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BACKGROUND: Myelodysplastic neoplasms (MDS) are myeloid neoplasms characterized by disordered differentiation of hematopoietic stem cells and a predisposition to acute myeloid leukemia (AML). The underline pathogenesis remains unclear. METHODS: In this study, the trajectory of differentiation and mechanisms of leukemic transformation were explored through bioinformatics analysis of single-cell RNA-Seq data from hematopoietic stem and progenitor cells (HSPCs) in MDS patients. RESULTS: Among the HSPC clusters, the proportion of common myeloid progenitor (CMP) was the main cell cluster in the patients with excess blasts (EB)/ secondary AML. Cell cycle analysis indicated the CMP of MDS patients were in an active proliferative state. The genes involved in the cell proliferation, such as MAML3 and PLCB1, were up-regulated in MDS CMP. Further validation analysis indicated that the expression levels of MAML3 and PLCB1 in patients with MDS-EB were significantly higher than those without EB. Patients with high expression of PLCB1 had a higher risk of transformation to AML. PLCB1 inhibitor can suppress proliferation, induce cell cycle arrest, and activate apoptosis of leukemic cells in vitro. CONCLUSION: This study revealed the transcriptomic change of HSPCs in MDS patients along the pseudotime and indicated that PLCB1 plays a key role in the transformation of MDS into leukemia.
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Leucemia Mieloide Aguda , Síndromes Mielodisplásicas , Humanos , Transcriptoma , Células-Tronco Hematopoéticas/metabolismo , Síndromes Mielodisplásicas/patologia , Leucemia Mieloide Aguda/genética , Perfilação da Expressão GênicaRESUMO
OBJECTIVE: To analyze the clinical characteristics, treatment and prognosis of hemophagocytic lymphohistiocytosis (HLH) patients with Epstein-Barr viremia (EBV). METHODS: A retrospective study was conducted to analyze the clinical data of 80 HLH patients aged ≥ 14 years with EBV-DNA >1 000 copies/ml in peripheral blood from 2008 to 2013. RESULTS: There were EBV-HLH (n = 46), HLH-associated lymphoma (n = 30) and primary HLH (n = 4). Among the relevant laboratory parameters, inter-group statistical differences existed only in alanine transaminase (ALT) and aspartate aminotransferase (AST) (P = 0.021, 0.035). The median follow-up period was 2.0 (0.5-20.0) months. And the 1-month, 3-month, 6-month and 12-month overall survival rates were 58.8%, 37.5%, 29.7% and 19.6% respectively. CONCLUSIONS: HLH patients with EBV have a pernicious clinical course with a poor prognosis. And it makes little sense for distinguishing HLH-associated lymphoma from EBV-HLH through routine laboratory tests.
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Infecções por Vírus Epstein-Barr , Linfo-Histiocitose Hemofagocítica , Viremia , Humanos , Prognóstico , Estudos Retrospectivos , Taxa de SobrevidaRESUMO
Glioblastoma (GBM) remains the most lethal primary brain tumor, characterized by dismal survival rates. Novel molecular targets are urgently required to enhance therapeutic outcomes. A combination of bioinformatics analysis and experimental validation was employed to investigate the role of EGFLAM in GBM. The Chinese Glioma Genome Atlas provided a platform for gene expression profiling, while siRNA-mediated knockdown and overexpression assays in GBM cell lines, alongside in vivo tumorigenesis models, facilitated functional validation. EGFLAM was found to be significantly overexpressed in GBM tissues, correlating with adverse prognostic factors and higher tumor grades, particularly in patients over the age of 41. Functional assays indicated that EGFLAM is vital for maintaining GBM cell proliferation, viability, and invasiveness. Knockdown of EGFLAM expression led to a marked decrease in tumorigenic capabilities. Proteomic interactions involving EGFLAM, such as with NUP205, were implicated in cell cycle regulation, providing insight into its oncogenic mechanism. In vivo studies further demonstrated that silencing EGFLAM expression could inhibit tumor growth, underscoring its therapeutic potential. The study identifies EGFLAM as a pivotal oncogenic factor in GBM, serving as both a prognostic biomarker and a viable therapeutic target. These findings lay the groundwork for future research into EGFLAM-targeted therapies, aiming to improve clinical outcomes for GBM patients.
