BACKGROUND Patients with severe aplastic anemia(SAA)frequently present with inflammatory episodes,and during flared inflammatory episodes,hematopoietic function is further exacerbated.The gastrointestinal tract is the...BACKGROUND Patients with severe aplastic anemia(SAA)frequently present with inflammatory episodes,and during flared inflammatory episodes,hematopoietic function is further exacerbated.The gastrointestinal tract is the most common site for infectious and inflammatory diseases,and its structural and functional features confer on it the most potent capacity to affect hematopoietic and immune functions.Computed tomography(CT)is a readily accessible approach to provide highly useful information in detecting morphological changes and guiding further work-ups.AIM To explore CT imaging presentations of gut inflammatory damage in adult SAA patients during inflammatory episodes.METHODS We retrospectively evaluated the abdominal CT imaging presentations of 17hospitalized adult patients with SAA in search of the inflammatory niche when they presented with systemic inflammatory stress and exacerbated hematopoietic function.In this descriptive manuscript,the characteristic images that suggested the presence of gastrointestinal inflammatory damage and related imaging presentations of individual patients were enumerated,analyzed and described.RESULTS All eligible patients with SAA had CT imaging abnormalities that suggested the presence of an impaired intestinal barrier and increased epithelial permeability.The inflammatory damages were concurrently present in the small intestine,the ileocecal region and the large intestines.Some readily identified imaging signs,such as bowel wall thickening with mural stratification(“water holo sign”,“fat holo sign”,intramural gas and subserosal pneumatosis)and mesenteric fat proliferation(fat stranding and“creeping fat sign”),fibrotic bowel wall thickening,“balloon sign”,rugged colonic configuration,heterogeneity in the bowel wall texture,and adhered and clustered small bowel loop(including various patterns of“abdominal cocoon”),occurred at a high incidence,which suggested that the damaged gastrointestinal tract is a common inflammatory niche responsible for the systemic inflammatory stresses and the exacerbated hematopoietic failure in patients with SAA.Particularly,the“fat holo sign”was present in 7 patients,a rugged colonic configuration was present in 10 patients,the adhesive bowel loop was present in 15 patients,and extraintestinal manifestations suggestive of tuberculosis infections were present in 5 patients.According to the imaging features,a suggestive diagnosis of Crohn’s disease was made in 5patients,ulcerative colitis in 1 patient,chronic periappendiceal abscess in 1 patient,and tuberculosis infection in 5 patients.Other patients were diagnosed with chronic enteroclolitis with acutely aggravated inflammatory damage.CONCLUSION Patients with SAA had CT imaging patterns that suggested the presence of active chronic inflammatory conditions and aggravated inflammatory damage during flared inflammatory episodes.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
BACKGROUND Accumulating evidence demonstrates that autoimmune hematopoietic failure and myeloid neoplasms have an intrinsic relationship with regard to clonal hematopoiesis and disease evolution.In approximately 10%-1...BACKGROUND Accumulating evidence demonstrates that autoimmune hematopoietic failure and myeloid neoplasms have an intrinsic relationship with regard to clonal hematopoiesis and disease evolution.In approximately 10%-15%of patients with severe aplastic anemia(SAA),the disease phenotype is transformed into myeloid neoplasms following antithymocyte globulin plus cyclosporine-based immunosuppressive therapy.In some of these patients,myeloid neoplasms appear during or shortly after immunosuppressive therapy.Leukemic transformation in SAA patients during anti-tuberculosis treatment has not been reported.CASE SUMMARY A middle-aged Chinese female had a 6-year history of non-SAA and a 2-year history of paroxysmal nocturnal hemoglobinuria(PNH).With aggravation of systemic inflammatory symptoms,severe pancytopenia developed,and her hemoglobinuria disappeared.Laboratory findings in cytological,immunological and cytogenetic analyses of bone marrow samples met the diagnostic criteria for“SAA.”Definitive diagnosis of disseminated tuberculosis was made in the search for infectious niches.Remarkable improvement in hematological parameters was achieved within 1 mo of anti-tuberculosis treatment,and complete hematological remission was achieved within 4 mo of treatment.Frustratingly,the hematological response lasted for only 3 mo,and pancytopenia reemerged.At this time,cytological findings(increased bone marrow cellularity and an increased percentage of myeloblasts that accounted for 16.0%of all nucleated hematopoietic cells),immunological findings(increased percentage of cluster of differentiation 34+cells that accounted for 12.28%of all nucleated hematopoietic cells)and molecular biological findings(identification of somatic mutations in nucleophosmin-1 and casitas B-lineage lymphoma genes)revealed that“SAA”had transformed into acute myeloid leukemia with mutated nucleophosmin-1.The transformation process suggested that the leukemic clones were preexistent but were suppressed in the PNH and SAA stages,as development of symptomatic myeloid neoplasm through acquisition and accumulation of novel oncogenic mutations is unlikely in an interval of only 7 mo.Aggravation of inflammatory stressors due to disseminated tuberculosis likely contributed to the repression of normal and leukemic hematopoiesis,and the relief of inflammatory stressors due to anti-tuberculosis treatment contributed to penetration of neoplastic hematopoiesis.The concealed leukemic clones in the SAA and PNH stages raise the possibility of an inflammatory stress-fueled antileukemic mechanism.CONCLUSION Aggravated inflammatory stressors can repress normal and leukemic hematopoiesis,and relieved inflammatory stressors can facilitate penetration of neoplastic hematopoiesis.展开更多
BACKGROUND Immunosuppressive therapy and matched sibling donor hematopoietic stem cell transplantation(MSD-HSCT)are the preferred treatments for aplastic anemia(AA).CASE SUMMARY In this report,we describe a 43-year-ol...BACKGROUND Immunosuppressive therapy and matched sibling donor hematopoietic stem cell transplantation(MSD-HSCT)are the preferred treatments for aplastic anemia(AA).CASE SUMMARY In this report,we describe a 43-year-old male patient with severe AA who carried BRIP1(also known as FANCJ),TINF2,and TCIRG1 mutations.Screening of the family pedigree revealed the same TINF2 mutation in his mother and older brother,with his older brother also carrying the BRIP1 variant and demonstrating normal telomere length and hematopoietic function.The patient was successfully treated with oral cyclosporine A,eltrombopag,and acetylcysteine,achieving remission 4 years after receiving MSD-HSCT from his older brother.CONCLUSION This case provides a valuable clinical reference for individuals with suspected pathogenic gene mutations,normal telomere length,and hematopoietic function,highlighting them as potential donors for patients with AA.展开更多
