. Cox regression analysis showed that age < 7 years old (P=0.0333), initial diagnosed platelet < 50×109/L (P=0.007), presence of complex karyotypes and/or gene mutations (P=0.0002), and treatment without HSCT (P=0.016) were the high-risk factors of prognosis. All the children were classified according to IPSS, WPSS and IPSS-R, while analysis result showed that the above three risk assessment had limitations for risk assessment of MDS in children, they could not comprehensively assess the prognosis of children with MDS.@*CONCLUSION@#MDS-RCC in children is more common. Cox multivariate analysis shows that age < 7 years old, initial diagnosed platelet < 50×109/L, presence of complex karyotypes and/or gene mutation, and treatment without HSCT are the high-risk factors of prognosis in children with MDS. HSCT is the most effective treatment to cure children with MDS at present. The current methods such as IPSS-R commonly used in assessment of prognosis in children with MDS show obvious limitation.


Subject(s)
Child , Female , Hematopoietic Stem Cell Transplantation , Humans , Male , Myelodysplastic Syndromes/therapy , Prognosis , Retrospective Studies , Treatment Outcome
16.
Article in Chinese | WPRIM | ID: wpr-928667

ABSTRACT

OBJECTIVE@#To investigate regulatory T cells (Tregs) relative content in peripheral blood and bone marrow of patients with myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) treated with or without decitabine (DAC), analyze the immunomodulatory of Tregs in pathogenesis and remission of MDS and AML, as well as effect of DAC on Tregs.@*METHODS@#From October 2018 to February 2019, 15 patients with MDS and 49 patients with AML (newly diagnosed, treated with DAC or other chemotherapy regimens) were enrolled in this study, and 14 cases with iron deficiency or megaloblastic anemia while without malignant tumor and autoimmune disease as controls. The Tregs relative contents in bone marrow and peripheral blood were analyzed by flow cytometry, meanwhile clinical data of the objects were collected.@*RESULTS@#In peripheral blood and bone marrow of the patients with MDS and AML, the Tregs relative contents at newly diagnosed were higher than those of the control group (P=0.05, P=0.043). The Tregs relative content of AML patients in DAC regimen treatment group was significantly lower than that in the newly diagnosed group and non-DAC chemotherapy group (P<0.05). In DAC regimen treatment group, the Tregs relative contents was significantly lower in remission group than in non-remission group (P<0.05). There was no difference between DAC regimen treatment group and control group in Tregs relative content.@*CONCLUSION@#DAC may increase the body's anti-tumor immunity by consuming Tregs content, enhance the body's immune function to identify and kill tumor cells, thereby promote the patients' reliefs.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols , Bone Marrow , Decitabine/therapeutic use , Humans , Leukemia, Myeloid, Acute/drug therapy , Myelodysplastic Syndromes/drug therapy , T-Lymphocytes, Regulatory , Treatment Outcome
17.
Article in Chinese | WPRIM | ID: wpr-928664

ABSTRACT

OBJECTIVE@#To investigate the genetic and prognostic characteristics of acute myeloid leukemia with myelodysplasia-related changes (AML-MRC) patients.@*METHODS@#There were 230 non-M3 AML patients treated in Ningbo First Hospital enrolled, among which 58 patients were newly diagnosed AML-MRC, the patients were followed up and SPSS 25.0 was used to statistically analyze.@*RESULTS@#There were 49 patients performed genetic testing, 29 patients (59.2%) showed chromosomal abnormalities, including 7q- 8 cases (16.3%), 5q- 6 cases (12.2%), 5 cases (10.2%) of 17p abnormalities, 13 cases (26.5%) of highly abnormal complex karyotypes (CK) (≥5 unrelated chromosomal abnormalities), CK contained chromosomal abnormalities such as +8, 5q-, and 12 cases (24.5%) of monosomal karyotypes (MK). Genetic testing was performed in 37 patients, and 24 (64.9%) patients showed genetic mutations, among which ASXL1 mutation was the most common (8 cases, 21.6%), followed by TET2 mutation in 6 cases (16.2%). Kaplan-Meier analysis showed that AML-MRC patients with high CK (P=0.012), 5q- abnormalities (P=0.038), and TP53 mutations (P=0.008) had poor overall survival.@*CONCLUSION@#AML-MRC has unique genetic characteristics, and high CK, 5q- and TP53 mutations are poor prognostic factors.


