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The conventional dose of recombinant human thrombopoietin (rhTPO) in the treatment of immune thrombocytopenia (ITP) is 300 U/kg per day, but the clinical reaction rate is not satisfactory. Accordingly, we explored the efficacy and safety of increasing rhTPO dose in the treatment of ITP. A retrospective study was conducted to collect the clinical data of 105 ITP patients who were divided into two groups, a low-dose group (15 000 U/day) and a high-dose group (30 000 U/day) according to the dose of rhTPO. The total effective rate of the low-dose group and the high-dose group was 31/44 (70.45%) vs. 56/61 (91.80%) (P = .049), and the average time of using rhTPO in the high-dose group was shorter than that in the low-dose group (7 days vs. 10 days, P = .001). On the 7th and 14th day of treatment, the efficacy of the high-dose group was better than that of the low-dose group [45/61 (73.77%) vs. 17/44 (38.64%), P < .001; 55/60 (91.67%) vs. 30/44 (68.18%), P < .05)]. The incidence of treatment related adverse events in the low-dose group and the high-dose group was 6/44 (13.64%) vs. 6/61 (9.84%) (P > .05), which were mild and transient in nature. In our study, high-dose rhTPO had good efficacy and high safety in the treatment of ITP with the efficacy better than low-dose rhTPO especially at day 7.
What is the context? Immune thrombocytopenia (ITP) is an acquired autoimmune disease characterized by low platelet counts due to increased platelet destruction and impaired platelet production.The therapy direction of ITP involves promoting platelet generation, reducing excessive platelet destruction, immune regulation and so on.Recombinant human thrombopoietin (rhTPO), a promote platelet production drug, has pharmacological action similar to that of endogenous TPO. It can increase platelet count rapidly and effectively and has immunological regulation effect as well.It is found that rhTPO can rapidly and effectively increase platelet count, which has potential clinical application value in emergency situations.What is new? Traditionally, rhTPO has been recommended at 300 U/kg per day. Although it can greatly improve the treatment effect of ITP, the effect is not very satisfactory. In clinical practice, it has been observed that rhTPO dosage is often relatively insufficient and the therapeutic effect is poor. Therefore, we explored the efficacy and safety of increasing rhTPO dose in the treatment of ITP.Within the efficacy and safety of rhTPO 15 000 U/day and 30 000 U/day in the treatment of ITP, our analyses suggest that:The early response rate of the high-dose group was better than that of the low-dose group.In the high-dose group, the effective rate of rhTPO alone or combined with glucocorticoids was more than 90%.Treatment related adverse events occurred at a low rate and remained mild and transient.What is the impact? Comparing with conventional dose rhTPO, high-dose rhTPO may have better efficacy and safety in the treatment of immune thrombocytopenia and shorter administration time.
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Púrpura Trombocitopênica Idiopática , Trombocitopenia , Humanos , Púrpura Trombocitopênica Idiopática/tratamento farmacológico , Trombopoetina/efeitos adversos , Contagem de Plaquetas , Estudos Retrospectivos , Trombocitopenia/tratamento farmacológico , Proteínas Recombinantes/uso terapêuticoRESUMO
PURPOSE: In the present study, we characterized the microbiomes of acute leukemia (AL) patients who achieved complete remission following remission induction chemotherapy (RIC) as outpatients, but who did not receive antimicrobials to treat or prevent febrile neutropenia. METHODS: Saliva and stool samples from 9 patients with acute myeloid leukemia, 11 patients with acute lymphoblastic leukemia, and 5 healthy controls were subjected to 16S ribosomal RNA sequencing at baseline and at 3 months following RIC. Only patients who achieved remission at 3 months post-treatment were included. We excluded anyone who used antimicrobials within 2 months of enrollment or at any time during the study period. RESULTS: At baseline, the relative abundances of species of Prevotella maculosa (P=0.001), Megasphaera micronuciformis (P=0.014), Roseburia inulinivorans (P=0.021), and Bacteroides uniformis (P=0.004) in saliva and Prevotella copri (P=0.002) in the stools of controls were significantly higher than in AL patients. Following RIC, the relative abundances of Eubacterium sp. oral clone DO008 (P=0.012), Leptotrichia sp. oral clone IK040 (P=0.002), Oribacterium sp. oral taxon 108 (P=0.029), Megasphaera micronuciformis (P=0.016), TM7 phylum sp. oral clone DR034 (P<0.001), Roseburia inulinivorans (P=0.034), Actinomyces odontolyticus (P=0.014), Leptotrichia buccalis (P=0.005), and Prevotella melaninogenica (P=0.046) in saliva and Lactobacillus fermentum (P=0.046), Coprococcus catus (P=0.050), butyrate-producing bacterium SS3/4 (P=0.013), and Bacteroides coprocola (P=0.027) in the stools of AL patients were significantly greater than in controls. CONCLUSION: Following RIC, several taxa are changed in stool and salvia samples of AL patients. Our results warrant future large-scale multicenter studies to examine whether the microbiota might have an effect on clinical outcomes of AL patients.
