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Objective:To analyze the clinical and laboratory characteristics of acute myeloid leukemia (AML) patients with NPM1 mutation, and to explore the prognostic factors.Methods:A total of 77 AML patients with NPM1 gene mutation admitted to Hebei Yanda Ludaopei Hospital from May 1st 2012 to December 31st 2021 were enrolled in the study, including 34 male and 43 female patients. The median age was 40 (3, 68) years old. Patients were selected and divided into 4 groups according to the morphological FAB classification. There were 29 cases (37.7%) of M1 type, 13 cases (16.9%) of M2 type, 23 cases (29.9%) of M4 type, and 12 cases (15.5%) of M5 type. The clinical characteristics, bone marrow/peripheral blood cell morphology, immunophenotype, cytogenetics, molecular biology and overall survival of different groups were retrospectively analyzed, and the risk factors affecting the prognosis of AML were also explored. Cox multivariate regression was used to analyze the clinical influencing factors of survival and prognosis.Results:The white blood cell counts were highest in M4 and M5 patients and lowest in M2 patients, while no significant difference in the red blood cell, hemoglobin, and platelet counts( P>0.05). Morphologically, there were significant differences in the percentage of blasts and blasts with cup-like nuclei on bone marrow (BM) and peripheral blood (PB). The proportion of blasts in BM and PB was the highest in M1 and the lowest in M2 ( P<0.001). The positive rate of blasts with cup-like nuclei was the highest in M1 and the lowest in M5 of BM ( P<0.001), while the highest in M2 and the lowest in M5 of PB ( P=0.006). The scores of myeloperoxidase and chloroacetate esterase were all the highest in M1 and the lowest in M5 ( P<0.001, 0.001, respectively). In terms of molecular biology, the occurence rate of blasts combined with DNMT3A mutation was the highest in M4 and the lowest in M2 ( P=0.044), while those combined with FLT3-ITD mutation was the highest in M4 and the lowest in M5 ( P=0.002). In immunophenotype, there were significant differences in the expression positivities of seven antigens including HLA-DR, CD56, CD11c, CD15, CD14, CD96 and cMPO ( P<0.05). Multivariate COX regression analysis showed that no recurrence after treatment ( P<0.001), complete remission after treatment ( P=0.015) and transplantation ( P<0.001) were correlated with overall survival (OS). No recurrence after treatment ( P=0.033), transplantation ( P=0.027), no mutation of FLT3-ITD ( P=0.040), and hemoglobin concentration ( P=0.023) were associated with relapse-free survival (RFS). Survival analysis by Kaplan-Meier curve showed that there was no significant difference in survival time between the M1, M2, M4 and M5 groups in OS and RFS. Conclusion:There were significant differences in the white blood count, the percentage of blasts and blasts with cup-like nuclear morphology, cytochemical staining (MPO integration, CE integration and percentage of NAS-DCE), gene mutation (DNMT3A and FLT3-ITD) and immunophenotypes (HLA-DR, CD56, CD11c, CD15, CD14, CD96 and cMPO) between the four groups. The multivariate analysis revealed that no recurrence after treatment and transplantation were independent prognostic factors in NPM1 mut AML patients. On the other hand, FLT3-ITD mutation and hemoglobin concentration were associated with RFS and complete remission after treatment was associated with OS in the entire NPM1 mut cohort.
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Although great progress has been made in the treatment of renal calcium oxalate stones, the incidence and recurrence rate are still high. Functional nanomaterials refer to nanomaterials with specific functions after physical or chemical action.Their role in the treatment of renal calcium oxalate stones has been widely recognized in recent years. Functional nano-materials can be divided into nano-enzymes, nano-drugs and nano-carriers according to their functions. Nano-enzymes and nano-drugs can prevent and treat calcium oxalate kidney calculi by using their physical and chemical properties or drugs. Nano-carriers can treat kidney stones by delivery of the drugs. The purpose of this paper is to describe the application of functional nanomaterials in the prevention and treatment of renal calcium oxalate stones, to summarize the mechanism of inhibiting the formation of renal calcium oxalate stones and the direction of clinical treatment in the future.