Subject(s)
Humans , Karyotype , Karyotyping , Leukemia, Myeloid, Acute/genetics , Myelodysplastic Syndromes , Prognosis
18.
Hematol., Transfus. Cell Ther. (Impr.) ; 43(3): 377-381, July-Sept. 2021. tab, ilus
Article in English | LILACS | ID: biblio-1346260

ABSTRACT

Myelodysplastic syndromes (MDS) are a heterogeneous group of hematological malignancies characterized by dysplasias, ineffective hematopoiesis and risk of acute myeloid leukemia transformation. Approximately 90% of MDS patients present mutations in genes involved in various cell signaling pathways. Specialized DNA polymerases, such as POLN, POLI, POLK, POLQ, POLH, POLL and REV3L, insert a nucleotide opposite replication-blocking DNA lesions in an error-prone manner and, in this way, sometimes can actively promote the generation of mutation. For the best of our knowledge, has not been described the mutations of these genes in MDS. DNA target sequencing CDS regions of the REV3L gene was performed in a 58-year-old man diagnosed as High Risk Myelodysplastic Syndrome. The patient presented very low hemoglobin, increased number of blasts, karyotype:47,XY,+8[6]/47,XY,del(7)(q32),+8[7], no response to hypomethylating therapy (decitabine), all markers of poor prognosis. Target sequencing identified a mutation c.9253-6T>C REV3L (Substitution - intronic) with VAF (variant allele frequency) = 16% considered pathogenic according to Functional Analysis through. Hidden Markov Models (FATHMM). This is the first evidence of REV3L mutation in MDS and, of utmost importance, associated with poor prognosis.


Subject(s)
Humans , Male , Middle Aged , Myelodysplastic Syndromes , Prognosis
20.
Medicina (B.Aires) ; 81(3): 438-451, jun. 2021. graf
Article in Spanish | LILACS | ID: biblio-1346482

ABSTRACT

Resumen Las infecciones fúngicas invasoras (IFI) constituyen una de las principales complicaciones infecciosas en pacientes oncohematológicos y con trasplante de células progenitoras hematopoyéticas (TCPH), ocasionando alta morbimortalidad e incrementando significativamente los costos de atención y la estadía hos pitalaria. La epidemiología de las IFI ha cambiado en las últimas décadas, siendo los hongos filamentosos, particularmente Aspergillus spp., los principales agentes etiológicos. Existen múltiples factores de riesgo para una IFI; pero la neutropenia profunda y prolongada, y la inmunodeficiencia celular severa siguen siendo los más importantes. Por este motivo, la población de mayor riesgo la constituyen los pacientes con leucemias agudas, mielodisplasias y TCPH alogénicos con enfermedad injerto contra huésped (EICH), en tratamiento con corticoides. Numerosos ensayos clínicos aleatorizados y metaanálisis han demostrado que la profilaxis antifúngica primaria (PAF) reduce significativamente la incidencia de IFI, tanto de aquellas causadas por Candida spp. como por Aspergillus spp., la mortalidad relacionada a IFI y la mortalidad global en algunos grupos de pacientes. Asimismo, en enfermos de alto riesgo, en donde se espera una incidencia de IFI elevada, es una estrategia costo-efectiva. Varios antifúngicos han demostrado beneficio clínico y pueden utilizarse como estrategia de PAF en diferentes escenarios, presentando ventajas y desventajas que deben ser tenidas en cuenta al momento de indicar una PAF. Para esto, sociedades científicas nacionales e internacionales, han emitido recomendaciones de indicación de PAF. Se analizan los aspectos relacionados con la eficacia clínica de los diferentes antifúngicos según la población de riesgo, las potenciales desventajas, momento y forma de administración.


Abstract Invasive fungal infections (IFI) are among the main infectious complications in patients with hema tological malignancies and with hematopoietic stem cell transplant (HSCT), causing high morbidity and mortality and significantly increasing the healthcare cost and hospital stay. The epidemiology of IFIs has changed in recent decades, with filamentous fungi, particularly Aspergillus spp., being the main etiological agents. There are multiple risk factors for having an IFI; however, the most important are profound and prolonged neutropenia and severe cellular immunodeficiency. For this reason, the population at greatest risk is made up of patients with acute leukemias, myelodysplasias and allogeneic HSCT with graft-versus-host disease (GVHD) treated with cortico steroids. Numerous randomized clinical trials and meta-analyses have shown that primary antifungal prophylaxis (AFP) significantly reduces the incidence of IFI, particularly those caused by Candida spp. and Aspergillus spp., IFI-related mortality, and overall mortality in some group of patients. Likewise, in high-risk patients, where a high incidence of IFI is expected, it is a cost-effective strategy. Several antifungals have demonstrated clinical benefit. They can be used as a AFP strategy in different settings, presenting advantages and disadvantages that must be taken into account in each case. For this, national and international scientific societies have issued recom mendations for the indication of AFP. Aspects related to the different antifungals' clinical efficacy are analyzed considering the population at risk, the potential disadvantages, timing, and form of administration.


Subject(s)
Humans , Myelodysplastic Syndromes , Hematopoietic Stem Cell Transplantation/adverse effects , Graft vs Host Disease , Neutropenia/drug therapy , Antifungal Agents/therapeutic use
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