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Biomarcadores Tumorais , Neoplasias Encefálicas , Proliferação de Células , Glioblastoma , Humanos , Glioblastoma/genética , Glioblastoma/terapia , Glioblastoma/metabolismo , Glioblastoma/patologia , Animais , Linhagem Celular Tumoral , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/terapia , Neoplasias Encefálicas/metabolismo , Prognóstico , Feminino , Masculino , Regulação Neoplásica da Expressão Gênica , Camundongos , Camundongos Nus , Pessoa de Meia-Idade , Adulto , Ensaios Antitumorais Modelo de Xenoenxerto , Terapia de Alvo MolecularRESUMO
To compare the outcomes between peripheral blood stem cell (PBSC)+cord blood and PBSC+bone marrow (BM) grafts in the setting of haploidentical donor (HID) transplantation, 110 patients were enrolled in this retrospective study, including 54 recipients of haplo-PBSC+cord transplants and 56 recipients of haplo-PBSC+BM transplants. Chimerism analyses revealed that by day 30 post-transplantation, 94.3% of surviving patients in the haplo-PBSC+cord group had achieved full haploidentical chimerism and 5.7% had <10% cord chimerism, whereas 100% of surviving patients in the haplo-PBSC+BM group had achieved full donor chimerism. The cumulative incidence of platelet engraftment at 30 days was 92.6% in the haplo-PBSC+cord group versus 89.3% in the haplo-PBSC+BM group (P =.024), that of grade II-IV acute graft-versus-host disease (GVHD) at 100 days was 31.5% versus 48.2% (P =.060), and 1-year relapse was 13.0% versus 25.0% (P =.027), nonrelapse mortality was 9.3% versus 12.5% (P =.76), disease-free survival (DFS) was 77.7% versus 62.5% (P =.028), and overall survival (OS) was 81.4% versus 69.6% (P =.046). Multivariate analysis identified haplo-PBSC+cord transplantation as a protective factor for relapse (hazard ratio [HR], .31; P =.007), DFS (HR, .40; P =.007), and OS (HR, .44; P =.016). Overall, haplo-PBSC+cord transplantation led to faster platelet engraftment, lower relapse, and superior DFS and OS compared with haplo-PBSC+BM transplantation and thus might be a better transplant mode in the setting of HID transplantation.
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Neoplasias Hematológicas , Células-Tronco de Sangue Periférico , Humanos , Medula Óssea/patologia , Células-Tronco de Sangue Periférico/patologia , Estudos Retrospectivos , Sangue Fetal , Transplante de Medula Óssea , Recidiva Local de Neoplasia , Neoplasias Hematológicas/terapiaRESUMO
PURPOSE: Myelofibrosis (MF) may serve as a poor prognostic factor in myelodysplastic syndromes (MDS). This study explored the impact of allogeneic hematopoietic stem cell transplantation (allo-HSCT) on the outcome of MDS patients with MF. PATIENTS AND METHODS: Three hundred and sixteen MDS patients were enrolled in this retrospective study. Based on the degree of MF, we divided the patients into 2 groups: grade 0-1 (MF-0/1) and grade 2-3 (MF-2/3) groups. The clinical features, treatments, and prognosis in MDS patients with MF were analyzed. RESULTS: Forty-three (13.6%) patients were diagnosed as MF-2/3. Complex karyotypes were more common in the MF-2/3 compared to MF-0/1 groups (P = 0.002). The overall response rate (ORR) of cytoreduction was 49.0%, along with 53.3% in the MF-0/1 and 16.7% in MF-2/3 groups (P = 0.017). In total, 141 patients underwent allo-HSCT, including 121 in the MF-0/1 and 20 in MF-2/3 groups. The median time to neutrophil reconstruction was 12 (range: 7-34) and 14 (range: 10-45) days (P = 0.005), and platelet reconstruction was 14 (range: 8-68) and 18 (range: 8-65) days (P = 0.045) in the MF-0/1 and MF-2/3 groups, respectively. However, the cumulative incidence of neutrophil and platelet engraftment achieved at day + 30 was not different between the two groups (P = 0.107, P = 0.303, respectively). Non-relapse mortality, relapse, and acute and chronic graft-versus-host disease were similar between the two groups (all P > 0.05). Among patients with allo-HSCT, the 2-year overall survival (OS) was 68.5% (95% CI: 60.1-76.9%) and 68.4% (95% CI: 47.4-89.4%) in the MF-0/1 and MF-2/3 groups, respectively, (P = 0.636). Among patients without allo-HSCT, the 2-year OS was 49.9% (95% CI: 40.7-59.1%) and 19.2% (95% CI: 0-39.6%) in the MF-0/1 and MF-2/3 groups, respectively, (P = 0.002). In multivariate cox analysis, complex karyotype was an unfavorable factor for relapse (HR, 4.16; P = 0.006), disease-free survival (DFS) (HR, 2.16; P = 0.020), and OS (HR, 2.47; P = 0.009) post-transplantation. CONCLUSION: Patients with MF-2/3 have more complex karyotypes and lower ORR of cytoreduction in MDS. Among patients without allo-HSCT, patients with MF-2/3 have a worse prognosis than those with MF-0/1. However, the adverse impact of MF on prognosis may be overcome by allo-HSCT.