BACKGROUND Myelodysplastic syndrome(MDS)is caused by malignant proliferation and ineffective hematopoiesis.Oncogenic somatic mutations and increased apoptosis,necroptosis and pyroptosis lead to the accumulation of ear...BACKGROUND Myelodysplastic syndrome(MDS)is caused by malignant proliferation and ineffective hematopoiesis.Oncogenic somatic mutations and increased apoptosis,necroptosis and pyroptosis lead to the accumulation of earlier hematopoietic progenitors and impaired productivity of mature blood cells.An increased percentage of myeloblasts and the presence of unfavorable somatic mutations are signs of leukemic hematopoiesis and indicators of entrance into an advanced stage.Bone marrow cellularity and myeloblasts usually increase with disease progression.However,aplastic crisis occasionally occurs in advanced MDS.CASE SUMMARY A 72-year-old male patient was definitively diagnosed with MDS with excess blasts-1(MDS-EB-1)based on an increase in the percentages of myeloblasts and cluster of differentiation(CD)34+hematopoietic progenitors and the identification of myeloid neoplasm-associated somatic mutations in bone marrow samples.The patient was treated with hypomethylation therapy and was able to maintain a steady disease state for 2 years.In the treatment process,the advanced MDS patient experienced an episode of progressive pancytopenia and bone marrow aplasia.During the aplastic crisis,the bone marrow was infiltrated with sparsely distributed atypical lymphocytes.Surprisingly,the leukemic cells disappeared.Immunological analysis revealed that the atypical lymphocytes expressed a high frequency of CD3,CD5,CD8,CD16,CD56 and CD57,suggesting the activation of autoimmune cytotoxic T-lymphocytes and natural killer(NK)/NKT cells that suppressed both normal and leukemic hematopoiesis.Elevated serum levels of inflammatory cytokines,including interleukin(IL)-6,interferon-gamma(IFN-γ)and tumor necrosis factor-alpha(TNF-α),confirmed the deranged type I immune responses.This morphological and immunological signature led to the diagnosis of severe aplastic anemia secondary to large granule lymphocyte leukemia.Disseminated tuberculosis was suspected upon radiological examinations in the search for an inflammatory niche.Antituberculosis treatment led to reversion of the aplastic crisis,disappearance of the atypical lymphocytes,increased marrow cellularity and 2 mo of hematological remission,providing strong evidence that disseminated tuberculosis was responsible for the development of the aplastic crisis,the regression of leukemic cells and the activation of CD56+atypical lymphocytes.Reinstitution of hypomethylation therapy in the following 19 mo allowed the patient to maintain a steady disease state.However,the patient transformed the disease phenotype into acute myeloid leukemia and eventually died of disease progression and an overwhelming infectious episode.CONCLUSION Disseminated tuberculosis can induce CD56+lymphocyte infiltration in the bone marrow and in turn suppress both normal and leukemic hematopoiesis,resulting in the development of aplastic crisis and leukemic cell regression.展开更多
Background:To develop a protein-protein interaction network of Paroxysmal nocturnal hemoglobinuria(PNH)and Aplastic anemia(AA)based on genetic genes and to predict pathways underlying the molecular complexes in the ne...Background:To develop a protein-protein interaction network of Paroxysmal nocturnal hemoglobinuria(PNH)and Aplastic anemia(AA)based on genetic genes and to predict pathways underlying the molecular complexes in the network.Methods:In this research,the PNH and AA-related genes were screened through Online Mendelian Inheritance in Man(OMIM).The plugins and Cytoscape were used to search literature and build a protein-protein interaction network.Results:The protein-protein interaction network contains two molecular complexes that are five higher than the correlation integral values.The target genes of this study were obtained:CD59,STAT3,TERC,TNF,AKT1,C5AR1,EPO,IL6,IL10 and so on.We also found that many factors regulate biological behaviors:neutrophils,macrophages,vascular endothelial growth factor,immunoglobulin,interleukin,cytokine receptor,interleukin-6 receptor,tumor necrosis factor,and so on.This research provides a bioinformatics foundation for further explaining the mechanism of common development of both.Conclusion:This indicates that the PNH and AA is a complex process regulated by many cellular pathways and multiple genes.展开更多
Telaprevir and Boceprevir are the first direct acting antivirals approved for chronic hepatitis C in combination with peg-interferon alfa and ribavirin.Pancytopenia due to myelotoxicity caused by these drugs may occur...Telaprevir and Boceprevir are the first direct acting antivirals approved for chronic hepatitis C in combination with peg-interferon alfa and ribavirin.Pancytopenia due to myelotoxicity caused by these drugs may occur,but severe hematological abnormalities or aplastic anemia(AA) have not been described.We collected all cases of severe pancytopenia observed during triple therapy with telaprevir in four Spanish centers since approval of the drug in 2011.Among 142 cirrhotic patients receiving treatment,7 cases of severe pancytopenia(5%) were identified and three were consistent with the diagnosis of AA.Mean age was 59 years,five patients had compensated cirrhosis and two patients had severe hepatitis C recurrence after liver transplantation.Severe pancytopenia was diagnosed a median of 10 wk after the initiation of therapy.Three patients had pre-treatment hematological abnormalities related to splenomegaly.In six patients,antiviral treatment was interrupted at the onset of hematological abnormalities.Two patients died due to septic complications and one patient due to acute alveolar hemorrhage.The remaining patients recovered.Severe pancytopenia and especially AA,are not rare during triple therapy with telaprevir in patients with advanced liver disease.Close monitoring is imperative in this setting to promptly detect serious hematological disorders and to prevent further complications.展开更多