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Objective:To investigate the molecular genetic and clinical characteristics of MEF2D-BCL9 fusion gene-positive acute B-cell lymphoblastic leukemia (B-ALL), and to provide the reference for the diagnosis and treatment of the disease.Methods:The medical record and experimental examination data of a 18-year-old female MEF2D-BCL9 fusion gene-positive B-ALL patient were retrospectively analyzed. The clinical manifestations and biological characteristics of MEF2D-BCL9 fusion gene-positive B-ALL were summarized.Results:This 18-year-old female patient was treated in a local hospital in December 2018 and was diagnosed as B-ALL. She achieved complete remission after chemotherapy and recurred at 6 months after the initial onset, and then she was admitted to Hebei Yanda Ludaopei Hospital in the 9 months after the initial onset.MEF2D-BCL9 fusion gene was detected through RNA-sequencing (RNA-seq) and verified by using polymerase chain reaction and Sanger sequencing. Bone marrow cell morphology was similar to mature B cells with vacuoles but without characteristic chromosome karyotype abnormalities. The patient achieved remission after VLD regimen chemotherapy, chimeric antigen receptor T-cell (CAR-T) therapy and bridged to allogeneic hematopoietic stem cell transplantation (allo-HSCT). She has maintained complete remission for 2 years at the last follow-up in February 2022.Conclusions:MEF2D-BCL9 fusion gene-positive B-ALL is characterized with high risk, early relapse and poor prognosis. These patients may benefit from CAR-T and allo-HSCT. It further emphasizes the importance of taking MEF2D-BCL9 fusion gene into the detection or identification by using RNA-seq, particularly for those newly diagnosed B-ALL patients in children and adolescents with specific bone marrow morphology.
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Whether Fanconi anemia (FA) heterozygotes are predisposed to bone marrow failure and hematologic neoplasm is a crucial but unsettled issue in cancer prevention and family consulting. We retrospectively analyzed rare possibly significant variations (PSVs) in the five most obligated FA genes, BRCA2, FANCA, FANCC, FANCD2, and FANCG, in 788 patients with aplastic anemia (AA) and hematologic malignancy. Sixty-eight variants were identified in 66 patients (8.38%). FANCA was the most frequently mutated gene (n = 29), followed by BRCA2 (n = 20). Compared with that of the ExAC East Asian dataset, the overall frequency of rare PSVs was higher in our cohort (P = 0.016). BRCA2 PSVs showed higher frequency in acute lymphocytic leukemia (P = 0.038), and FANCA PSVs were significantly enriched in AA and AML subgroups (P = 0.020; P = 0.008). FA-PSV-positive MDS/AML patients had a higher tumor mutation burden, higher rate of cytogenetic abnormalities, less epigenetic regulation, and fewer spliceosome gene mutations than those of FA-PSV-negative MDS/AML patients (P = 0.024, P = 0.029, P = 0.024, and P = 0.013). The overall PSV enrichment in our cohort suggests that heterozygous mutations of FA genes contribute to hematopoietic failure and leukemogenesis.
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Humans , Anemia, Aplastic/genetics , Epigenesis, Genetic , Fanconi Anemia/genetics , Germ Cells , Hematologic Neoplasms/genetics , Leukemia, Myeloid, Acute/genetics , Retrospective StudiesABSTRACT
Objective:To observe the effect of mirror visual feedback training on upper limb function and muscle tension in children with spastic hemiplegia resulting from cerebral palsy (SHCP).Methods:Seventy-six children aged 2-5 with SHCP were randomly divided into a control group of 33 and a treatment group 34. All were given routine occupational therapy, physical therapy, massage and physical agents. Each therapy session lasted 30 minutes daily, 5 times a week over 3 weeks as a course of treatment. There was a one week interval after each of 6 courses, so the total treatment lasted 6 months. The treatment group was additionally trained with mirror visual feedback with the same schedule. Before, as well as after 3 and 6 months of treatment, each patient′s upper limb motor function, fine motor function and muscle tone were evaluated using the Fugl-Meyer motor function assessment scale (FMA), the Peabody fine motor development scales (PDMS-FM), the modified Ashworth scale (MAS) and integrated electromyograms (iEMGs).Results:There were no significant differences between the two groups before treatment. After both 3 and 6 months significant improvement was observed in both groups′ average FMA score, PDMS-FM total score, grip, and visual motor integration. At both points the treatment group′s averages were significantly better than those of the control group. The average MAS and iEMG results, however, were not significantly different at either time point.Conclusions:For children with spastic hemiplegia caused by cerebral palsy, mirror visual feedback training can effectively improve upper limb functioning, but it cannot reduce their muscle tone.
