OBJECTIVE:To illustrate the effect of add-on therapy of Traditional Chinese Medicine(TCM)on the long-term survival of anemic lower-risk myelodysplastic syndromes(LR-MDS)patients.METHODS:In this study,we conducted a re...OBJECTIVE:To illustrate the effect of add-on therapy of Traditional Chinese Medicine(TCM)on the long-term survival of anemic lower-risk myelodysplastic syndromes(LR-MDS)patients.METHODS:In this study,we conducted a retrospective analysis of the data of patients with LR-MDS who were identified from Shuguang Hospital between January 2006 and June 2020.The Kaplan-Meier method was used to calculate overall survival(OS),while the Cox model was employed to analyze prognostic factors of long-term survival.A total of 162 patients who met the inclusion criteria were divided into two groups:the TCM group(n=78)or the non-TCM group(n=84).RESULTS:There were no significant differences in baseline characteristics.The cumulative survival rate of the TCM group was significantly higher than that of the non-TCM group[log-rank P=0.029,hazard ratio(HR)=0.484,95%confidence interval(CI)(0.249,0.942),P<0.05].Patients with longer TCM treatment appeared to have better OS(≥12 months vs<12 months);[HR,0.16695%CI(0.055,0.508),P<0.001].According to the Cox model analysis,the combination of TCM and conventional Western Medicine may be a protective factor affecting the long-term survival of LR-MDS patients[HR=0.509,95%CI,(0.261,0.993),P=0.048].The hematologic improvement erythroid response(HI-E)rate of the TCM group was significantly higher than that of the non-TCM group(69.23%vs 52.38%;P=0.028).However,the duration of HI-E and cases of disease progression after HI-E did not significantly differ from the non-TCM group(P>0.05).CONCLUSIONS:The integration of TCM and Western Medicine has the potential to extend the OS of LR-MDS patients when compared to the use of Western Medicine alone.展开更多
Objective:Allogeneic hematopoietic stem cell transplantation(allo-HSCT)is the only potentially curative method for treating myelodysplastic syndrome(MDS).Post-HSCT measurable residual disease(post-HSCT MRD)is associat...Objective:Allogeneic hematopoietic stem cell transplantation(allo-HSCT)is the only potentially curative method for treating myelodysplastic syndrome(MDS).Post-HSCT measurable residual disease(post-HSCT MRD)is associated with inferior transplant outcomes.In this prospective study,we aimed to investigate the prognostic value of post-HSCT MRD in relapse prediction in MDS.Methods:A total of 166 patients diagnosed with MDS were prospectively enrolled in this study.The KaplanMeier method was used to calculate the survival probabilities.Potential risk factors for outcomes after transplantation were evaluated through univariate and multivariate Cox regression models.Results:For patients with negative and positive post-HSCT MRD,the cumulative incidence of relapse(CIR)and disease-free survival(DFS)at 3 years were 5.9%and 69.6%(P<0.001)and 82.7%and 26.1%(P<0.001),respectively.In the multivariate analysis,post-HSCT MRD(HR=22.801,P<0.001)and Revised International Prognostic Scoring System(IPSS-R)risk stratification(HR=4.346,P=0.003)were independently correlated with relapse.A scoring system for relapse prediction was built based on post-HSCT MRD and IPSS-R stratification.The cumulative incidence of relapse at 3 years was 1.1%,15.8%,and 91.7%for patients with scores of 0,1,and 2,respectively(P<0.001).Conclusions:Our results demonstrated both post-HSCT MRD and IPSS-R scores were independent prognostic factors for OS,DFS,and relapse for MDS patients after allo-HSCT.The risk score system could better predict transplant outcomes and refine the risk stratification than alone in patients with MDS.展开更多
Objective:To explore the difference of lymphocyte subsets in peripheral blood(PB)between aplastic anemia(AA)and hypoplastic myelodysplastic syndrome(hypo-MDS)patients,meanwhile to compare the clinical parameters obtai...Objective:To explore the difference of lymphocyte subsets in peripheral blood(PB)between aplastic anemia(AA)and hypoplastic myelodysplastic syndrome(hypo-MDS)patients,meanwhile to compare the clinical parameters obtained from PB and bone marrow(BM).Methods:The lymphocyte subsets in hypo-MDS(n=25)and.AA(n=33)patients were investigated by flow cytometry.Meanwhile,the differences in PB cell counts,biochemical indicators,BM cell counts and abnormal chromosomes between the two groups were analyzed.Results:The percentage of CD8^(+)T cells in AA group was significantly higher than that in hypo-MDS group(P=0.001),while the percentage of CD4^(+)T cells and the CD4^(+)/CD8^(+)ratio in AA group were obviously lower than those in hypo-MDS group(P=0.015 and 0.001,respectively).Furthermore,the proportion of CD4^(+)and CD8^(+)activated T(TA)cells,and memory Tregs in AA group was distinctly lower than those in hypo-MDS group(P=0.043,0.015 and 0.024,respectively).Nevertheless,the percentage of CD8^(+)naive T(TN)cells in AA patients was remarkably higher(P=0.044).And hypo-MDS patients had declined lymphocyte counts(P=0.025),increased levels of total bilirubin(TBil),lactate dehydrogenase(LDH),vitamin B12 and proportion of BM blasts than AA patients(P=0.019,0.023,0.027 and.0.045,respectively).Conclusion:In this study it was confirmed that the percentages of CD4^(+)and CD8^(+)TA cells,memory Tregs and CD8^(+)TN cells were significantly different between AA and hypo-MDS patients,which provide an essential basis for the identification of these two diseases.展开更多
The myelodysplastic/myeloproliferative neoplasms(MDS/MPNs) are a unique group of hematologic malignancies characterized by concomitant myelodysplastic and myeloproliferative features. According to the 2008 WHO classif...The myelodysplastic/myeloproliferative neoplasms(MDS/MPNs) are a unique group of hematologic malignancies characterized by concomitant myelodysplastic and myeloproliferative features. According to the 2008 WHO classification, the category includes atypical chronic myeloid leukemia(a CML), chronic myelomonocytic leukemia(CMML), juvenile myelomonocytic leukemia(JMML), MDS/MPN-unclassifiable(MDS/MPN-U), and the provisional entity refractory anemia with ring sideroblasts and thrombocytosis(RARS-T). Although diagnosis currently remains based on clinicopathologic features, the incorporation of nextgeneration platforms has allowed for the recent molecular characterization of these diseases which has revealed unique and complex mutational profiles that support their distinct biology and is anticipated to soon play an integral role in diagnosis,prognostication, and treatment. Future goals of research should include the development of disease-modifying therapies, and further genetic understanding of the category will likely form the foundation of these efforts.展开更多
OBJECTIVE:To explore the relationship between the efficacy of realgar for the treatment of myelodysplastic syndromes with multilineage dysplasia(MDS-MLD)and arsenic concentration in the peripheral blood of patients.ME...OBJECTIVE:To explore the relationship between the efficacy of realgar for the treatment of myelodysplastic syndromes with multilineage dysplasia(MDS-MLD)and arsenic concentration in the peripheral blood of patients.METHODS:In this prospective study,a total of 50 MDS-MLD patients were treated with traditional Chinese drugs containing realgar for 3 months in Xiyuan Hospital from March 2018 to January 2019.Routine blood examination as well as liver and kidney function were monitored before and after treatment.The concentration of arsenic in the peripheral blood was measured using an atomic fluorescence spectrometer after treatment.The correlation between clinical effect and arsenic concentration was analyzed by Spearman’s method.RESULTS:The treatment response rate was 54%.Two patients(4%)achieved complete remission,50%(25 of 50)showed hematologic improvement,and 23 patients had stable disease(23%).No disease progression was observed.Arsenic concentration in the peripheral blood ranged from 14.60 to 85.96μg/L.Clinical efficacy was positively correlated with arsenic concentration(P<0.05).The incidence of mild adverse reactions was 16%.CONCLUSION:A relatively high concentration of arsenic in the peripheral blood may improve the clinical efficacy of realgar in MDS-MLD patients.展开更多