Recent studies indicate that immune-associated aplastic anemia(AA)resembles such autoimmune diseases as insulin-dependent diabetes and chronic autoimmune thyroiditis that belong to organ-specific autoimmune diseases.M...Recent studies indicate that immune-associated aplastic anemia(AA)resembles such autoimmune diseases as insulin-dependent diabetes and chronic autoimmune thyroiditis that belong to organ-specific autoimmune diseases.Many independent investigation groups have successfully isolated the pathopoiesis-associated T cell clone causing hematopoiesis failure with a CD4 phenotype from peripheral blood and bone marrow(BM)in AA patients.In the current study,BM CD4+ T cells were isolated from AA patients and healthy controls with immunomagnetic beads sorting,and proliferation capability,apoptosis features and the impacts of their secreted cytokines on hematopoiesis stem/progenitor cells were compared between them.By 3H-TdR method,CD4+ T cells in AA group presented more enhanced proliferative activity.The stimulation index in control group and AA group was 1.47±0.24,and 2.51±0.34 respectively(P<0.01).After BM CD4+ T cells were induced by high concentration of CD3 monoclonal antibody for 18 h,evident apoptosis cells could be seen under the electron microscope in both control group and AA group.Flow cytometry revealed that apoptosis rates in the early and late stages of AA group were significantly higher than in control group(P<0.01).Early-stage apoptosis rate in control and AA groups was(6.85±1.48)% and(16.98±4.40)%,and late-stage apoptosis rate in control group and AA group was(2.65±1.57)% and(7.74±0.83)%,respectively(P<0.01).The CFU-GM count in AA group and control group was(74.50±9.50)/104 cells and(124.25±19.80)/104 cells respectively under an inverted microscope(P<0.01),and the expression levels of CyclinD3 mRNA and protein in cord blood CD34+ cells were both down-regulated induced by BM CD4+ T cell culture supernatant in AA patients.These results indicate that BM CD4+ T cells of AA patients are likely in an abnormally proliferative,and activated state which can correlate intimately with AA hematopoiesis damage.BM CD4+ T cells in AA patients can secret some soluble cytokines that can inhibit proliferation of hematopoietic stem cells by suppressing the expression of Cyclin D3,resulting in hematopoiesis failure.展开更多
Acquired aplastic anemia(AA) is a bone marrow failure syndrome characterized by peripheral cytopenias and bone marrow hypoplasia. It is ultimately fatal without treatment, most commonly from infection or hemorrhage. C...Acquired aplastic anemia(AA) is a bone marrow failure syndrome characterized by peripheral cytopenias and bone marrow hypoplasia. It is ultimately fatal without treatment, most commonly from infection or hemorrhage. Current treatments focus on suppressing immune-mediated destruction of bone marrow stem cells or replacing hematopoietic stem cells(HSCs) by transplantation. Our incomplete understanding of the pathogenesis of AA has limited development of targeted treatment options. Mesenchymal stem cells(MSCs) play a vital role in HSC proliferation; they also modulate immune responses and maintain an environment supportive of hematopoiesis. Some of the observed clinical manifestations of AA can be explained by mesenchymal dysfunction. MSC infusions have been shown to be safe and may offer new approaches for the treatment of this disorder. Indeed, infusions of MSCs may help suppress auto-reactive, T-cell mediated HSC destruction and help restore an environment that supports hematopoiesis. Small pilot studies using MSCs as monotherapy or as adjuncts to HSC transplantation have been attempted as treatments for AA. Here we review the current understanding of the pathogenesis of AA and the function of MSCs, and suggest that MSCs should be a target for further research and clinical trials in this disorder.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
The content of 12 trace elements in the hair of 20 aplastic anemia patients was determined and compared with that of normal subjects as control. The results showed that patients with deficiency of yin had a significan...The content of 12 trace elements in the hair of 20 aplastic anemia patients was determined and compared with that of normal subjects as control. The results showed that patients with deficiency of yin had a significant decrease in lithium, calcium, strontium, and chromium, those with deficiency of yang had a distinct decrease in zinc magnesium barium, strontium, calcium, and lithium, and those with deficiency of both yin and yang had a general decrease in all the 12 trace elements. Changes in trace element content in hair may serve as a guide to opening up new vistas in the treatment of aplastic anemia on the basis of an overall analysis of symptoms and signs.展开更多
BACKGROUND Cumulative evidence suggests that the aberrant immune responses in acquired aplastic anemia(AA) are sustained by active chronic infections in genetically susceptible individuals. Recently, the constant sour...BACKGROUND Cumulative evidence suggests that the aberrant immune responses in acquired aplastic anemia(AA) are sustained by active chronic infections in genetically susceptible individuals. Recently, the constant source to trigger and sustain the pathophysiology has been proposed to come from the altered gut microbiota and chronic intestinal inflammation. In this case, our serendipitous finding provides convincing evidence that the persistently dysregulated autoimmunity may be generated, at least in a significant proposition of AA patients, by the altered gut microbiota and compromised intestinal epithelium.CASE SUMMARY A 30-year-old Chinese male patient with refractory severe AA experienced a 3-month-long febrile episode, and his fever was refractory to many kinds of injected broad-spectrum antibiotics. When presenting with abdominal cramps, he was prescribed oral mannitol and gentamycin to get rid of the gut infection. This treatment resulted in a quick resolution of the fever. Unanticipatedly, it also produced an excellent hematological response. He had undergone three episodes of recurrence within the one-year treatment, with each recurrence occurring 7-8 wk from the gastrointestinal inflammation eliminating preparations. However,subsequent treatments were able to produce subsequent remissions and consecutive treatments were successful in achieving durative hematological improvements, strongly indicating an etiological association between chronic gut inflammation and the development of AA. Interestingly, comorbid diseases superimposed on this patient(namely, psychiatric disorders, hypertension,insulin resistance, and renal dysfunction) were ameliorated together with the hematological improvements.CONCLUSION Chronic gut inflammation may be responsible for AA pathogenesis. The comorbidities and AA may share a common etiological association.展开更多