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Clonal hematopoiesis (CH) refers to the clonal expansion of hematopoietic stem/progenitor cells in some individuals with normal blood indexes. The incidence of CH increases with age, reflecting the decline of the hematopoietic and potential clonal evolution to a certain extent. In recent years, an increasing number of studies have shown that donor CH is an unfavorable factor affecting transplantation, graft-versus-host disease and donor cell leukemia after allogeneic hematopoietic stem cell transplantation. Emphasis on and identification of donor CH can optimize donor selection and help transplant patients benefit more. This article introduces the relevant research progress in combination with the content of the 63rd American Society of Hematology Annual Meeting.
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Resistance or drug-resistant recurrence of targeted tumor therapy is a complex and multi-factorial process, with the final result of tumor clones that can evade treatment or have relative proliferation advantages under treatment pressure being selectively retained. The BCR::ABL1 fusion gene is the primary molecular abnormality of chronic myeloid leukemia (CML), and the development and application of tyrosine kinase inhibitors (TKI) targeting the BCR::ABL1 fusion protein pioneered the era of small molecule targeted therapeutics. Several TKI have been approved for clinical application or in development. Although most CML patients manifest an excellent response to TKI treatment, there are still some patients with poor primary response or relapse with drug resistance. With the increase in the number of patients with long-term maintenance therapy and the sequential use of multiple TKI, the resistance of TKI has become more complicated. This article introduces the research progress of CML molecular resistance mechanisms in recent years and shares the relevant cutting-edge reports at the 63rd American Society of Hematology Annual Meeting in 2021.
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Objective:To investigate the clinical characteristics, diagnosis, treatment and outcome of patients with human herpesvirus 7 (HHV-7) viral encephalitis after allogeneic hematopoietic stem cell transplantation (allo-HSCT).Methods:The clinical manifestations, laboratory characteristics, diagnosis and treatment process and outcome of 3 patients with HHV-7 viral encephalitis after allo-HSCT in Hebei Yanda Lu Daopei Hospital from 2018 to 2020 were retrospectively analyzed, and the related literature was reviewed.Results:The clinical features of 3 patients with HHV-7 viral encephalitis after allo-HSCT included fever, headache, vomiting, apathy, etc., without specific symptoms or signs. The conventional white blood cell count in the cerebrospinal fluid was normal or slightly higher, mainly lymphocytes, and the cerebrospinal fluid protein was normal or slightly higher. The HHV-7 virus DNA in cerebrospinal fluid was positive, and the treatment with ganciclovir or foscarnet was effective. The prognosis was favorable in two mild cases, but one case with cerebral hemorrhage died eventually.Conclusions:HHV-7 viral encephalitis is a rare infection after allo-HSCT, and it can be easily misdiagnosed due to lack of typical symptoms and indications for routine laboratory tests. The detection of HHV-7 DNA in the cerebrospinal fluid can help confirm the diagnosis. Currently, there is no standard treatment programs, but ganciclovir and foscarnet are effective.
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The application of tyrosine kinase inhibitors (TKI) has revolutionarily improved the treatment outcome and survival of patients with chronic myeloid leukemia (CML). The new purpose of the current CML treatment is to achieve a sustained deep molecular biological response to reduce the relapse because of drug resistance and even to achieve treatment-free remission maintenance and cure of the disease. Four kinds of TKI have been approved internationally for the first-line treatment of newly diagnosed chronic-phase CML, and there are constantly new drugs and treatment regimens in development and clinical research. This article introduces the research progress of targeted therapy for CML in combination with the related reports at the 62nd American Society of Hematology Annual Meeting.