Myelodysplastic syndromes have increased in frequency and incidence in the American population, but patient prognosis has not significantly improved over the last decade. Such improvements could be realized if biomark...Myelodysplastic syndromes have increased in frequency and incidence in the American population, but patient prognosis has not significantly improved over the last decade. Such improvements could be realized if biomarkers for accurate diagnosis and prognostic stratification were successfully identified. In this study, we propose a method that associates two state-of-the-art array technologies-single nucleotide polymorphism (SNP) array and gene expression array-with gene motifs considered transcription factor -binding sites (TFBS). We are particularly interested in SNP-containing motifs introduced by genetic variation and mutation as TFBS. The potential regulation of SNP-containing motifs affects only when certain mutations occur. These motifs can be identified from a group of co-expressed genes with copy number variation. Then, we used a sliding window to identify motif candidates near SNPs on gene sequences. The candidates were filtered by coarse thresholding and fine statistical testing. Using the regression-based LARS-EN algorithm and a level-wise sequence combination procedure, we identified 28 SNP-containing motifs as candidate TFBS. We confirmed 21 of the 28 motifs with ChIP-chip fragments in the TRANSFAC database. Another six motifs were validated by TRANSFAC via searching binding fragments on coregulated genes. The identified motifs and their location genes can be considered potential biomarkers for myelodysplastic syndromes. Thus, our proposed method, a novel strategy for associating two data categories, is capable of integrating information from different sources to identify reliable candidate regulatory SNP-containing motifs introduced by genetic variation and mutation.展开更多
AIM To evaluate factors associated with Clostridium difficile infection(CDI)and outcomes of CDI in the myelodysplastic syndrome(MDS)and acute myeloid leukemia(AML)population.METHODS After IRB approval,all MDS/AML pati...AIM To evaluate factors associated with Clostridium difficile infection(CDI)and outcomes of CDI in the myelodysplastic syndrome(MDS)and acute myeloid leukemia(AML)population.METHODS After IRB approval,all MDS/AML patients hospitalized at the University of Maryland Greenebaum Comprehensive Cancer Center between August 2011 and December 2013 were identified.Medical charts were reviewed for demographics,clinical information,development of CDI,complications of CDI,and mortality.Patients with CDI,defined as having a positive stool PCR done for clinical suspicion of CDI,were compared to those without CDI in order to identify predictors of disease.A t-test was used for comparison of continuous variables and chisquare or Fisher's exact tests were used for categorical variables,as appropriate.RESULTS Two hundred and twenty-three patients(60.1%male,mean age 61.3 years,13%MDS,87%AML)had 594 unique hospitalizations during the study period.Thirtyfour patients(15.2%)were diagnosed with CDI.Factors significantly associated with CDI included lower albumin at time of hospitalization(P<0.0001),prior diagnosis of CDI(P<0.0001),receipt of cytarabine-based chemotherapy(P=0.015),total days of neutropenia(P=0.014),and total days of hospitalization(P=0.005).Gender(P=0.10),age(P=0.77),proton-pump inhibitor use(P=0.73),receipt of antibiotics(P=0.66),and receipt of DNA hypomethylating agent-based chemotherapy(P=0.92)were not significantly associated with CDI.CONCLUSION CDI is common in the MDS/AML population.Factors significantly associated with CDI in this population include low albumin,prior CDI,use of cytarabine-based chemotherapy,and prolonged neutropenia.In this study,we have identified a subset of patients in which prophylaxis studies could be targeted.展开更多
Behet's disease is characterized by recurrent oral ulcers, genital ulcers, uveitis and skin lesions. Myelodysplastic syndrome (MDS) is characterized by problems due to ineffective hematopoiesis. Several studies ha...Behet's disease is characterized by recurrent oral ulcers, genital ulcers, uveitis and skin lesions. Myelodysplastic syndrome (MDS) is characterized by problems due to ineffective hematopoiesis. Several studies have identified a relationship between MDS and Behet's disease, especially intestinal Behet's disease. Trisomy 8 seems to play an important role in these disorders as well. The present case was a 24-year-old woman who had a huge tonsil ulcer with initial symptoms of odynophagia and intermittent fever. We also noted folliculitis on her upper back. Five days later, she began to experience diarrhea and abdominal pain. Abdominal computed tomography and subsequent surgery revealed ileum perforation and enterocolitis with multiple ulcers. Later, she was admitted again for a vulvar suppurative ulcer and suspicious Bartholin's cyst infection. The patient's clinical presentations met the criteria for Behet's disease. Six months after the bowel perforation event, we noted the development of pancytopenia in a routine laboratory examination. All the examinations led to the diagnosis of MDS with trisomy 8. The most unusual finding was that multiple large vessel thrombi developed during follow-up. Previous studies have suggested that trisomy 8 in MDS leads to concurrent intestinal Behet's disease. Moreover, the inflammatory and immune genes related to thrombus formation are overexpressed in cases of MDS with trisomy 8. Trisomy 8 must play a role in thrombosis. Further studies are needed to help clarify the pathophysiology and pathogenesis of these disorders.展开更多
BACKGROUND Ankylosing spondylitis(AS)is an autoimmune disease characterized by sacroiliitis and spondylitis,with a few hematological abnormalities.Myelodysplastic syndromes(MDS)are a heterogeneous group of hematopoiet...BACKGROUND Ankylosing spondylitis(AS)is an autoimmune disease characterized by sacroiliitis and spondylitis,with a few hematological abnormalities.Myelodysplastic syndromes(MDS)are a heterogeneous group of hematopoietic stem cell disorders with frequent autoimmune phenomena.The relationship between AS and MDS remains unknown.CASE SUMMARY We describe a rare case of concurrent AS and MDS.An 18-year-old man with low back pain and anemia was diagnosed with AS;however,the cause of anemia could not be determined by the first bone marrow examination.He recovered from anemia and the symptoms of AS resolved after treatment with etanercept,glucocorticoid,and blood transfusion,but he developed pancytopenia with an increased myeloblast count(from 2.5%to 9%).Chromosome analysis revealed del(7q)and trisomy 8.Refractory anemia with excess of blasts-1(RAEB-1)/MDS was confirmed by repeating the bone marrow examination.He became blood transfusion-dependent and received decitabine-based chemotherapy but eventually died.CONCLUSION We suspect that AS may be an early autoimmune phenomenon related to MDS.However,a condition of coexistence cannot be excluded.展开更多
Distinguishing between aplastic anemia(AA)and hypoblastic myelodysplastic syndrome(hMDS)with a low percentage of bone marrow(BM)blasts(<5%)can be difficult due to the overlap in clonality and a spectrum of genetic ...Distinguishing between aplastic anemia(AA)and hypoblastic myelodysplastic syndrome(hMDS)with a low percentage of bone marrow(BM)blasts(<5%)can be difficult due to the overlap in clonality and a spectrum of genetic alternations between the two subtypes of diseases.However,due to recent advances in DNA sequencing technology,both spectnim and frequency of mutations can be accurately determined and monitored by next-generation sequencing(NGS)at initial diagnosis and during immunosuppressive therapy(1ST)in patients with AA or hMDS.This improvement in acquiring a patient's genetic status and clonal evolution can provide more proper,precise,and on-time information to guide disease management,which is especially helpful in the absence of traditional morphologic/cytogenetic evidence.展开更多
Objective To investigate the expression of TET2 mRNA and protein in the bone marrow mononuclear cells （BMMNC） of patients with myelodysplastic syndrome （MDS） and its clinical significance. Methods The expression o...Objective To investigate the expression of TET2 mRNA and protein in the bone marrow mononuclear cells （BMMNC） of patients with myelodysplastic syndrome （MDS） and its clinical significance. Methods The expression of TET2 mRNA and protein in bone marrow mononuclear cells （BMMNC） of 32 patients with MDS and 20 healthy donors was examined by qPCR and Western blot. Results The expression of TET2 mRNA in BMMNC was down-regulated in MDS patients compared with the donor group [（0.41±0.28）% vs. （1.07±0.56）%] （P〈0.001）. Compared with lower expression group （TET2〈0.4） [（6.53±6.17）%], patients with higher expression of TET2 ≥0.4） presented significantly lower proportion of bone marrow blasts [（1.21±1.56）%1 （P〈0.05）. The expression of TET2 mRNA in BMMNC of MDS patients was inversely correlated with malignant clone burden （t=--0.398, P〈0.05） and IPSS r=-0.412, P〈0.05）. The expression of TET2 protein was down-regulated in MDS patients compared with that in the donor group. Conclusions The mRNA and protein expression of TET2 in BMMNC of MDS patients is decreased, which might be useful as an important parameter for the evaluation of MDS clone burden.展开更多