Rationale:Trichosporon,an anamorphic fungus,proliferates under high humidity,causing serious opportunistic infections collectively called trichosporonosis.Among the Trichosporon species causing trichosporonosis are Tr...Rationale:Trichosporon,an anamorphic fungus,proliferates under high humidity,causing serious opportunistic infections collectively called trichosporonosis.Among the Trichosporon species causing trichosporonosis are Trichosporon(T.)asahii,T.asteroides,T.cutaneum etc.Patient concerns:A 38-year-old Chinese male with severe aplastic anemia was admitted due to multiple joints pain,poor appetite,and right ankle swelling.One year earlier he had undergone allogeneic hematopoietic stem cell transplantation.Diagnosis:T.asahii infection and severe aplastic anemia.Interventions:Combined treatment of amphotericin B liposomes(55 mg/24 h)and voriconazole(200 mg/12 h)for 8 days.Outcomes:The symptoms of the patient’s ankle were relieved and effusion cultures showed no T.asahii.Lessons:To the best of our knowledge,T.asahii ankle cavity effusion infections are rare.Trichosporon infections may be attributed to risk factors such as improper long-term use of antimicrobials for an underlying disease(e.g.,anemia,hypoalbuminemia).Attention should be paid to prevent and control Trichosporon infections in order to avoid comorbidities.展开更多
A transjugular intrahepatic portal-systemic shunt (TIPS) is a standard way to decompress the portal system in cirrhotic patients as a bridge to orthotopic liver transplantation (OLT). Traditionally, TIPS has been indi...A transjugular intrahepatic portal-systemic shunt (TIPS) is a standard way to decompress the portal system in cirrhotic patients as a bridge to orthotopic liver transplantation (OLT). Traditionally, TIPS has been indicated for certain portal hypertensive sequelae such as refractory ascites, varices treatment and even hepato-hydrothorax. Herein is a case report on the efficacy of TIPS in an OLT ineligible patient with primary biliary cirrhosis and aplastic anemia who had developed refractive ascites requiring serial paracentesis and esophageal varices. He survived 2.5 years post-TIPS placement and died from complications related to severe leucopenia and the development of sepsis.展开更多
Chimeric antigen receptor(CAR)T-cell therapy is an effective new treatment strategy for hematologic malignancies.The success of CAR T-cell therapy in treating leukemia and lymphoma has promoted its development for mul...Chimeric antigen receptor(CAR)T-cell therapy is an effective new treatment strategy for hematologic malignancies.The success of CAR T-cell therapy in treating leukemia and lymphoma has promoted its development for multiple myeloma(MM),and the initial results of CAR T cell therapy have been encouraging.CAR T-cell therapy target antigens that have been clinically evaluated in MM;these antigens include CD19,B cell maturation antigen(BCMA),CD38,and CD138.A barrier to the widespread use of CAR T-cell therapy is its toxicity,primarily cytokine release syndrome(CRS),and neurologic toxicity.This study reports a patient with refractory MM who also developed megakaryocyte aplastic thrombocytopenia after receiving CAR T-cell therapy;such a case or the unusual side effects involving medications are yet unreported.There are risks in using cyclosporine and other immunosuppressants that may lead to MM recurrence as the use of such substances is contradictory to previous treatments;therefore,we temporarily administered platelet infusion as supportive care.Thus far,the condition of the patient has been steady and the patient regularly takes blood test in the hospital.展开更多
Objective:To reduce the potential risk in aplastic anemia patients complicated with Gilbert syndrome,and find an effective treatment for the unconjugated hyperbilirubinemia.Material and Methods:The mutation of UGT1A1 ...Objective:To reduce the potential risk in aplastic anemia patients complicated with Gilbert syndrome,and find an effective treatment for the unconjugated hyperbilirubinemia.Material and Methods:The mutation of UGT1A1 gene was identified first via sequencing in patients with Gilbert syndrome complicated by aplastic anemia.Before the treatment for aplastic anemia,bilirubin and phenobarbitone tests were conducted.Patients were then treated for their primary disease and given ursodeoxycholic acid(UDCA)either with or without phenobarbitone.Results:The clinical practice of UDCA,which can alleviate increased bilirubin levels,did not affect the key treatments for aplastic anemia.Conclusions:These results indicate that Gilbert syndrome should be addressed when treating aplastic anemia.Furthermore,abnormal bilirubin levels can be controlled effectively by the UDCA treatment.展开更多
IL-2 production and IL-2 receptor (Tac antigen) of the peripheral blood mononuclear cells in 30 patients with aplastic anemic (AA) were studied. We found that mononuclear cells from patients produce spontaneously IL-2...IL-2 production and IL-2 receptor (Tac antigen) of the peripheral blood mononuclear cells in 30 patients with aplastic anemic (AA) were studied. We found that mononuclear cells from patients produce spontaneously IL-2 in the absence of exogenous lee-tin stimulation, the proportion of Tac+ cells in mononuclear cells increased. The release of IL-2 and or Tac antigen expression were elevated in almost every patient with AA. The plasma from patients stimulate mitogen-induced blastogenesis and Tac antigen expression of normal human lymphocytes. Immunological 1 abnormalities of patients with AA possibly might represents secondary response to bone marrow depression.展开更多
Accelerating cell growth is one of the functions of thyroid hormone. In the absence or lack of this hormone, hematopoietic disorder may occur. Dynamic observation of thyroid function in aplastic anemia (AA) state has ...Accelerating cell growth is one of the functions of thyroid hormone. In the absence or lack of this hormone, hematopoietic disorder may occur. Dynamic observation of thyroid function in aplastic anemia (AA) state has not been reported yet.展开更多