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The objective of this study was to describe the clinical and laboratory characteristics, precipitating factors, treatment, and outcome of macrophage activation syndrome (MAS) complicating systemic lupus erythematosus (SLE). A multicenter case-control study was performed across six tertiary hospitals from 1997 to 2014. A total of 32 patients with SLE-associated MAS were enrolled. Sixty-four age- and sex-matched SLE patients diagnosed in the same period without MAS episodes were selected as controls. The most frequent clinical feature was fever, followed by splenomegaly. Hyperferritinemia, hypoalbuminemia, and hyper-lactate dehydrogenase (LDH)-nemia were among the most common laboratory abnormalities. Compared with pre-MAS visit, patients at the onset of MAS had greater frequencies of renal involvement, liver dysfunction, and cytopenia. Receiver operating characteristic (ROC) analysis identified optimal cutoff values of ferritin (>662.5 ng/mL) and LDH (>359 U/mL) to predict the occurrence of MAS in SLE. SLE flare and infection were the common triggers of MAS in SLE. Abortion and parturition were recorded as well. The overall mortality rate was 12.5%. All patients received corticosteroids. Cyclosporine A, cyclophosphamide, and etoposide were the three most commonly used immunosuppressants. Rituximab was given to one patient. Intravenous immunoglobulin (IVIG) was added for 46.9% patients. MAS is a potentially fatal complication of SLE. Its occurrence is most frequently associated with active SLE disease or infection. The presentation of unexplained fever, cytopenia, or liver dysfunction, with high levels of ferritin and LDH, in patients with SLE should raise the suspicion of MAS. Corticosteroids with immunosuppressants and IVIG may be an appropriate treatment.
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Lúpus Eritematoso Sistêmico/complicações , Síndrome de Ativação Macrofágica/complicações , Adolescente , Adulto , Estudos de Casos e Controles , China , Ciclofosfamida/uso terapêutico , Feminino , Humanos , Imunossupressores/uso terapêutico , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Síndrome de Ativação Macrofágica/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento , Adulto JovemRESUMO
OBJECTIVE: To investigate the outcomes, survival status, and the prognostic factors of Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis (EBV-HLH) patients. METHODS: A retrospective study was carried out to analyze the clinical data of 61 EBV-HLH cases, from January 2008 to July 2014. Prognostic factors were analyzed through COX model (single factor and multiple factors). RESULTS: A total of 246 patients with HLH were diagnosed, among which 102 cases were with EBV infection (including 61 EBV-HLH, 36 lymphoma associated HLH, 5 primary HLH. Among the 61 cases, 40 were male and 21 were female, with a ration of 1.9:1. The median age was 28 years (range, 12-78). 1, 3, 6 and 12-month overall survival rates of 61 EBV-HLH were 65.6%, 47.5%, 32.4%, and 25.0%, respectively. The median follow-up time was 3 (0.5-28) months. 12 patients didn't use etoposide within 4 weeks after diagnosis, while HLH-94 protocol was used in 33 patients and HLH-2004 protocol was used in 16 patients. Response rates of theses three groups were 33.3%, 51.5%, and 43.8%, respectively (P=0.401). There was statistically difference between the group without etoposide and the HLH-94/ HLH-2004 group in the overall survival rate (P=0.033). Serum albumin level (P=0.033) and whether EBV could became negative (P=0.010) were independent predictors for EBV-HLH. CONCLUSION: EBV-HLH patients have severe clinical feature and poor prognosis. Early application of immune chemotherapy based on etoposide can improve survival. Serum albumin level and whether EBV can become negative are independent prognostic factors for survival.
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Infecções por Vírus Epstein-Barr , Herpesvirus Humano 4 , Linfo-Histiocitose Hemofagocítica , Adolescente , Adulto , Idoso , Criança , Etoposídeo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida , Resultado do Tratamento , Adulto JovemRESUMO
Leprosy is an infectious chronic granulomatous disease caused by Mycobacterium leprae. The disease mainly affects the skin, peripheral nerves, mucosa, and viscera. The World Health Organization has reported that most countries with high endemicity have reached the goal of eliminating leprosy (defined as reaching a prevalence of <1 leprosy case per 10 000 population) at the national level, after years of proactive control campaigns. The incidence of leprosy has been decreasing across the globe year by year. However, misdiagnosis happens occasionally due to the complexity of clinical manifestations and lack of physician awareness of this disease. We report a case of lepromatous leprosy complicated by hemophagocytosis misdiagnosed as hemophagocytic lymphohistiocytosis.