BACKGROUND Patients with trisomy 8 consistently present with myeloid neoplasms and/or auto-inflammatory syndrome.A possible link between myelodysplastic syndromes(MDS)with trisomy 8(+8-MDS)and inflammatory disorders i...BACKGROUND Patients with trisomy 8 consistently present with myeloid neoplasms and/or auto-inflammatory syndrome.A possible link between myelodysplastic syndromes(MDS)with trisomy 8(+8-MDS)and inflammatory disorders is well recognized,several cases having been reported.However,inflammatory disorders in patients without MDS have been largely overlooked.Generally,Behçet's disease is the most common type in+8-MDS.However,inflammatory disorders with pulmonary involvement are less frequent,and no effective treatment has been established.CASE SUMMARY A 27-year-old man with recurrent fever,fatigue for>2 mo,and unconsciousness for 1 day was admitted to our emergency department with a provisional diagnosis of severe pneumonia.Vancomycin and imipenem were administered and sputum collected for metagenomic next-generation sequencing.Epstein–Barr virus and Mycobacterium kansasii were detected.Additionally,chromosomal analysis showed duplications on chromosome 8.Two days later,repeat metagenomic next-generation sequencing was performed with blood culture.Cordyceps portugal,M.kansasii,and Candida portugal were detected,and duplications on chromosome 8 confirmed.Suspecting hematological disease,we aspirated a bone marrow sample from the iliac spine,examination of which showed evidence of infection.We added fluconazole as further antibiotic therapy.Seven days later,the patient’s condition had not improved,prompting addition of methylprednisolone as an anti-inflammatory agent.Fortunately,this treatment was effective and the patient eventually recovered.CONCLUSION Severe inflammatory disorders with pulmonary involvement can occur in patients with trisomy 8.Methylprednisolone may be an effective treatment.展开更多
Objective:Although the effect of decitabine on myelodysplastic syndrome(MDS)has been demonstrated,merely a proportion of patients respond to therapy,and no well-recognized predictors have been identified.This study wa...Objective:Although the effect of decitabine on myelodysplastic syndrome(MDS)has been demonstrated,merely a proportion of patients respond to therapy,and no well-recognized predictors have been identified.This study was conducted to investigate the effectiveness of decitabine in real-world clinical practice,and determine the predictive factors of response and overall survival(OS)in MDS patients.展开更多
Objective To investigate the role of the burden of abnormal hematopoietic clone in the development of myelodysplastic syndromes (MDS). Methods The ratio of the bone marrow cells with abnormal chromosomes to the total ...Objective To investigate the role of the burden of abnormal hematopoietic clone in the development of myelodysplastic syndromes (MDS). Methods The ratio of the bone marrow cells with abnormal chromosomes to the total counted bone marrow cells was regarded as the index of MDS clone burden. The disease severity related parameters including white blood cell count, hemoglobin, platelet count, lactate dehydrogenase level, bone marrow blast, myeloid differentiation index, micromegakaryocyte, transfusion, interleukin-2, tumor necrosis factor (TNF), CD4^+ and CD8^+ T cells of MDS patients were assayed, and the correlations between those parameters and MDS clone burden were also analyzed. Results The clone burden of MDS patients was 67.4%±36.2%. MDS clone burden positively correlated with bone marrow blasts (r = 0.483, P<0.05), negatively with hemoglobin level (r=-0.445, P<0.05). The number of blasts, hemoglobin, and erythrocytes in high clone burden (>50%) and low clone burden (≤50%) groups were 7.78%±5.51% and 3.45%±3.34%, 56.06±14.28 g/L and 76.40±24.44 g/L, (1.82±0.48)×10~ 12 /L and (2.32±0.66)×10~ 12 /L, respectively (all P<0.05). CD4^+ T lymphocytes of MDS patients and normal controls were (0.274±0.719)×10~ 9 /L and (0.455±0.206)×10~ 9 /L, respectively (P<0.05). CD8^+ T lymphocytes of MDS patients and normal controls were (0.240±0.150)×10~ 9 /L and (0.305±0.145)×10~ 9 /L, respectively. The serum level of interleukin-2 of MDS patients (6.29±3.58 ng/mL) was significantly higher than normal control (3.11±1.40 ng/mL, P<0.05). The serum level of TNF of MDS patients and normal control group were 2.42±1.79 ng/mL and 1.68±0.69 ng/mL, respectively. The ratio of CD4 to CD8 was higher in high clone burden MDS patients (1.90±0.52) than that in low clone burden patients (0.97±0.44, P<0.05). Conclusion The quantitive clonal karyotype abnormalities and deficient T cell immunity are important parameters for evaluating MDS severity and predicting its progression.展开更多
Background:Myelodysplastic syndrome(MDS)is a group of disorders involving he-mopoietic dysfunction leading to leukemia.Although recently progress has been made in identifying underlying genetic mutations,many question...Background:Myelodysplastic syndrome(MDS)is a group of disorders involving he-mopoietic dysfunction leading to leukemia.Although recently progress has been made in identifying underlying genetic mutations,many questions still remain.Animal models of MDS have been produced by introduction of specific mutations.However,there is no spontaneous mouse model of MDS,and an animal model to simulate natu-ral MDS pathogenesis is urgently needed.Methods:In characterizing the genetically diverse mouse strains of the Collaborative Cross(CC)we observed that one,designated JUN,had abnormal hematological traits.This strain was thus further analyzed for phenotypic and pathological iden-tification,comparing the changes in each cell population in peripheral blood and in bone marrow.Results:In a specific-pathogen free environment,mice of the JUN strain are rela-tively thin,with healthy appearance.However,in a conventional environment,they become lethargic,develop wrinkled yellow hair,have loose and light stools,and are prone to infections.We found that the mice were cytopenic,which was due to abnor-mal differentiation of multipotent bone marrow progenitor cells.These are common characteristics of MDS.Conclusions:A mouse strain,JUN,was found displaying spontaneous myelodysplas-tic syndrome.This strain has the advantage over existing models in that it develops MDS spontaneously and is more similar to human MDS than genetically modified mouse models.JUN mice will be an important tool for pathogenesis research of MDS and for evaluation of new drugs and treatments.展开更多
Objective This study aims to investigate the expression of delta-like 1 （DLK1） gene in the bone marrow cells of patients with myelodysplastic syndromes （MDS） and to explore its molecular characteristics for the ea...Objective This study aims to investigate the expression of delta-like 1 （DLK1） gene in the bone marrow cells of patients with myelodysplastic syndromes （MDS） and to explore its molecular characteristics for the early diagnosis of MDS. Methods The expression of DLK1 mRNA in the bone marrow cells of cases with MDS, acute myeloid leukemia （AML）, and normal control groups were measured by real-time polymerase chain reaction and were analyzed for clinical significance. Results Significantly higher expression of DLK1 mRNA was observed in the bone marrow cells of MDS patients （0.7342±0.3652） compared with the normal control group （0.4801±0.1759） （P〈0.05）. The expression of DLK1 mRNA had a positive correlation with the proportion of bone marrow blasts （r=0.467, P〈0.05）. Moreover, DLK1 mRNA expression was significantly increased as MDS progressed （P〈0.05）. Patients with abnormal karyotypes exhibited significantly higher expression of DLK1 mRNA （0.9007±0.4334） than those with normal karyotypes （0.6411±0.2630） （P〈0.05）. Subsequently, patients with highly expressed DLK1 （≥0.8） presented significantly higher malignant clone burden （0.4134±0.3999） than those with lower DLK1 expression （〈0.8）,（0.1517±0.3109）, （P〈0.05）. Conclusions The DLK1 gene was highly expressed in MDS patients, and was increased as MDS progressed. The expression of DLK1 mRNA was positively correlated with the proportion of the bone marrow blasts. A high expression of DLK1 gene suggested a higher malignant clone burden of MDS.展开更多