Objective At present,a number of very severe aplastic anemia(VSAA)patients cannot receive hematopoietic stem cell transplantation(HSCT)or standard immunosuppressive therapy(IST)due to the high cost of therapy,shortage...Objective At present,a number of very severe aplastic anemia(VSAA)patients cannot receive hematopoietic stem cell transplantation(HSCT)or standard immunosuppressive therapy(IST)due to the high cost of therapy,shortage of sibling donors,and lack of resources to support the HSCT.In addition,some VSAA patients with autoantibodies have no life-threatening infections or bleeding at the time of initial diagnosis.Considering the disease condition,economics and other factors,the present study designed a new and relatively mild treatment strategy:cyclosporine A plus pulsed high-dose prednisone(CsA+HDP).Methods The present study retrospectively analyzed 11 VSAA patients,who were treated with CsA+HDP in our hospital from August 2017 to August 2019.Results The median follow-up time for these patients was 24.9 months.The overall response rate was 54.5%(6/11)at six months after the initiation of IST and 81.8%(9/11)at deadline.Five patients achieved complete remission and four patients met the criteria for partial response at the last follow-up.The median time to response for responders was 110 days.Three patients underwent HSCT due to the poor effect of CsA+HDP or to find a suitable transplant donor.Recurrence and clonal evolution were not found in any of these patients.The estimated 3-year overall survival rate and 3-year failure-free survival rate were 100.0%and 72.7%,respectively.In addition,the results revealed that the cyclosporine-prednisone-associated toxicity was mild and well-tolerated by most patients.Conclusion The novel CsA+HDP regimen has good therapeutic effect and safety for VSAA patients with autoantibodies,who have no serious life-threatening infections or bleeding at the time of initial diagnosis.展开更多
基金Supported by the Specialized Scientific Research Fund Projects of the Medical Group of Qingdao University,No.YLJT20201002。
文摘BACKGROUND Patients with severe aplastic anemia(SAA)frequently present with inflammatory episodes,and during flared inflammatory episodes,hematopoietic function is further exacerbated.The gastrointestinal tract is the most common site for infectious and inflammatory diseases,and its structural and functional features confer on it the most potent capacity to affect hematopoietic and immune functions.Computed tomography(CT)is a readily accessible approach to provide highly useful information in detecting morphological changes and guiding further work-ups.AIM To explore CT imaging presentations of gut inflammatory damage in adult SAA patients during inflammatory episodes.METHODS We retrospectively evaluated the abdominal CT imaging presentations of 17hospitalized adult patients with SAA in search of the inflammatory niche when they presented with systemic inflammatory stress and exacerbated hematopoietic function.In this descriptive manuscript,the characteristic images that suggested the presence of gastrointestinal inflammatory damage and related imaging presentations of individual patients were enumerated,analyzed and described.RESULTS All eligible patients with SAA had CT imaging abnormalities that suggested the presence of an impaired intestinal barrier and increased epithelial permeability.The inflammatory damages were concurrently present in the small intestine,the ileocecal region and the large intestines.Some readily identified imaging signs,such as bowel wall thickening with mural stratification(“water holo sign”,“fat holo sign”,intramural gas and subserosal pneumatosis)and mesenteric fat proliferation(fat stranding and“creeping fat sign”),fibrotic bowel wall thickening,“balloon sign”,rugged colonic configuration,heterogeneity in the bowel wall texture,and adhered and clustered small bowel loop(including various patterns of“abdominal cocoon”),occurred at a high incidence,which suggested that the damaged gastrointestinal tract is a common inflammatory niche responsible for the systemic inflammatory stresses and the exacerbated hematopoietic failure in patients with SAA.Particularly,the“fat holo sign”was present in 7 patients,a rugged colonic configuration was present in 10 patients,the adhesive bowel loop was present in 15 patients,and extraintestinal manifestations suggestive of tuberculosis infections were present in 5 patients.According to the imaging features,a suggestive diagnosis of Crohn’s disease was made in 5patients,ulcerative colitis in 1 patient,chronic periappendiceal abscess in 1 patient,and tuberculosis infection in 5 patients.Other patients were diagnosed with chronic enteroclolitis with acutely aggravated inflammatory damage.CONCLUSION Patients with SAA had CT imaging patterns that suggested the presence of active chronic inflammatory conditions and aggravated inflammatory damage during flared inflammatory episodes.
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.
文摘BACKGROUND Accumulating evidence demonstrates that autoimmune hematopoietic failure and myeloid neoplasms have an intrinsic relationship with regard to clonal hematopoiesis and disease evolution.In approximately 10%-15%of patients with severe aplastic anemia(SAA),the disease phenotype is transformed into myeloid neoplasms following antithymocyte globulin plus cyclosporine-based immunosuppressive therapy.In some of these patients,myeloid neoplasms appear during or shortly after immunosuppressive therapy.Leukemic transformation in SAA patients during anti-tuberculosis treatment has not been reported.CASE SUMMARY A middle-aged Chinese female had a 6-year history of non-SAA and a 2-year history of paroxysmal nocturnal hemoglobinuria(PNH).With aggravation of systemic inflammatory symptoms,severe pancytopenia developed,and her hemoglobinuria disappeared.Laboratory findings in cytological,immunological and cytogenetic analyses of bone marrow samples met the diagnostic criteria for“SAA.”Definitive diagnosis of disseminated tuberculosis was made in the search for infectious niches.Remarkable improvement in hematological parameters was achieved within 1 mo of anti-tuberculosis treatment,and complete hematological remission was achieved within 4 mo of treatment.Frustratingly,the hematological response lasted for only 3 mo,and pancytopenia reemerged.At this time,cytological findings(increased bone marrow cellularity and an increased percentage of myeloblasts that accounted for 16.0%of all nucleated hematopoietic cells),immunological findings(increased percentage of cluster of differentiation 34+cells that accounted for 12.28%of all nucleated hematopoietic cells)and molecular biological findings(identification of somatic mutations in nucleophosmin-1 and casitas B-lineage lymphoma genes)revealed that“SAA”had transformed into acute myeloid leukemia with mutated nucleophosmin-1.The transformation process suggested that the leukemic clones were preexistent but were suppressed in the PNH and SAA stages,as development of symptomatic myeloid neoplasm through acquisition and accumulation of novel oncogenic mutations is unlikely in an interval of only 7 mo.Aggravation of inflammatory stressors due to disseminated tuberculosis likely contributed to the repression of normal and leukemic hematopoiesis,and the relief of inflammatory stressors due to anti-tuberculosis treatment contributed to penetration of neoplastic hematopoiesis.The concealed leukemic clones in the SAA and PNH stages raise the possibility of an inflammatory stress-fueled antileukemic mechanism.CONCLUSION Aggravated inflammatory stressors can repress normal and leukemic hematopoiesis,and relieved inflammatory stressors can facilitate penetration of neoplastic hematopoiesis.