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The temperature dependence of relative permittivity and conductivity of
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Animals , Electric Conductivity , Hyperthermia, Induced , Liver , Lung , Swine , TemperatureABSTRACT
The effect of relaxation time in hyperbolic heat transfer model on the temperature field of microwave ablation of atrial fibrillation was investigated. And the results were compared with those calculated by Pennes model. A three-dimensional model of microwave ablation of atrial fibrillation was constructed. The relaxation time (
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Humans , Atrial Fibrillation/surgery , Catheter Ablation , Hot Temperature , Microwaves , Radiofrequency Ablation , TemperatureABSTRACT
OBJECTIVE@#To detect fusion gene with pathological significance in a patient with refractory and relapsed acute B cell lymphoblastic leukemia (B-ALL) and to explore its laboratory and clinical characteristics.@*METHODS@#Transcriptome sequencing was used to detect potential fusion transcripts. Other laboratory results and clinical data of the patient were also analyzed.@*RESULTS@#The patient was found to harbor TCF3 exon 17-ZNF384 exon 7 in-frame fusion transcript. The minimal residual disease (MRD) has remained positive after multiple chemotherapy protocols including CD19-, CD22- targeted chimeric antigen receptor T cells immunotherapy. The patient eventually achieved complete remission and sustained MRD negativity after allogeneic hemopoietic stem cell transplantation (allo-HSCT).@*CONCLUSION@#Transcriptome sequencing can effectively detect potential fusion genes with clinical significance in leukemia. TCF3-ZNF384 positive B-ALL has unique laboratory and clinical characteristics, may not well respond to chemotherapy and immunotherapy, and is more likely to relapse. Timely allo-HSCT treatment may help such patients to achieve long-term disease-free survival. TCF3-ZNF384 positive B-ALL is not uncommon in pediatric patients but has not been effectively identified.
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Child , Humans , B-Lymphocytes , Basic Helix-Loop-Helix Transcription Factors/genetics , Hematopoietic Stem Cell Transplantation , Laboratories , Precursor Cell Lymphoblastic Leukemia-Lymphoma/therapy , Trans-Activators/genetics , TranscriptomeABSTRACT
Structural variation (SV) of the genome is a group of critical genetic abnormalities in hematological tumors. The currently commonly-used cytogenetics and gene testing techniques have significant limitations in the detection of SV. Genome optical mapping technology provides a powerful tool for analyzing SV with ultra-long fragments, high resolution, automation, high throughput and genome-wide range. It is also known as the next-generation cytogenetics (NGC) technology. In recent years, there have been research reports on the use of NGC for the analysis of SV of leukemia genome. The related research progress is now introduced in conjunction with the reports at the 62nd American Society of Hematology Annual Meeting.
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In recent years, the development and widespread application of transcriptome sequencing (RNA-seq) technology has provided powerful tools for direct sequencing and identification of possible fusion transcripts. With the increase in reports of large caese about RNA-seq, the real fusion gene map of hematological malignancies revealed by RNA-seq is becoming clearer. This article introduces the related research progress in conjunction with the reports at the 62nd American Society of Hematology Annual Meeting.
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Disorders of gene expression are closely related to the biological characteristics, treatment response, and prognosis of hematological malignancies. The rapidly-developing transcriptome sequencing and single-cell transcriptome sequencing technologies in recent years provide powerful tools for discovering marker genes and studying gene expression patterns related to disease diagnosis and treatment. This article reviews the related research progress in conjunction with reports at the 62nd American Society of Hematology (ASH) Annual Meeting.
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Objective:To investigate the infection spectrum revealed by metagenomics high-throughput next-generation sequencing (mNGS), and to provide a reference for infection diagnosis after allogeneic hematopoietic stem cell transplantation (allo-HSCT).Methods:A total of 64 patients who developed systemic or local infection symptoms after allo-HSCT in Hebei Yanda Lu Daopei Hospital from January 2018 to November 2018 were enrolled. Gene sequences of pathogenic microorganisms in blood, cerebrospinal fluid and bronchoalveolar fluid specimens were detected by using mNGS. The pathogenic microorganisms or suspected pathogens were determined based on the clinical manifestations of patients.Results:There were 97 samples of mNGS detection for 64 patients who underwent allo-HSCT. The most common gram-positive bacteria were staphylococcus haemolyticus (19 times) and staphylococcus (14 times), and the most common gram-negative bacterium was acinetobacter baumannii (8 times). The most common viruses were cytomegalovirus, EB virus and Torque teno virus (35, 22 and 23 times, respectively), and the most common fungi were malassezia globus (14 times) and candida parapsilosis (8 times). There were 3 mycobacterium tuberculosis complexes detected in 3 patients with acute myeloid leukemia who received allo-HSCT. Mycoplasma orale was detected in one patient's sputum, and none parasite was detected.Conclusion:mNGS can comprehensively reveal the infection spectrum of hematologic diseases after allo-HSCT, especially for pathogenic microorganisms that are rare or difficult to cultivate, and it can effectively help the diagnosis of clinically infectious pathogens.