BACKGROUND Myelodysplastic syndrome(MDS)is a hematological neoplasm,and an increase in myeloblasts is representative of leukemic hematopoiesis in advanced MDS.Lowrisk MDS usually exhibits deranged autoimmunity resembl...BACKGROUND Myelodysplastic syndrome(MDS)is a hematological neoplasm,and an increase in myeloblasts is representative of leukemic hematopoiesis in advanced MDS.Lowrisk MDS usually exhibits deranged autoimmunity resembling that of aplastic anemia(AA),whereas advanced MDS is characterized by a phenotype of immune exhaustion.MDS can be normo/hyperplastic or hypoplastic.Generally,bone marrow cellularity and myeloblasts increase with disease progression.Transformation from advanced MDS to AA-like syndrome with leukemic cell regression has not previously been reported.CASE SUMMARY A middle-aged Chinese woman had a 4-year history of leukocytopenia.Six months prior to admission,the patient developed gradually worsening fatigue and performance status.The leukocytopenia further progressed.She was diagnosed with MDS with excess blasts-2 based on increased bone marrow cellularity and an increased percentage of myeloblasts on marrow and blood smears,an increased percentage of cluster of differentiation(CD)34+CD33+progenitors in immunotyping analysis,a normal karyotype in cytogenetic analysis,and the identification of somatic mutations in CBL,KMT2D and NF1 in molecular analysis.Initially,neutropenia was the predominant hematological abnormality,with mild anemia and thrombocytosis,and the degree of fatigue was far more severe than the degree of anemia.In the following months,the patient experienced several febrile episodes.Intravenous antibiotic treatments were able to control the febrile episodes,but the elevated inflammatory indices persisted.The hematological parameters dramatically fluctuated with the waxing and waning of the inflammatory episodes.With recurrent flares of the inflammatory condition,agranulocytosis and severe anemia developed,with mild thrombocytopenia.During the patient’s hospitalization,computed tomography(CT)scans revealed the presence of extensive inflammatory lesions involving the lungs,mediastinum,pleura,gastrointestinal tract,peritoneum and urinary tract,with imaging features suggestive of the reactivation of disseminated tuberculosis.Reevaluation of the bone marrow smears revealed that the cellularity became hypoplastic,and the leukemic cells regressed,suggesting that both normal and leukemic hematopoiesis had been heavily suppressed.Immunological analysis of the bone marrow samples revealed a decreased percentage of CD34+cells and an immunological signature resembling that of severe AA(SAA),confirming the regression of the leukemic cells by autoimmune-mediated attacks.The patient demonstrated resistance to multiple drugs,including antituberculotics,recombinant human granulocyte colony-stimulating factor,broad-spectrum antibiotics,voriconazole,ganciclovir,immune suppressants,eltrombopag and intravenous immunoglobulin,which further worsened the hematological injury and patient’s performance status.The patient eventually died of overwhelming infection and multidrug resistance.CONCLUSION Advanced MDS can transform to aplastic cytopenia with leukemic cell regression and an immunological signature of SAA during inflammatory flare-ups.展开更多
OBJECTIVE: To evaluated the benefits of oral administration of arsenic-containing Qinghuang Powder(QHP)compared with decitabine for patients with high/very-high(H/VH) risk myelodysplastic syndrome(MDS) according to th...OBJECTIVE: To evaluated the benefits of oral administration of arsenic-containing Qinghuang Powder(QHP)compared with decitabine for patients with high/very-high(H/VH) risk myelodysplastic syndrome(MDS) according to the Revised International Prognostic Score System. METHODS: The OS(mOS) rate, annual OS rate and progression to acute myeloid leukemia(AML) in patients with H/VH MDS treated with QHP(QHP group, n = 27) and decitabine(decitabine group, n = 20) were retrospectively analyzed. The effects of prognostic factors of age, proportion of bone marrow blast,peripheral blood cell count, karyotype and Charlson Comorbidity Index(CCI) on OS were further analyzed. RESULTS: The m OS rate of QHP group(29 months) was signi?cantly longer than that of the decitabine group(18 months)(P = 0.043). The OS rates of 1, 2, and 3 years were signi?cantly higher in the QHP group(88.9%, 59.3%, 29.6%) than that in the decitabine group(70%, 25%, and 5%)(P = 0.01). There was no signi?cant difference of 5-year OS rate between the 2 groups(P = 0.133).The effects of prognostic factors on mOS were further analyzed, and it was found that there was no signi?cant difference of m OS rate between the QHP group(29 months) and the decitabine group(21 months) in the patients with age 65 years old(P = 0.673). The mOS rate was signi?cantly longer in QHP group(28.5 months) than that in decitabine group(18 months) in the patients with age of < 65 years old(P = 0.04). The proportions of bone marrow blast cells with 10% or < 10% had no signi?cant effects on the mOS rate of patients in the 2 groups(P = 0.429, P = 0.183). In patients with HGB 80 g/L, mOS rate was signi?cantly longer in the QHP group(57 months) than that in the decitabine group(21 months)(P = 0.047), while in patients with HGB < 80 g/L, there was no signi?cant difference of mOS rate between the 2 groups(P = 0.265). In the patients with PLT < 50×10~9/L, the mOS rate was signi?cantly longer in the QHP group(33 months) than that in the decitabine group(16 months)(P = 0.028). In the patients with PLT 50×10~9/L, there was no signi?cant difference of the mOS rate between the 2 groups(P = 0.338). In the patients with ANC < 0.8×10~9/L, the mOS rate was signi?cantly longer in the QHP group(20 months) than that in the decitabine group(7 months)(P = 0.014). In the patients with normal karyotype, the mOS was signi?cantly longer in the QHP group(32 months) than that in the decitabine group(15 months)(P = 0.009). In the patients with abnormal karyotypes, there was no significant difference of the mOS rate between the 2 groups(P = 0.882). In the patients with good karyotypes, the mOS rate was signi?cantly longer in the QHP group(37 months) than that in the decitabine group(20 months)(P = 0.019). In the patients with moderate/poor/very poor karyotype, there was no signi?cant difference of the mOS rate between the 2 groups(P = 0.685). In the patients with CCI 3, the mOS rate was signi?cantly longer in the QHP group(34 months) than that in the decitabine group(10.5 months)(P = 0.017). In patients with CCI < 3, there was no signi?cant difference of the mOS rate between the 2 groups(P = 0.581). The proportion of progression to AML in the QHP group(18.8%) was signi?cantly lower than that in the decitabine group(25%)(P = 0.03). CONCLUSION: Compared with decitabine, oral administration of arsenic-containing Qinghuang Powder could help patients to survive longer and decrease incidence of progression to acute myeloid leukemia in the treatment of patients with high/very high MDS.展开更多
Objective: To study the value of clonal analysis to the early diagnosis of myelodysplastic syndrome (MDS). Methods: Four types of clonal analyses were performed on the bone marrow samples from 50 patients suspected of...Objective: To study the value of clonal analysis to the early diagnosis of myelodysplastic syndrome (MDS). Methods: Four types of clonal analyses were performed on the bone marrow samples from 50 patients suspected of MDS: (1) Conventional Cytogenetics (CC) for clonal chromosomal abnormalities; (2) BrdU-Sister Chromatid Differentiation (BrdU-SCD) for cell cycle kinetics; (3) Fluorescence in Situ Hybridization (FISH) for trisomy 8; (4) Polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) for N-ras mutation. Results: The diagnosis of forty-three patients was compatible with the FAB criteria for MDS. The other seven cases didn’t meet the FAB criteria, with only one lineage of dyspoiesis or with no obvious dysplastic changes. Among these seven cases, two were morphologically diagnosed with suspicious refractory anemia, one with sideroblastic anemia, one with leukemoid reaction, one with hypercellular anemia and two with chronic aplastic anemia. Clonal analyses of the 7 patients showed that six cases had clonal karyotype abnormalities, four had prolonged cell cycle patterns, four had trisomy 8 of different proportions and one had mutation of the exon 1 of N-RAS. Thus, they were revaluated as MDS patients. Conclusion: The untypical MDS patients with one lineage dyspoiesis or without obvious dysplastic changes can be diagnosed early by combining multiple clonal analysis techniques such as CC, SCD, FISH and PCR-SSCR.展开更多
Myelodysplastic syndromes(MDS)are highly heterogeneous myeloid neoplasms,and a large number of patients are difficult to diagnose and classify by blood and bone marrow examination.As a surface marker of granulocyte,st...Myelodysplastic syndromes(MDS)are highly heterogeneous myeloid neoplasms,and a large number of patients are difficult to diagnose and classify by blood and bone marrow examination.As a surface marker of granulocyte,studies have shown CD10 can be used to define the degree of granulocyte maturation in MDS patients.However,whether it can be used for differential diagnosis of MDS and other hematological diseases remains inconclusive.To explore the value of CD10 for differential diagnosis of MDS,60 newly diagnosed MDS,20 aplastic anemia(AA)patients,and 35 iron-deficient anemia(IDA)patients were selected for this study.Bone marrow(BM)specimens were processed for surface marker analysis and labeled with pre-conjugated monoclonal antibodies.Stained cells were detected by flow cytometry.Our results indicated that CD10-positive granulocytes were significantly decreased in BM of MDS patients than AA and IDA patients,and the level of CD10-positive mature granulocytes was not associated with the clinical stages of malignancy.Receiver operating characteristic(ROC)areas under the curve(AUC)of CD10-positive granulocytes was 0.86 and 0.85,respectively,in MDS patients than the IDA group and AA group with good specificity and sensitivity.Further,CD10-positive granulocytes were increased after effective treatment.In conclusion,we found the decrease in CD10-positive granulocytes has a differential diagnostic value of MDS.展开更多