文摘BACKGROUND Immunosuppressive therapy and matched sibling donor hematopoietic stem cell transplantation(MSD-HSCT)are the preferred treatments for aplastic anemia(AA).CASE SUMMARY In this report,we describe a 43-year-old male patient with severe AA who carried BRIP1(also known as FANCJ),TINF2,and TCIRG1 mutations.Screening of the family pedigree revealed the same TINF2 mutation in his mother and older brother,with his older brother also carrying the BRIP1 variant and demonstrating normal telomere length and hematopoietic function.The patient was successfully treated with oral cyclosporine A,eltrombopag,and acetylcysteine,achieving remission 4 years after receiving MSD-HSCT from his older brother.CONCLUSION This case provides a valuable clinical reference for individuals with suspected pathogenic gene mutations,normal telomere length,and hematopoietic function,highlighting them as potential donors for patients with AA.
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 caused by malignant proliferation and ineffective hematopoiesis.Oncogenic somatic mutations and increased apoptosis,necroptosis and pyroptosis lead to the accumulation of earlier hematopoietic progenitors and impaired productivity of mature blood cells.An increased percentage of myeloblasts and the presence of unfavorable somatic mutations are signs of leukemic hematopoiesis and indicators of entrance into an advanced stage.Bone marrow cellularity and myeloblasts usually increase with disease progression.However,aplastic crisis occasionally occurs in advanced MDS.CASE SUMMARY A 72-year-old male patient was definitively diagnosed with MDS with excess blasts-1(MDS-EB-1)based on an increase in the percentages of myeloblasts and cluster of differentiation(CD)34+hematopoietic progenitors and the identification of myeloid neoplasm-associated somatic mutations in bone marrow samples.The patient was treated with hypomethylation therapy and was able to maintain a steady disease state for 2 years.In the treatment process,the advanced MDS patient experienced an episode of progressive pancytopenia and bone marrow aplasia.During the aplastic crisis,the bone marrow was infiltrated with sparsely distributed atypical lymphocytes.Surprisingly,the leukemic cells disappeared.Immunological analysis revealed that the atypical lymphocytes expressed a high frequency of CD3,CD5,CD8,CD16,CD56 and CD57,suggesting the activation of autoimmune cytotoxic T-lymphocytes and natural killer(NK)/NKT cells that suppressed both normal and leukemic hematopoiesis.Elevated serum levels of inflammatory cytokines,including interleukin(IL)-6,interferon-gamma(IFN-γ)and tumor necrosis factor-alpha(TNF-α),confirmed the deranged type I immune responses.This morphological and immunological signature led to the diagnosis of severe aplastic anemia secondary to large granule lymphocyte leukemia.Disseminated tuberculosis was suspected upon radiological examinations in the search for an inflammatory niche.Antituberculosis treatment led to reversion of the aplastic crisis,disappearance of the atypical lymphocytes,increased marrow cellularity and 2 mo of hematological remission,providing strong evidence that disseminated tuberculosis was responsible for the development of the aplastic crisis,the regression of leukemic cells and the activation of CD56+atypical lymphocytes.Reinstitution of hypomethylation therapy in the following 19 mo allowed the patient to maintain a steady disease state.However,the patient transformed the disease phenotype into acute myeloid leukemia and eventually died of disease progression and an overwhelming infectious episode.CONCLUSION Disseminated tuberculosis can induce CD56+lymphocyte infiltration in the bone marrow and in turn suppress both normal and leukemic hematopoiesis,resulting in the development of aplastic crisis and leukemic cell regression.
文摘Background:To develop a protein-protein interaction network of Paroxysmal nocturnal hemoglobinuria(PNH)and Aplastic anemia(AA)based on genetic genes and to predict pathways underlying the molecular complexes in the network.Methods:In this research,the PNH and AA-related genes were screened through Online Mendelian Inheritance in Man(OMIM).The plugins and Cytoscape were used to search literature and build a protein-protein interaction network.Results:The protein-protein interaction network contains two molecular complexes that are five higher than the correlation integral values.The target genes of this study were obtained:CD59,STAT3,TERC,TNF,AKT1,C5AR1,EPO,IL6,IL10 and so on.We also found that many factors regulate biological behaviors:neutrophils,macrophages,vascular endothelial growth factor,immunoglobulin,interleukin,cytokine receptor,interleukin-6 receptor,tumor necrosis factor,and so on.This research provides a bioinformatics foundation for further explaining the mechanism of common development of both.Conclusion:This indicates that the PNH and AA is a complex process regulated by many cellular pathways and multiple genes.
基金(in part)Instituto de Salud Carlos III(PI11/01907),Ministerio de Economia y Competitividad,co-funded by Fondo Europeo de Desarrollo Regional,Union Europea,Una manera de hacer EuropaRoche Organ Transplantation Research Foundation(ROTRF,CI:442035057)(all to Forns X)
文摘Telaprevir and Boceprevir are the first direct acting antivirals approved for chronic hepatitis C in combination with peg-interferon alfa and ribavirin.Pancytopenia due to myelotoxicity caused by these drugs may occur,but severe hematological abnormalities or aplastic anemia(AA) have not been described.We collected all cases of severe pancytopenia observed during triple therapy with telaprevir in four Spanish centers since approval of the drug in 2011.Among 142 cirrhotic patients receiving treatment,7 cases of severe pancytopenia(5%) were identified and three were consistent with the diagnosis of AA.Mean age was 59 years,five patients had compensated cirrhosis and two patients had severe hepatitis C recurrence after liver transplantation.Severe pancytopenia was diagnosed a median of 10 wk after the initiation of therapy.Three patients had pre-treatment hematological abnormalities related to splenomegaly.In six patients,antiviral treatment was interrupted at the onset of hematological abnormalities.Two patients died due to septic complications and one patient due to acute alveolar hemorrhage.The remaining patients recovered.Severe pancytopenia and especially AA,are not rare during triple therapy with telaprevir in patients with advanced liver disease.Close monitoring is imperative in this setting to promptly detect serious hematological disorders and to prevent further complications.