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Antineoplásicos/uso terapêutico , Microbioma Gastrointestinal/efeitos dos fármacos , Quimioterapia de Indução , Leucemia/tratamento farmacológico , Leucemia/microbiologia , Adulto , Idoso , Bactérias/classificação , Bactérias/efeitos dos fármacos , Bactérias/genética , Bactérias/isolamento & purificação , Fezes/microbiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Boca/microbiologia , Filogenia , Adulto JovemRESUMO
BACKGROUND: This meta-analysis was performed to explore the impact of minimal residual disease (MRD) prior to transplantation on the prognosis for patients with acute lymphoblastic leukemia (ALL). METHODS: A systematic search of PubMed, Embase, and the Cochrane Library was conducted for relevant studies from database inception to March 2016. A total of 21 studies were included. RESULTS: Patients with positive MRD prior to allogeneic stem cell transplantation (allo-SCT) had a significantly higher rate of relapse compared with those with negative MRD (HR = 3.26; P < 0.05). Pre-transplantation positive MRD was a significant negative predictor of relapse-free survival (RFS) (HR = 2.53; P < 0.05), event-free survival (EFS) (HR = 4.77; P < 0.05), and overall survival (OS) (HR = 1.98; P < 0.05). However, positive MRD prior to transplantation was not associated with a higher rate of nonrelapse mortality. CONCLUSIONS: Positive MRD before allo-SCT was a predictor of poor prognosis after transplantation in ALL. TRIAL REGISTRATION: Not applicable.
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Transplante de Células-Tronco Hematopoéticas , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Adulto , Criança , Intervalo Livre de Doença , Humanos , Neoplasia Residual , Leucemia-Linfoma Linfoblástico de Células Precursoras/mortalidade , Prognóstico , Viés de Publicação , Recidiva , Transplante HomólogoRESUMO
BACKGROUND: CD83 are closely related to the pathogenesis of immune thrombocytopenia (ITP), but the exact mechanism remains unclear. AIM: To explore the relationship between CD83 and CD4+ T cell subsets and clarify the role of CD83 in the pathogenesis of ITP. METHODS: RT-qPCR and Flow cytometry were used to illustrate CD83 expression. The downregulation and overexpression of DC-CD83 were co-cultured with CD4+ T cells to detect cell proliferation, co-cultured supernatant cytokines and Tregs expression. RESULTS: The results indicate that the ITP patients showed higher expression of CD83 than the healthy controls. The proliferation of CD4+ T cells was inhibited by downregulation of DCs-CD83 but promoted by overexpression of DCs-CD83. siRNA-CD83 inhibited proinflammatory IFN-γ and IL-17 secretion while raising TGF-ß, IL-10 concentrations. Overexpression of DCs-CD83 promoted Tregs expression. CONCLUSION: The Th1/Th2 and Th17/Tregs polarization were reversed via interfering DCs with siRNA-CD83. CD83 plays an important role in ITP pathogenesis, suggesting novel treatment for ITP patients.
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Antígenos CD , Antígeno CD83 , Imunoglobulinas , Glicoproteínas de Membrana , Púrpura Trombocitopênica Idiopática , Humanos , Púrpura Trombocitopênica Idiopática/imunologia , Púrpura Trombocitopênica Idiopática/patologia , Glicoproteínas de Membrana/genética , Glicoproteínas de Membrana/metabolismo , Antígenos CD/metabolismo , Imunoglobulinas/genética , Imunoglobulinas/metabolismo , Feminino , Masculino , Adulto , Pessoa de Meia-Idade , Citocinas/metabolismo , Linfócitos T Reguladores/imunologia , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD4-Positivos/metabolismo , Células Dendríticas/imunologia , Células Dendríticas/metabolismoRESUMO
BACKGROUND: Endothelial cells (ECs) are a critical component of the hematopoietic niche, and the cross-talk between ECs and leukemia was reported recently. This study aimed to determine the genes involved in the proliferation inhibition of endothelial cells in leukemia. METHODS: Human umbilical vein endothelial cells (HUVEC) were cultured alone or co-cultured with K562 cell lines. GeneChip assays were performed to identify the differentially expressed genes. The Celigo, MTT assay, and flow cytometric analysis were used to determine the effect of RNAi DIDO on cell growth and apoptosis. The differently expressed genes were verified by qRT-PCR (quantitative real-time PCR) and western-blot. RESULTS: In K562-HUVEC co-cultured cell lines, 323 down-regulated probes were identified and the extracellular signal-regulated kinase 5 (ERK5) signaling pathway was significantly inhibited. Among the down-regulated genes, the death inducer-obliterator gene (DIDO) is a part of the centrosome protein and may be involved in cell mitosis. As shown in the public data, leukemia patients with lower expression of DIDO showed a better overall survival (OS). The HUVEC cells were infected with shDIDO lentivirus, and reduced expression, inhibited proliferation, and increased apoptosis was observed in shDIDO cells. In addition, the expression of Cyclin-Dependent Kinase 6 (CDK6) and Cyclin D1 (CCND1) genes was inhibited in shDIDO cells. Finally, the public ChIP-seq data were used to analyze the regulators that bind with DIDO, and the H3K4me3 and PolII (RNA polymerase II) signals were found near the Exon1 and exon2 sites of DIDO. CONCLUSION: The knock-down of DIDO will inhibit the proliferation of endothelial cells in the leukemia environment. The expression of DIDO may be regulated by H3K4me3 and the inhibition of DIDO may lead to the down-regulation of CDK6 and CCND1. However, how DIDO interacts with CDK6 and CCND1 requires further study.