基金China Academy of Chinese Medical Sciences Innovation Fund:Precise Positioning Decision-making Platform for Clinical Trials of Traditional Chinese Medicine Based on Predicition Model(CI2021A04707)The Fundamental Research Funds for the Central Public Welfare Research Institutes:Research on Traditional Chinese Medicine Syndrome Differentiation-based a Bayesian Decision Model of Basket Trial(ZZ13-YQ-076)+1 种基金The Fifth Batch of National TCM Clinical Outstanding Talent Training ProgramThe Fund of National Natural Science Foundation of China(Youth Science):Effect of Compound Shenlu Granule on Apoptosis of CD34+Cells in Lower-risk Myelodysplastic Syndromes Bone Marrow based on p38 Mitogen-activated Protein Kinase Pathway(81403233)。
文摘OBJECTIVE:To illustrate the effect of add-on therapy of Traditional Chinese Medicine(TCM)on the long-term survival of anemic lower-risk myelodysplastic syndromes(LR-MDS)patients.METHODS:In this study,we conducted a retrospective analysis of the data of patients with LR-MDS who were identified from Shuguang Hospital between January 2006 and June 2020.The Kaplan-Meier method was used to calculate overall survival(OS),while the Cox model was employed to analyze prognostic factors of long-term survival.A total of 162 patients who met the inclusion criteria were divided into two groups:the TCM group(n=78)or the non-TCM group(n=84).RESULTS:There were no significant differences in baseline characteristics.The cumulative survival rate of the TCM group was significantly higher than that of the non-TCM group[log-rank P=0.029,hazard ratio(HR)=0.484,95%confidence interval(CI)(0.249,0.942),P<0.05].Patients with longer TCM treatment appeared to have better OS(≥12 months vs<12 months);[HR,0.16695%CI(0.055,0.508),P<0.001].According to the Cox model analysis,the combination of TCM and conventional Western Medicine may be a protective factor affecting the long-term survival of LR-MDS patients[HR=0.509,95%CI,(0.261,0.993),P=0.048].The hematologic improvement erythroid response(HI-E)rate of the TCM group was significantly higher than that of the non-TCM group(69.23%vs 52.38%;P=0.028).However,the duration of HI-E and cases of disease progression after HI-E did not significantly differ from the non-TCM group(P>0.05).CONCLUSIONS:The integration of TCM and Western Medicine has the potential to extend the OS of LR-MDS patients when compared to the use of Western Medicine alone.
基金partly supported by grants from the Beijing Municipal Science and Technology Commission(No.Z221100007422008)。
文摘Objective:Allogeneic hematopoietic stem cell transplantation(allo-HSCT)is the only potentially curative method for treating myelodysplastic syndrome(MDS).Post-HSCT measurable residual disease(post-HSCT MRD)is associated with inferior transplant outcomes.In this prospective study,we aimed to investigate the prognostic value of post-HSCT MRD in relapse prediction in MDS.Methods:A total of 166 patients diagnosed with MDS were prospectively enrolled in this study.The KaplanMeier method was used to calculate the survival probabilities.Potential risk factors for outcomes after transplantation were evaluated through univariate and multivariate Cox regression models.Results:For patients with negative and positive post-HSCT MRD,the cumulative incidence of relapse(CIR)and disease-free survival(DFS)at 3 years were 5.9%and 69.6%(P<0.001)and 82.7%and 26.1%(P<0.001),respectively.In the multivariate analysis,post-HSCT MRD(HR=22.801,P<0.001)and Revised International Prognostic Scoring System(IPSS-R)risk stratification(HR=4.346,P=0.003)were independently correlated with relapse.A scoring system for relapse prediction was built based on post-HSCT MRD and IPSS-R stratification.The cumulative incidence of relapse at 3 years was 1.1%,15.8%,and 91.7%for patients with scores of 0,1,and 2,respectively(P<0.001).Conclusions:Our results demonstrated both post-HSCT MRD and IPSS-R scores were independent prognostic factors for OS,DFS,and relapse for MDS patients after allo-HSCT.The risk score system could better predict transplant outcomes and refine the risk stratification than alone in patients with MDS.
文摘Objective:To explore the difference of lymphocyte subsets in peripheral blood(PB)between aplastic anemia(AA)and hypoplastic myelodysplastic syndrome(hypo-MDS)patients,meanwhile to compare the clinical parameters obtained from PB and bone marrow(BM).Methods:The lymphocyte subsets in hypo-MDS(n=25)and.AA(n=33)patients were investigated by flow cytometry.Meanwhile,the differences in PB cell counts,biochemical indicators,BM cell counts and abnormal chromosomes between the two groups were analyzed.Results:The percentage of CD8^(+)T cells in AA group was significantly higher than that in hypo-MDS group(P=0.001),while the percentage of CD4^(+)T cells and the CD4^(+)/CD8^(+)ratio in AA group were obviously lower than those in hypo-MDS group(P=0.015 and 0.001,respectively).Furthermore,the proportion of CD4^(+)and CD8^(+)activated T(TA)cells,and memory Tregs in AA group was distinctly lower than those in hypo-MDS group(P=0.043,0.015 and 0.024,respectively).Nevertheless,the percentage of CD8^(+)naive T(TN)cells in AA patients was remarkably higher(P=0.044).And hypo-MDS patients had declined lymphocyte counts(P=0.025),increased levels of total bilirubin(TBil),lactate dehydrogenase(LDH),vitamin B12 and proportion of BM blasts than AA patients(P=0.019,0.023,0.027 and.0.045,respectively).Conclusion:In this study it was confirmed that the percentages of CD4^(+)and CD8^(+)TA cells,memory Tregs and CD8^(+)TN cells were significantly different between AA and hypo-MDS patients,which provide an essential basis for the identification of these two diseases.
文摘The myelodysplastic/myeloproliferative neoplasms(MDS/MPNs) are a unique group of hematologic malignancies characterized by concomitant myelodysplastic and myeloproliferative features. According to the 2008 WHO classification, the category includes atypical chronic myeloid leukemia(a CML), chronic myelomonocytic leukemia(CMML), juvenile myelomonocytic leukemia(JMML), MDS/MPN-unclassifiable(MDS/MPN-U), and the provisional entity refractory anemia with ring sideroblasts and thrombocytosis(RARS-T). Although diagnosis currently remains based on clinicopathologic features, the incorporation of nextgeneration platforms has allowed for the recent molecular characterization of these diseases which has revealed unique and complex mutational profiles that support their distinct biology and is anticipated to soon play an integral role in diagnosis,prognostication, and treatment. Future goals of research should include the development of disease-modifying therapies, and further genetic understanding of the category will likely form the foundation of these efforts.
基金Supported by China Academy of Chinese Medicine Scientific Foundation(ZZ13-YQ-010)National Natural Science Foundation of China(No.81603490)State Administration of Traditional Chinese Medicine Foundation(No.JDZX-2015264)。
文摘OBJECTIVE:To explore the relationship between the efficacy of realgar for the treatment of myelodysplastic syndromes with multilineage dysplasia(MDS-MLD)and arsenic concentration in the peripheral blood of patients.METHODS:In this prospective study,a total of 50 MDS-MLD patients were treated with traditional Chinese drugs containing realgar for 3 months in Xiyuan Hospital from March 2018 to January 2019.Routine blood examination as well as liver and kidney function were monitored before and after treatment.The concentration of arsenic in the peripheral blood was measured using an atomic fluorescence spectrometer after treatment.The correlation between clinical effect and arsenic concentration was analyzed by Spearman’s method.RESULTS:The treatment response rate was 54%.Two patients(4%)achieved complete remission,50%(25 of 50)showed hematologic improvement,and 23 patients had stable disease(23%).No disease progression was observed.Arsenic concentration in the peripheral blood ranged from 14.60 to 85.96μg/L.Clinical efficacy was positively correlated with arsenic concentration(P<0.05).The incidence of mild adverse reactions was 16%.CONCLUSION:A relatively high concentration of arsenic in the peripheral blood may improve the clinical efficacy of realgar in MDS-MLD patients.