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With the application of high-throughput gene sequencing, a proportion of somatic gene mutations and clonal hematopoiesis has been found in cases with idiopathic cytopenia of undetermined significance, aplastic anemia, and even in the blood cells of healthy adults. Further researches also put forward concepts such as clonal hematopoiesis of indeterminate significance, clonal cytopenia of undetermined significance, clonal hematopoiesis with oncogenic potential. Studies also showed that clonal hematopoiesis is closely related to inflammation, cardiovascular diseases, solid tumors, and treatment-related bone marrow neoplasms. This article introduces the research progress of clonal hematopoiesis and its relationship with hematological malignancies in combination with the reports at the 61st American Society of Hematology Annual Meeting.
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Objective:To analyze the incidence and mutation characteristics of FLT3 gene mutation and clinical efficacy of tyrosine kinase inhibitor (TKI) in patients with mixed phenotype acute leukemia (MPAL).Methods:A total of 48 patients with MPAL who were admitted to Hebei Yanda Lu Daopei Hospital from June 2015 to February 2018 were retrospectively analyzed. The common mutated 58 genes in hematologic malignancies were detected by using amplicon-targeted next generation sequencing, of which internal tandem duplication (ITD) and point mutation occurred in the hotspot region of exon 14, 15 and 20 in FLT3 gene. Multiplex polymerase chain reaction (PCR) analysis was used to detect 35 gene fusions in hematological neoplams.Results:There were 7 cases of FLT3 mutation in 48 MPAL patients, which were all ITD mutations. The median length of the inserts of FLT3-ITD was 48 bp, and one MPAL patient carried 2 multiple length inserts simultaneously, and the median variant allele frequency (VAF) was 40.5% (7.9%-84.7%). There were no statistically significant differences in clinical and genetic characteristics between FLT3 mutation-positive and FLT3 mutation-negative MPAL patients (both P > 0.05). Among 7 FLT3 mutation-positive MPAL patients, 4 cases were often accompanied with RUNX1 mutation. A total of 4 MPAL patients with FLT3-ITD-positive received sorafenib or sunitinib combined chemotherapy, and 3 of them achieved complete remission. Conclusions:ITD mutation is the main part in the FLT3 mutation of MPAL patients. FLT3-ITD-positive MPAL patients are often accompanied with RUNX1 mutation, which may benefit from targeted therapy with FLT3 kinase inhibitor.
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The new wave of artificial intelligence pushed by deep learning algorithms has dramatically promoted the development of big data analysis technology. On the other hand, advances in life sciences represented by high-throughput genome sequencing have provided massive medical data. Artificial intelligence technology has also provided a powerful tool for hematological malignancy research. This article introduces related research progress in the 61st American Society of Hematology Annual Meeting.
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Objective@#To analyze the incidence and mutation characteristics of FLT3 gene mutation and clinical efficacy of tyrosine kinase inhibitor (TKI) in patients with mixed phenotype acute leukemia (MPAL).@*Methods@#A total of 48 patients with MPAL who were admitted to Hebei Yanda Lu Daopei Hospital from June 2015 to February 2018 were retrospectively analyzed. The common mutated 58 genes in hematologic malignancies were detected by using amplicon-targeted next generation sequencing, of which internal tandem duplication (ITD) and point mutation occurred in the hotspot region of exon 14, 15 and 20 in FLT3 gene. Multiplex polymerase chain reaction (PCR) analysis was used to detect 35 gene fusions in hematological neoplams.@*Results@#There were 7 cases of FLT3 mutation in 48 MPAL patients, which were all ITD mutations. The median length of the inserts of FLT3-ITD was 48 bp, and one MPAL patient carried 2 multiple length inserts simultaneously, and the median variant allele frequency (VAF) was 40.5% (7.9%-84.7%). There were no statistically significant differences in clinical and genetic characteristics between FLT3 mutation-positive and FLT3 mutation-negative MPAL patients (both P > 0.05). Among 7 FLT3 mutation-positive MPAL patients, 4 cases were often accompanied with RUNX1 mutation. A total of 4 MPAL patients with FLT3-ITD-positive received sorafenib or sunitinib combined chemotherapy, and 3 of them achieved complete remission.@*Conclusions@#ITD mutation is the main part in the FLT3 mutation of MPAL patients. FLT3-ITD-positive MPAL patients are often accompanied with RUNX1 mutation, which may benefit from targeted therapy with FLT3 kinase inhibitor.