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Erros de Diagnóstico , Doenças Hematológicas/diagnóstico , Hanseníase Virchowiana/diagnóstico , Linfo-Histiocitose Hemofagocítica/diagnóstico , Adulto , Dexametasona/uso terapêutico , Doenças Hematológicas/complicações , Doenças Hematológicas/tratamento farmacológico , Humanos , Hanseníase Virchowiana/complicações , Hanseníase Virchowiana/tratamento farmacológico , Levofloxacino/uso terapêutico , Masculino , Resultado do TratamentoRESUMO
OBJECTIVE: To investigate the efficacy of liposomal doxorubicin together with etoposide and high dose methylprednisolone (DEP) as a salvage therapy for adult refractory hemophagocytic lymphohistiocytosis (HLH). METHODS: Total 41 patients with refractory HLH were enrolled in this study. The efficacy of treatment with DEP regimen after 2 and 4 weeks were evaluated according to the United States Midwest Cooperative HLH Group. RESULTS: Of 41 refractory HLH patients, 28 were males and 13 females. The median age was 31(18-62) years old. The overall response rate (ORR) was 78.1%(32/41), including 12 patients (29.3%) achieved complete remission (CR) and 20 (48.8%) achieved partial remission (PR). The underlying disease of HLH were identified in 33 patients, including 1 case of primary HLH (CR), 20 cases of lymphoma associated HLH and 12 cases of EBV associated HLH. There were still 8 cases with unknown underlying disease. The 9 patients who had no response to DEP died within 2 to 4 weeks after salvage therapy. Twenty of the 32 patients who achieved PR or CR survived to undergo subsequent chemotherapy, allogenic hematopoietic stem cell transplantation (allo-HSCT) or splenectomy. CONCLUSION: The single-arm study suggested that DEP regimen appeared to be an effective salvage protocol for adult patients with refractory HLH.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Linfo-Histiocitose Hemofagocítica/tratamento farmacológico , Terapia de Salvação , Adolescente , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Cisplatino/administração & dosagem , Etoposídeo/administração & dosagem , Feminino , Transplante de Células-Tronco Hematopoéticas , Humanos , Masculino , Pessoa de Meia-Idade , Prednisona/administração & dosagem , Indução de Remissão , Adulto JovemRESUMO
OBJECTIVE: To analyze the clinical manifestations, laboratory data, therapy, and prognosis in patients with hemophagocytic lymphohistiocytosis (HLH). METHODS: A retrospective study was carried out in 192 adult patients with HLH between 2003 and 2013. RESULTS: Of the 192 cases, 70 cases were secondary to cancer and 64 cases secondary to infection. According to HLH-2004 criteria, the coincidence rate of indices were: fever (98.96%), high level of serum ferritin (94.27%), increased level of soluble interleukin- 2 receptor(sCD25) (94.79%), decreased or absent activity of NK cells (94.27%), cytopenias (80.73%), splenomegaly (80.21%), emophagocytosis in bone marrow, spleen or lymph nodes (74.48%), hypofibrinogenemia (50.52%), hypertriglyceridemia (37.50%). In addition, 94.27% of patients were presented with liver dysfunction, 96.35% with infections, and 75.52% with coagulopathy. Incidences of central nervous system symptoms and rash were 19.27% and 20.31%, respectively. Among cancer, infection and rheumatic group, there were statistically differences on white blood cells (WBC), platelet (PLT), sCD25, alanine aminotransferase, aspartate aminotransferase, total bilirubin and globulin(GLO) (P<0.05). The differences of WBC, PLT, albumin (ALB), GLO, brain natriuretic peptide, creatinine, urea nitrogen between survival group and death group had statistical significance. CONCLUSION: The secondary HLH occurs from various underlined diseases. Cancer, especially T- cell lymphoma, is the main cause, Secondly, it is EB virus infection. The diagnostic sensitive indicators are Persistent fever, higher level of serum ferritin, low or absent NK-cell activity, and increased sCD25 were the most valuable parameters for diagnosis. Cytopenias were not common in early phase of HLH secondary to rheumatic diseases. WBC, PLT, ALB, GLO could be used as the preliminary parameters for diagnosis. Cardiac insufficiency, renal insufficiency and coagulation dysfunction play important roles in prognosis.