基金supported by grants from NIH(No.1R01LM010185,1U01CA166886,and 1U01HL111560)
文摘Myelodysplastic syndromes have increased in frequency and incidence in the American population, but patient prognosis has not significantly improved over the last decade. Such improvements could be realized if biomarkers for accurate diagnosis and prognostic stratification were successfully identified. In this study, we propose a method that associates two state-of-the-art array technologies-single nucleotide polymorphism (SNP) array and gene expression array-with gene motifs considered transcription factor -binding sites (TFBS). We are particularly interested in SNP-containing motifs introduced by genetic variation and mutation as TFBS. The potential regulation of SNP-containing motifs affects only when certain mutations occur. These motifs can be identified from a group of co-expressed genes with copy number variation. Then, we used a sliding window to identify motif candidates near SNPs on gene sequences. The candidates were filtered by coarse thresholding and fine statistical testing. Using the regression-based LARS-EN algorithm and a level-wise sequence combination procedure, we identified 28 SNP-containing motifs as candidate TFBS. We confirmed 21 of the 28 motifs with ChIP-chip fragments in the TRANSFAC database. Another six motifs were validated by TRANSFAC via searching binding fragments on coregulated genes. The identified motifs and their location genes can be considered potential biomarkers for myelodysplastic syndromes. Thus, our proposed method, a novel strategy for associating two data categories, is capable of integrating information from different sources to identify reliable candidate regulatory SNP-containing motifs introduced by genetic variation and mutation.
文摘AIM To evaluate factors associated with Clostridium difficile infection(CDI)and outcomes of CDI in the myelodysplastic syndrome(MDS)and acute myeloid leukemia(AML)population.METHODS After IRB approval,all MDS/AML patients hospitalized at the University of Maryland Greenebaum Comprehensive Cancer Center between August 2011 and December 2013 were identified.Medical charts were reviewed for demographics,clinical information,development of CDI,complications of CDI,and mortality.Patients with CDI,defined as having a positive stool PCR done for clinical suspicion of CDI,were compared to those without CDI in order to identify predictors of disease.A t-test was used for comparison of continuous variables and chisquare or Fisher's exact tests were used for categorical variables,as appropriate.RESULTS Two hundred and twenty-three patients(60.1%male,mean age 61.3 years,13%MDS,87%AML)had 594 unique hospitalizations during the study period.Thirtyfour patients(15.2%)were diagnosed with CDI.Factors significantly associated with CDI included lower albumin at time of hospitalization(P<0.0001),prior diagnosis of CDI(P<0.0001),receipt of cytarabine-based chemotherapy(P=0.015),total days of neutropenia(P=0.014),and total days of hospitalization(P=0.005).Gender(P=0.10),age(P=0.77),proton-pump inhibitor use(P=0.73),receipt of antibiotics(P=0.66),and receipt of DNA hypomethylating agent-based chemotherapy(P=0.92)were not significantly associated with CDI.CONCLUSION CDI is common in the MDS/AML population.Factors significantly associated with CDI in this population include low albumin,prior CDI,use of cytarabine-based chemotherapy,and prolonged neutropenia.In this study,we have identified a subset of patients in which prophylaxis studies could be targeted.
文摘Behet's disease is characterized by recurrent oral ulcers, genital ulcers, uveitis and skin lesions. Myelodysplastic syndrome (MDS) is characterized by problems due to ineffective hematopoiesis. Several studies have identified a relationship between MDS and Behet's disease, especially intestinal Behet's disease. Trisomy 8 seems to play an important role in these disorders as well. The present case was a 24-year-old woman who had a huge tonsil ulcer with initial symptoms of odynophagia and intermittent fever. We also noted folliculitis on her upper back. Five days later, she began to experience diarrhea and abdominal pain. Abdominal computed tomography and subsequent surgery revealed ileum perforation and enterocolitis with multiple ulcers. Later, she was admitted again for a vulvar suppurative ulcer and suspicious Bartholin's cyst infection. The patient's clinical presentations met the criteria for Behet's disease. Six months after the bowel perforation event, we noted the development of pancytopenia in a routine laboratory examination. All the examinations led to the diagnosis of MDS with trisomy 8. The most unusual finding was that multiple large vessel thrombi developed during follow-up. Previous studies have suggested that trisomy 8 in MDS leads to concurrent intestinal Behet's disease. Moreover, the inflammatory and immune genes related to thrombus formation are overexpressed in cases of MDS with trisomy 8. Trisomy 8 must play a role in thrombosis. Further studies are needed to help clarify the pathophysiology and pathogenesis of these disorders.
基金Supported by National Natural Science Foundation of China,No.81701600.
文摘BACKGROUND Ankylosing spondylitis(AS)is an autoimmune disease characterized by sacroiliitis and spondylitis,with a few hematological abnormalities.Myelodysplastic syndromes(MDS)are a heterogeneous group of hematopoietic stem cell disorders with frequent autoimmune phenomena.The relationship between AS and MDS remains unknown.CASE SUMMARY We describe a rare case of concurrent AS and MDS.An 18-year-old man with low back pain and anemia was diagnosed with AS;however,the cause of anemia could not be determined by the first bone marrow examination.He recovered from anemia and the symptoms of AS resolved after treatment with etanercept,glucocorticoid,and blood transfusion,but he developed pancytopenia with an increased myeloblast count(from 2.5%to 9%).Chromosome analysis revealed del(7q)and trisomy 8.Refractory anemia with excess of blasts-1(RAEB-1)/MDS was confirmed by repeating the bone marrow examination.He became blood transfusion-dependent and received decitabine-based chemotherapy but eventually died.CONCLUSION We suspect that AS may be an early autoimmune phenomenon related to MDS.However,a condition of coexistence cannot be excluded.
基金the National Natural Science Foundation of China(No.81470009).
文摘Distinguishing between aplastic anemia(AA)and hypoblastic myelodysplastic syndrome(hMDS)with a low percentage of bone marrow(BM)blasts(<5%)can be difficult due to the overlap in clonality and a spectrum of genetic alternations between the two subtypes of diseases.However,due to recent advances in DNA sequencing technology,both spectnim and frequency of mutations can be accurately determined and monitored by next-generation sequencing(NGS)at initial diagnosis and during immunosuppressive therapy(1ST)in patients with AA or hMDS.This improvement in acquiring a patient's genetic status and clonal evolution can provide more proper,precise,and on-time information to guide disease management,which is especially helpful in the absence of traditional morphologic/cytogenetic evidence.
基金supported by grants from the National Natural Science Foundation of China(No.30971286, 30971285,81170472)Chinese Medical Association of Molecular Biology Clinical Application Research Special Funds(No.CAMB042010)+1 种基金The"Eleventh Five-year Plan"National Science and Technology Support Plan(No. 2008BA161B00)Health Industry Research Special Project (No.201002024)
文摘Objective To investigate the expression of TET2 mRNA and protein in the bone marrow mononuclear cells （BMMNC） of patients with myelodysplastic syndrome （MDS） and its clinical significance. Methods The expression of TET2 mRNA and protein in bone marrow mononuclear cells （BMMNC） of 32 patients with MDS and 20 healthy donors was examined by qPCR and Western blot. Results The expression of TET2 mRNA in BMMNC was down-regulated in MDS patients compared with the donor group [（0.41±0.28）% vs. （1.07±0.56）%] （P〈0.001）. Compared with lower expression group （TET2〈0.4） [（6.53±6.17）%], patients with higher expression of TET2 ≥0.4） presented significantly lower proportion of bone marrow blasts [（1.21±1.56）%1 （P〈0.05）. The expression of TET2 mRNA in BMMNC of MDS patients was inversely correlated with malignant clone burden （t=--0.398, P〈0.05） and IPSS r=-0.412, P〈0.05）. The expression of TET2 protein was down-regulated in MDS patients compared with that in the donor group. Conclusions The mRNA and protein expression of TET2 in BMMNC of MDS patients is decreased, which might be useful as an important parameter for the evaluation of MDS clone burden.