基金supported by the Specialized Research Fund for the Doctoral Program of Higher Education of China(No.200804871044)
文摘Recent studies indicate that immune-associated aplastic anemia(AA)resembles such autoimmune diseases as insulin-dependent diabetes and chronic autoimmune thyroiditis that belong to organ-specific autoimmune diseases.Many independent investigation groups have successfully isolated the pathopoiesis-associated T cell clone causing hematopoiesis failure with a CD4 phenotype from peripheral blood and bone marrow(BM)in AA patients.In the current study,BM CD4+ T cells were isolated from AA patients and healthy controls with immunomagnetic beads sorting,and proliferation capability,apoptosis features and the impacts of their secreted cytokines on hematopoiesis stem/progenitor cells were compared between them.By 3H-TdR method,CD4+ T cells in AA group presented more enhanced proliferative activity.The stimulation index in control group and AA group was 1.47±0.24,and 2.51±0.34 respectively(P<0.01).After BM CD4+ T cells were induced by high concentration of CD3 monoclonal antibody for 18 h,evident apoptosis cells could be seen under the electron microscope in both control group and AA group.Flow cytometry revealed that apoptosis rates in the early and late stages of AA group were significantly higher than in control group(P<0.01).Early-stage apoptosis rate in control and AA groups was(6.85±1.48)% and(16.98±4.40)%,and late-stage apoptosis rate in control group and AA group was(2.65±1.57)% and(7.74±0.83)%,respectively(P<0.01).The CFU-GM count in AA group and control group was(74.50±9.50)/104 cells and(124.25±19.80)/104 cells respectively under an inverted microscope(P<0.01),and the expression levels of CyclinD3 mRNA and protein in cord blood CD34+ cells were both down-regulated induced by BM CD4+ T cell culture supernatant in AA patients.These results indicate that BM CD4+ T cells of AA patients are likely in an abnormally proliferative,and activated state which can correlate intimately with AA hematopoiesis damage.BM CD4+ T cells in AA patients can secret some soluble cytokines that can inhibit proliferation of hematopoietic stem cells by suppressing the expression of Cyclin D3,resulting in hematopoiesis failure.
基金Supported by National Center for Advancing Translational Sciences,National Institutes of Health,through Grant Nos.UL1TR001436 and 1TL1TR001437(to Broglie L)MACC Fund(to Margolis D and Medin JA)
文摘Acquired aplastic anemia(AA) is a bone marrow failure syndrome characterized by peripheral cytopenias and bone marrow hypoplasia. It is ultimately fatal without treatment, most commonly from infection or hemorrhage. Current treatments focus on suppressing immune-mediated destruction of bone marrow stem cells or replacing hematopoietic stem cells(HSCs) by transplantation. Our incomplete understanding of the pathogenesis of AA has limited development of targeted treatment options. Mesenchymal stem cells(MSCs) play a vital role in HSC proliferation; they also modulate immune responses and maintain an environment supportive of hematopoiesis. Some of the observed clinical manifestations of AA can be explained by mesenchymal dysfunction. MSC infusions have been shown to be safe and may offer new approaches for the treatment of this disorder. Indeed, infusions of MSCs may help suppress auto-reactive, T-cell mediated HSC destruction and help restore an environment that supports hematopoiesis. Small pilot studies using MSCs as monotherapy or as adjuncts to HSC transplantation have been attempted as treatments for AA. Here we review the current understanding of the pathogenesis of AA and the function of MSCs, and suggest that MSCs should be a target for further research and clinical trials in this disorder.
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.
文摘The content of 12 trace elements in the hair of 20 aplastic anemia patients was determined and compared with that of normal subjects as control. The results showed that patients with deficiency of yin had a significant decrease in lithium, calcium, strontium, and chromium, those with deficiency of yang had a distinct decrease in zinc magnesium barium, strontium, calcium, and lithium, and those with deficiency of both yin and yang had a general decrease in all the 12 trace elements. Changes in trace element content in hair may serve as a guide to opening up new vistas in the treatment of aplastic anemia on the basis of an overall analysis of symptoms and signs.
文摘BACKGROUND Cumulative evidence suggests that the aberrant immune responses in acquired aplastic anemia(AA) are sustained by active chronic infections in genetically susceptible individuals. Recently, the constant source to trigger and sustain the pathophysiology has been proposed to come from the altered gut microbiota and chronic intestinal inflammation. In this case, our serendipitous finding provides convincing evidence that the persistently dysregulated autoimmunity may be generated, at least in a significant proposition of AA patients, by the altered gut microbiota and compromised intestinal epithelium.CASE SUMMARY A 30-year-old Chinese male patient with refractory severe AA experienced a 3-month-long febrile episode, and his fever was refractory to many kinds of injected broad-spectrum antibiotics. When presenting with abdominal cramps, he was prescribed oral mannitol and gentamycin to get rid of the gut infection. This treatment resulted in a quick resolution of the fever. Unanticipatedly, it also produced an excellent hematological response. He had undergone three episodes of recurrence within the one-year treatment, with each recurrence occurring 7-8 wk from the gastrointestinal inflammation eliminating preparations. However,subsequent treatments were able to produce subsequent remissions and consecutive treatments were successful in achieving durative hematological improvements, strongly indicating an etiological association between chronic gut inflammation and the development of AA. Interestingly, comorbid diseases superimposed on this patient(namely, psychiatric disorders, hypertension,insulin resistance, and renal dysfunction) were ameliorated together with the hematological improvements.CONCLUSION Chronic gut inflammation may be responsible for AA pathogenesis. The comorbidities and AA may share a common etiological association.