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Ciclina D1 , Leucemia , Humanos , Ciclina D1/genética , Quinase 6 Dependente de Ciclina/genética , Proliferação de Células/genética , Células Endoteliais da Veia Umbilical Humana/metabolismoRESUMO
This study aimed to explore role of dendritic cells (DCs) fused with endothelial progenitor cells (EPCs) in inhibiting angiogenesis in acute myeloid leukemia (AML) mice. EPCs were isolated from human AML bone marrow mononuclear cells and fused with DCs, which were then injected back into AML mice. Changes in leukemia cells, micro-vessel density (MVD), early EPC molecular markers vascular endothelial growth factor receptor 2 (VEGFR2/KDR) and CD133 in bone marrow were measured. The results indicated that CD133 and KDR expression in EPCs was significantly higher than in epithelial cells (HUVECs). There were 46.14% ± 8.21% DCs doubly positive for VEGFR2 and CD11c, and it was 8.53% ± 1.27% in co-culture group. Fusion rate of DC/EPCs was 37.61% ± 6.94%, and 35.63% ± 6.09% in DC/ECs group. Growth rate of DC/EPCs was faster than that of EPCs (P<0.05). At 14-20 days after fused cells injection, symptoms gradually decreased. There were a greater number of micro-vessels in bone marrow biopsy sections of AML mice than in normal controls (P<0.05). There was slightly lower MVD in EC/DCs compared with EPC/DCs (P>0.05). Positive expression of CD133 and VEGFR2 in bone marrow biopsies of AML mice was significantly higher than that in control mice (P<0.05). Positive expression of CD133 and VEGFR2 in DC/EC fused cells was significantly lower than that before fusion (P<0.05). In conclusion, DC-EPCs play a certain immunosuppressive effect on angiogenesis in AML mice. Our findings provide experimental data support for the construction of a cell vaccine with anti-angiogenic effect.
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BACKGROUND: Leukemia is a hematological malignancy characterized by the proliferation of early lymphoid precursors that replaces normal hematopoietic cells of the bone marrow. Nakhi (Naxi) ethnic minorities considered to be an area of low incidence. MicroRNAs (miRNAs) are a class of small noncoding RNAs that regulate the expression of other genes in various biological processes. The purpose of this work is to study the molecular mechanism of miRNAs in the leukemia from Naxi. METHODS: Six leukemia patients (case 2 to case 7) and one healthy person (case 1) from Nakhi (Naxi) ethnic minorities were recruited. Total RNA was extracted from these samples and small RNA deep sequencing was performed. RESULTS: A list of miRNAs (1,392 known and candidate 125 novels) expressed in leukocytes were identified, and many differentially regulated targets involved in several cellular pathways, such as cancer, Rap1 signaling pathway, Ras signaling pathway, and endocytosis. Additionally, quantitative real time-polymerase chain reaction (qRT-PCR) results show that hsa-miR-181b-5p, hsa-miR-181a-3p, hsa-miR-181a-5p, and hsa-miR-342-3p has different expression patterns in different cancer cells, hsa-miR-450a-5p, and hsa-miR-1255a were dysregulated in all leukemia cells. CONCLUSIONS: Several abnormal expressed miRNAs in leukemia patients were identified, the correlation of miRNAs dysregulation and leukemia biology demonstrates that specific miRNA can be potential therapeutic target.
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Complicações Hematológicas na Gravidez , Púrpura Trombocitopênica Trombótica , Humanos , Feminino , Gravidez , Púrpura Trombocitopênica Trombótica/tratamento farmacológico , Rituximab/uso terapêutico , Países em Desenvolvimento , Proteína ADAMTS13 , Complicações Hematológicas na Gravidez/tratamento farmacológico , Troca PlasmáticaRESUMO
The current study reports the case of a patient with Philadelphia chromosome-negative (Ph-) non-Hodgkin's lymphoma (NHL) and chronic phase (CP) Philadelphia chromosome-positive (Ph+) chronic myeloid leukemia (CML) that also possessed characteristic enlarged lymph nodes. A lymph node biopsy resulted in the diagnosis of CP-CML, in addition to T-lymphoblastic cell NHL with negative break point cluster/Abelson tyrosine kinase fusion genes in the lymph node of the patient, which was diagnosed as Ph- NHL. A review of the literature was performed in the present study to investigate the genetic differences between Ph- NHL and Ph+ NHL in patients with CML. The median age of patients with NHL and CML was 41 years. The follow-up time of patients with Ph+ NHL was significantly shorter (mean, <6 months) compared to the follow-up time of patients with Ph- NHL (mean, >15 months). Therefore the present study concludes that Ph+ NHL may be more aggressive compared with Ph+ NHL. The present study suggests that additional studies are required to assess the clinical and genetic characteristics of NHL patients with CML.