基金Major Project of Jinhua Science and Technology Bureaun,No.2021-3-025。
文摘BACKGROUND Patients with trisomy 8 consistently present with myeloid neoplasms and/or auto-inflammatory syndrome.A possible link between myelodysplastic syndromes(MDS)with trisomy 8(+8-MDS)and inflammatory disorders is well recognized,several cases having been reported.However,inflammatory disorders in patients without MDS have been largely overlooked.Generally,Behçet's disease is the most common type in+8-MDS.However,inflammatory disorders with pulmonary involvement are less frequent,and no effective treatment has been established.CASE SUMMARY A 27-year-old man with recurrent fever,fatigue for>2 mo,and unconsciousness for 1 day was admitted to our emergency department with a provisional diagnosis of severe pneumonia.Vancomycin and imipenem were administered and sputum collected for metagenomic next-generation sequencing.Epstein–Barr virus and Mycobacterium kansasii were detected.Additionally,chromosomal analysis showed duplications on chromosome 8.Two days later,repeat metagenomic next-generation sequencing was performed with blood culture.Cordyceps portugal,M.kansasii,and Candida portugal were detected,and duplications on chromosome 8 confirmed.Suspecting hematological disease,we aspirated a bone marrow sample from the iliac spine,examination of which showed evidence of infection.We added fluconazole as further antibiotic therapy.Seven days later,the patient’s condition had not improved,prompting addition of methylprednisolone as an anti-inflammatory agent.Fortunately,this treatment was effective and the patient eventually recovered.CONCLUSION Severe inflammatory disorders with pulmonary involvement can occur in patients with trisomy 8.Methylprednisolone may be an effective treatment.
基金This work was supported by the National Natural Science Foundation of China(No.81770168 and No.81570110).
文摘Objective:Although the effect of decitabine on myelodysplastic syndrome(MDS)has been demonstrated,merely a proportion of patients respond to therapy,and no well-recognized predictors have been identified.This study was conducted to investigate the effectiveness of decitabine in real-world clinical practice,and determine the predictive factors of response and overall survival(OS)in MDS patients.
基金Supported by a grant from the Tianjin Natural Science Fund (013111111,023609311).
文摘Objective To investigate the role of the burden of abnormal hematopoietic clone in the development of myelodysplastic syndromes (MDS). Methods The ratio of the bone marrow cells with abnormal chromosomes to the total counted bone marrow cells was regarded as the index of MDS clone burden. The disease severity related parameters including white blood cell count, hemoglobin, platelet count, lactate dehydrogenase level, bone marrow blast, myeloid differentiation index, micromegakaryocyte, transfusion, interleukin-2, tumor necrosis factor (TNF), CD4^+ and CD8^+ T cells of MDS patients were assayed, and the correlations between those parameters and MDS clone burden were also analyzed. Results The clone burden of MDS patients was 67.4%±36.2%. MDS clone burden positively correlated with bone marrow blasts (r = 0.483, P<0.05), negatively with hemoglobin level (r=-0.445, P<0.05). The number of blasts, hemoglobin, and erythrocytes in high clone burden (>50%) and low clone burden (≤50%) groups were 7.78%±5.51% and 3.45%±3.34%, 56.06±14.28 g/L and 76.40±24.44 g/L, (1.82±0.48)×10~ 12 /L and (2.32±0.66)×10~ 12 /L, respectively (all P<0.05). CD4^+ T lymphocytes of MDS patients and normal controls were (0.274±0.719)×10~ 9 /L and (0.455±0.206)×10~ 9 /L, respectively (P<0.05). CD8^+ T lymphocytes of MDS patients and normal controls were (0.240±0.150)×10~ 9 /L and (0.305±0.145)×10~ 9 /L, respectively. The serum level of interleukin-2 of MDS patients (6.29±3.58 ng/mL) was significantly higher than normal control (3.11±1.40 ng/mL, P<0.05). The serum level of TNF of MDS patients and normal control group were 2.42±1.79 ng/mL and 1.68±0.69 ng/mL, respectively. The ratio of CD4 to CD8 was higher in high clone burden MDS patients (1.90±0.52) than that in low clone burden patients (0.97±0.44, P<0.05). Conclusion The quantitive clonal karyotype abnormalities and deficient T cell immunity are important parameters for evaluating MDS severity and predicting its progression.
基金National Science and Technology Major Project,Grant/Award Number:2017ZX10304402Peking Union Medical College,Grant/Award Number:3332020050。
文摘Background:Myelodysplastic syndrome(MDS)is a group of disorders involving he-mopoietic dysfunction leading to leukemia.Although recently progress has been made in identifying underlying genetic mutations,many questions still remain.Animal models of MDS have been produced by introduction of specific mutations.However,there is no spontaneous mouse model of MDS,and an animal model to simulate natu-ral MDS pathogenesis is urgently needed.Methods:In characterizing the genetically diverse mouse strains of the Collaborative Cross(CC)we observed that one,designated JUN,had abnormal hematological traits.This strain was thus further analyzed for phenotypic and pathological iden-tification,comparing the changes in each cell population in peripheral blood and in bone marrow.Results:In a specific-pathogen free environment,mice of the JUN strain are rela-tively thin,with healthy appearance.However,in a conventional environment,they become lethargic,develop wrinkled yellow hair,have loose and light stools,and are prone to infections.We found that the mice were cytopenic,which was due to abnor-mal differentiation of multipotent bone marrow progenitor cells.These are common characteristics of MDS.Conclusions:A mouse strain,JUN,was found displaying spontaneous myelodysplas-tic syndrome.This strain has the advantage over existing models in that it develops MDS spontaneously and is more similar to human MDS than genetically modified mouse models.JUN mice will be an important tool for pathogenesis research of MDS and for evaluation of new drugs and treatments.
基金supported by National Natural Science Foundation of China(No.81170472)Chinese Medical Association Molecular Biology Clinical Application Research Special Funds(No.CAMB042010)Tianjin Application Bases and Advanced Technology Research Program(No.09JCYBJC11200)
文摘Objective This study aims to investigate the expression of delta-like 1 （DLK1） gene in the bone marrow cells of patients with myelodysplastic syndromes （MDS） and to explore its molecular characteristics for the early diagnosis of MDS. Methods The expression of DLK1 mRNA in the bone marrow cells of cases with MDS, acute myeloid leukemia （AML）, and normal control groups were measured by real-time polymerase chain reaction and were analyzed for clinical significance. Results Significantly higher expression of DLK1 mRNA was observed in the bone marrow cells of MDS patients （0.7342±0.3652） compared with the normal control group （0.4801±0.1759） （P〈0.05）. The expression of DLK1 mRNA had a positive correlation with the proportion of bone marrow blasts （r=0.467, P〈0.05）. Moreover, DLK1 mRNA expression was significantly increased as MDS progressed （P〈0.05）. Patients with abnormal karyotypes exhibited significantly higher expression of DLK1 mRNA （0.9007±0.4334） than those with normal karyotypes （0.6411±0.2630） （P〈0.05）. Subsequently, patients with highly expressed DLK1 （≥0.8） presented significantly higher malignant clone burden （0.4134±0.3999） than those with lower DLK1 expression （〈0.8）,（0.1517±0.3109）, （P〈0.05）. Conclusions The DLK1 gene was highly expressed in MDS patients, and was increased as MDS progressed. The expression of DLK1 mRNA was positively correlated with the proportion of the bone marrow blasts. A high expression of DLK1 gene suggested a higher malignant clone burden of MDS.
基金Supported by The Specialized Scientific Research Fund Projects of The Medical Group of Qingdao University,No.YLJT20201002.