文摘Rationale:Trichosporon,an anamorphic fungus,proliferates under high humidity,causing serious opportunistic infections collectively called trichosporonosis.Among the Trichosporon species causing trichosporonosis are Trichosporon(T.)asahii,T.asteroides,T.cutaneum etc.Patient concerns:A 38-year-old Chinese male with severe aplastic anemia was admitted due to multiple joints pain,poor appetite,and right ankle swelling.One year earlier he had undergone allogeneic hematopoietic stem cell transplantation.Diagnosis:T.asahii infection and severe aplastic anemia.Interventions:Combined treatment of amphotericin B liposomes(55 mg/24 h)and voriconazole(200 mg/12 h)for 8 days.Outcomes:The symptoms of the patient’s ankle were relieved and effusion cultures showed no T.asahii.Lessons:To the best of our knowledge,T.asahii ankle cavity effusion infections are rare.Trichosporon infections may be attributed to risk factors such as improper long-term use of antimicrobials for an underlying disease(e.g.,anemia,hypoalbuminemia).Attention should be paid to prevent and control Trichosporon infections in order to avoid comorbidities.
文摘A transjugular intrahepatic portal-systemic shunt (TIPS) is a standard way to decompress the portal system in cirrhotic patients as a bridge to orthotopic liver transplantation (OLT). Traditionally, TIPS has been indicated for certain portal hypertensive sequelae such as refractory ascites, varices treatment and even hepato-hydrothorax. Herein is a case report on the efficacy of TIPS in an OLT ineligible patient with primary biliary cirrhosis and aplastic anemia who had developed refractive ascites requiring serial paracentesis and esophageal varices. He survived 2.5 years post-TIPS placement and died from complications related to severe leucopenia and the development of sepsis.
文摘Chimeric antigen receptor(CAR)T-cell therapy is an effective new treatment strategy for hematologic malignancies.The success of CAR T-cell therapy in treating leukemia and lymphoma has promoted its development for multiple myeloma(MM),and the initial results of CAR T cell therapy have been encouraging.CAR T-cell therapy target antigens that have been clinically evaluated in MM;these antigens include CD19,B cell maturation antigen(BCMA),CD38,and CD138.A barrier to the widespread use of CAR T-cell therapy is its toxicity,primarily cytokine release syndrome(CRS),and neurologic toxicity.This study reports a patient with refractory MM who also developed megakaryocyte aplastic thrombocytopenia after receiving CAR T-cell therapy;such a case or the unusual side effects involving medications are yet unreported.There are risks in using cyclosporine and other immunosuppressants that may lead to MM recurrence as the use of such substances is contradictory to previous treatments;therefore,we temporarily administered platelet infusion as supportive care.Thus far,the condition of the patient has been steady and the patient regularly takes blood test in the hospital.
基金This study was supported by the National Natural Science Foundation of China(No.81202839)the National Natural Science Foundation of China(No.81774080)+1 种基金the“Taishan Scholar”Project Special Fund(tsqn201812145)the Study Abroad Funding by the People’s Government of Shandong Province and the Affiliated Hospital of Shandong University of Traditional Chinese Medicine.
文摘Objective:To reduce the potential risk in aplastic anemia patients complicated with Gilbert syndrome,and find an effective treatment for the unconjugated hyperbilirubinemia.Material and Methods:The mutation of UGT1A1 gene was identified first via sequencing in patients with Gilbert syndrome complicated by aplastic anemia.Before the treatment for aplastic anemia,bilirubin and phenobarbitone tests were conducted.Patients were then treated for their primary disease and given ursodeoxycholic acid(UDCA)either with or without phenobarbitone.Results:The clinical practice of UDCA,which can alleviate increased bilirubin levels,did not affect the key treatments for aplastic anemia.Conclusions:These results indicate that Gilbert syndrome should be addressed when treating aplastic anemia.Furthermore,abnormal bilirubin levels can be controlled effectively by the UDCA treatment.
文摘IL-2 production and IL-2 receptor (Tac antigen) of the peripheral blood mononuclear cells in 30 patients with aplastic anemic (AA) were studied. We found that mononuclear cells from patients produce spontaneously IL-2 in the absence of exogenous lee-tin stimulation, the proportion of Tac+ cells in mononuclear cells increased. The release of IL-2 and or Tac antigen expression were elevated in almost every patient with AA. The plasma from patients stimulate mitogen-induced blastogenesis and Tac antigen expression of normal human lymphocytes. Immunological 1 abnormalities of patients with AA possibly might represents secondary response to bone marrow depression.
文摘Accelerating cell growth is one of the functions of thyroid hormone. In the absence or lack of this hormone, hematopoietic disorder may occur. Dynamic observation of thyroid function in aplastic anemia (AA) state has not been reported yet.
基金This work was supported by a grant from the National Natural Science Foundation of China(No.21906061).
文摘Objective At present,a number of very severe aplastic anemia(VSAA)patients cannot receive hematopoietic stem cell transplantation(HSCT)or standard immunosuppressive therapy(IST)due to the high cost of therapy,shortage of sibling donors,and lack of resources to support the HSCT.In addition,some VSAA patients with autoantibodies have no life-threatening infections or bleeding at the time of initial diagnosis.Considering the disease condition,economics and other factors,the present study designed a new and relatively mild treatment strategy:cyclosporine A plus pulsed high-dose prednisone(CsA+HDP).Methods The present study retrospectively analyzed 11 VSAA patients,who were treated with CsA+HDP in our hospital from August 2017 to August 2019.Results The median follow-up time for these patients was 24.9 months.The overall response rate was 54.5%(6/11)at six months after the initiation of IST and 81.8%(9/11)at deadline.Five patients achieved complete remission and four patients met the criteria for partial response at the last follow-up.The median time to response for responders was 110 days.Three patients underwent HSCT due to the poor effect of CsA+HDP or to find a suitable transplant donor.Recurrence and clonal evolution were not found in any of these patients.The estimated 3-year overall survival rate and 3-year failure-free survival rate were 100.0%and 72.7%,respectively.In addition,the results revealed that the cyclosporine-prednisone-associated toxicity was mild and well-tolerated by most patients.Conclusion The novel CsA+HDP regimen has good therapeutic effect and safety for VSAA patients with autoantibodies,who have no serious life-threatening infections or bleeding at the time of initial diagnosis.