文摘BACKGROUND Myelodysplastic syndrome(MDS)is a hematological neoplasm,and an increase in myeloblasts is representative of leukemic hematopoiesis in advanced MDS.Lowrisk MDS usually exhibits deranged autoimmunity resembling that of aplastic anemia(AA),whereas advanced MDS is characterized by a phenotype of immune exhaustion.MDS can be normo/hyperplastic or hypoplastic.Generally,bone marrow cellularity and myeloblasts increase with disease progression.Transformation from advanced MDS to AA-like syndrome with leukemic cell regression has not previously been reported.CASE SUMMARY A middle-aged Chinese woman had a 4-year history of leukocytopenia.Six months prior to admission,the patient developed gradually worsening fatigue and performance status.The leukocytopenia further progressed.She was diagnosed with MDS with excess blasts-2 based on increased bone marrow cellularity and an increased percentage of myeloblasts on marrow and blood smears,an increased percentage of cluster of differentiation(CD)34+CD33+progenitors in immunotyping analysis,a normal karyotype in cytogenetic analysis,and the identification of somatic mutations in CBL,KMT2D and NF1 in molecular analysis.Initially,neutropenia was the predominant hematological abnormality,with mild anemia and thrombocytosis,and the degree of fatigue was far more severe than the degree of anemia.In the following months,the patient experienced several febrile episodes.Intravenous antibiotic treatments were able to control the febrile episodes,but the elevated inflammatory indices persisted.The hematological parameters dramatically fluctuated with the waxing and waning of the inflammatory episodes.With recurrent flares of the inflammatory condition,agranulocytosis and severe anemia developed,with mild thrombocytopenia.During the patient’s hospitalization,computed tomography(CT)scans revealed the presence of extensive inflammatory lesions involving the lungs,mediastinum,pleura,gastrointestinal tract,peritoneum and urinary tract,with imaging features suggestive of the reactivation of disseminated tuberculosis.Reevaluation of the bone marrow smears revealed that the cellularity became hypoplastic,and the leukemic cells regressed,suggesting that both normal and leukemic hematopoiesis had been heavily suppressed.Immunological analysis of the bone marrow samples revealed a decreased percentage of CD34+cells and an immunological signature resembling that of severe AA(SAA),confirming the regression of the leukemic cells by autoimmune-mediated attacks.The patient demonstrated resistance to multiple drugs,including antituberculotics,recombinant human granulocyte colony-stimulating factor,broad-spectrum antibiotics,voriconazole,ganciclovir,immune suppressants,eltrombopag and intravenous immunoglobulin,which further worsened the hematological injury and patient’s performance status.The patient eventually died of overwhelming infection and multidrug resistance.CONCLUSION Advanced MDS can transform to aplastic cytopenia with leukemic cell regression and an immunological signature of SAA during inflammatory flare-ups.
基金supported by National Natural Science Foundation of China(81673821)National Natural Science Foundation of China(81774142)+1 种基金Central Level Research Institute of Public Welfare Research Funds(ZZ10-016)National TCM Clinical Research Base Business Construction Second Batch of Scientific Research Projects(JDZX2015264)
文摘OBJECTIVE: To evaluated the benefits of oral administration of arsenic-containing Qinghuang Powder(QHP)compared with decitabine for patients with high/very-high(H/VH) risk myelodysplastic syndrome(MDS) according to the Revised International Prognostic Score System. METHODS: The OS(mOS) rate, annual OS rate and progression to acute myeloid leukemia(AML) in patients with H/VH MDS treated with QHP(QHP group, n = 27) and decitabine(decitabine group, n = 20) were retrospectively analyzed. The effects of prognostic factors of age, proportion of bone marrow blast,peripheral blood cell count, karyotype and Charlson Comorbidity Index(CCI) on OS were further analyzed. RESULTS: The m OS rate of QHP group(29 months) was signi?cantly longer than that of the decitabine group(18 months)(P = 0.043). The OS rates of 1, 2, and 3 years were signi?cantly higher in the QHP group(88.9%, 59.3%, 29.6%) than that in the decitabine group(70%, 25%, and 5%)(P = 0.01). There was no signi?cant difference of 5-year OS rate between the 2 groups(P = 0.133).The effects of prognostic factors on mOS were further analyzed, and it was found that there was no signi?cant difference of m OS rate between the QHP group(29 months) and the decitabine group(21 months) in the patients with age 65 years old(P = 0.673). The mOS rate was signi?cantly longer in QHP group(28.5 months) than that in decitabine group(18 months) in the patients with age of < 65 years old(P = 0.04). The proportions of bone marrow blast cells with 10% or < 10% had no signi?cant effects on the mOS rate of patients in the 2 groups(P = 0.429, P = 0.183). In patients with HGB 80 g/L, mOS rate was signi?cantly longer in the QHP group(57 months) than that in the decitabine group(21 months)(P = 0.047), while in patients with HGB < 80 g/L, there was no signi?cant difference of mOS rate between the 2 groups(P = 0.265). In the patients with PLT < 50×10~9/L, the mOS rate was signi?cantly longer in the QHP group(33 months) than that in the decitabine group(16 months)(P = 0.028). In the patients with PLT 50×10~9/L, there was no signi?cant difference of the mOS rate between the 2 groups(P = 0.338). In the patients with ANC < 0.8×10~9/L, the mOS rate was signi?cantly longer in the QHP group(20 months) than that in the decitabine group(7 months)(P = 0.014). In the patients with normal karyotype, the mOS was signi?cantly longer in the QHP group(32 months) than that in the decitabine group(15 months)(P = 0.009). In the patients with abnormal karyotypes, there was no significant difference of the mOS rate between the 2 groups(P = 0.882). In the patients with good karyotypes, the mOS rate was signi?cantly longer in the QHP group(37 months) than that in the decitabine group(20 months)(P = 0.019). In the patients with moderate/poor/very poor karyotype, there was no signi?cant difference of the mOS rate between the 2 groups(P = 0.685). In the patients with CCI 3, the mOS rate was signi?cantly longer in the QHP group(34 months) than that in the decitabine group(10.5 months)(P = 0.017). In patients with CCI < 3, there was no signi?cant difference of the mOS rate between the 2 groups(P = 0.581). The proportion of progression to AML in the QHP group(18.8%) was signi?cantly lower than that in the decitabine group(25%)(P = 0.03). CONCLUSION: Compared with decitabine, oral administration of arsenic-containing Qinghuang Powder could help patients to survive longer and decrease incidence of progression to acute myeloid leukemia in the treatment of patients with high/very high MDS.
文摘Objective: To study the value of clonal analysis to the early diagnosis of myelodysplastic syndrome (MDS). Methods: Four types of clonal analyses were performed on the bone marrow samples from 50 patients suspected of MDS: (1) Conventional Cytogenetics (CC) for clonal chromosomal abnormalities; (2) BrdU-Sister Chromatid Differentiation (BrdU-SCD) for cell cycle kinetics; (3) Fluorescence in Situ Hybridization (FISH) for trisomy 8; (4) Polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) for N-ras mutation. Results: The diagnosis of forty-three patients was compatible with the FAB criteria for MDS. The other seven cases didn’t meet the FAB criteria, with only one lineage of dyspoiesis or with no obvious dysplastic changes. Among these seven cases, two were morphologically diagnosed with suspicious refractory anemia, one with sideroblastic anemia, one with leukemoid reaction, one with hypercellular anemia and two with chronic aplastic anemia. Clonal analyses of the 7 patients showed that six cases had clonal karyotype abnormalities, four had prolonged cell cycle patterns, four had trisomy 8 of different proportions and one had mutation of the exon 1 of N-RAS. Thus, they were revaluated as MDS patients. Conclusion: The untypical MDS patients with one lineage dyspoiesis or without obvious dysplastic changes can be diagnosed early by combining multiple clonal analysis techniques such as CC, SCD, FISH and PCR-SSCR.
基金the National Natural Science Foundation of China(81670179)Research Fund Project of Anhui Medical University(No.2018xkj026)National Natural Science Foundation Incubation Project of the Second Hospital of Anhui Medical University(Grant No.2019GQFY11).
文摘Myelodysplastic syndromes(MDS)are highly heterogeneous myeloid neoplasms,and a large number of patients are difficult to diagnose and classify by blood and bone marrow examination.As a surface marker of granulocyte,studies have shown CD10 can be used to define the degree of granulocyte maturation in MDS patients.However,whether it can be used for differential diagnosis of MDS and other hematological diseases remains inconclusive.To explore the value of CD10 for differential diagnosis of MDS,60 newly diagnosed MDS,20 aplastic anemia(AA)patients,and 35 iron-deficient anemia(IDA)patients were selected for this study.Bone marrow(BM)specimens were processed for surface marker analysis and labeled with pre-conjugated monoclonal antibodies.Stained cells were detected by flow cytometry.Our results indicated that CD10-positive granulocytes were significantly decreased in BM of MDS patients than AA and IDA patients,and the level of CD10-positive mature granulocytes was not associated with the clinical stages of malignancy.Receiver operating characteristic(ROC)areas under the curve(AUC)of CD10-positive granulocytes was 0.86 and 0.85,respectively,in MDS patients than the IDA group and AA group with good specificity and sensitivity.Further,CD10-positive granulocytes were increased after effective treatment.In conclusion,we found the decrease in CD10-positive granulocytes has a differential diagnostic value of MDS.
