Bowel inflammatory presentations on computed tomography in adult patients with severe aplastic anemia during flared inflammatory episodes

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.

Aplastic anemia and severe pancytopenia during treatment with peg-interferon,ribavirin and telaprevir for chronic hepatitis C

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.

Excellent response of severe aplastic anemia to treatment of gut inflammation: A case report and review of the literature

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.

Trichosporon asahii ankle cavity effusion infection in a patient with severe aplastic anemia

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.

A New Immunosuppressive Therapy for Very Severe Aplastic Anemia in Children with Autoantibodies

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.

Haploidentical Allogeneic Hematopoietic Stem Cell Transplantation for Thymoma-associated Severe Aplastic Anemia: a Case Report

THYMOMA,a relatively rare epithelial neoplasm with unique clinical and pathologic features,is the most usual diagnosis for a mass located in the mediastinum.It is often associated with autoimmune disorders.The myasthenia gravis and pure red cell aplasia are the most common disorders,with the incidences of 40%and 5%,respectively,while the incidence of aplastic anemia is only about 0-1.4%.1Thymectomy is hard to perform on patients with severe aplastic anemia

Three Times Spontaneous Remission of Severe Aplastic Anemia Following Granulocyte Transfusion from Related Donors:a Case Report and Literature Review

APLASTIC anemia(AA) is a bone marrow failure disease caused by abnormal activation of T lymphocytes,resulting in the apoptosis of hematopoietic cells and bone marrow failure.1 Currently,hematopoietic stem cell transplantation(HSCT),immunosuppressive therapy(IST),and supportive care(e.g.transfusion adjuvant therapy,hematopoietic

Predictive value of T cell receptor repertoire profiling for immunosuppressive therapy in severe aplastic anemia

Increasing evidence supports the hypothesis of autologous immune attack in severe aplastic anemia(SAA):the predominant role of activated cytotoxic T cells(CTL)expressing-interferon in inhibiting the growth of bone marrow(BM)cells,putative autoantigens,and oligoclonal expansion of CD8+T cells.1 For SAA patients,the definitive therapies are immunosuppressive therapy(IST)or hematopoietic stem transplantation(HSCT).

Prevalence of Severe Anemia (Hb ≤ 5 g/dl) in Non-Dialyzed Chronic Renal Failure Patients in the Nephrology and Hemodialysis Department of Point G University Hospital

Introduction: Chronic renal failure (CRF) is defined as glomerular filtration rate (GFR) less than 60 ml/min/1.73m2 for at least three (3) months. Anemia is one of its most common complications. Anemia increases the risk factor for cardiovascular mortality by 18% per gram of hemoglobin loss. Objectives: To determine the prevalence and characteristics of this severe anemia, to determine the indications for transfusion, the complications related to this anemia, the evolution and the prognosis of these patients. Materials and Methods: This was a descriptive study with retrospective data collection over 18 months (January 1, 2017 to June 30, 2018) that included hospitalized CRF patients. Were included, non-dialyzed chronic renal failure patients with Hb ≤ 5 g/dl hospitalized during the said period. Not included were chronic renal failure patients with an Hb level ≥ 5 g/dl, those followed up and/or hospitalized outside the study period. Results: Among 1176 patients, 26 had severe anemia (Hb level ≤ 5 g/dl) on CRF, a prevalence of 2.21%. The mean age was 40 years ± 32.62 with extremes of 15 and 67 years. Seventeen women and 9 men. The etiology of chronic renal failure (CRF) was hypertensive vascular nephropathy in 50% of cases. CRF was end-stage in 18 patients (69.2%). The mean hemoglobin level was 4.10 g/dl ± 0.64 with extremes of 2 and 5 g/dl. The anemia was microcytic hypochromic in 50% and aregenerative (96.2%). The main symptoms were asthenia in 20 cases (76.9%), dizziness in 20 cases (76.9%), exertional dyspnea in 19 cases (73.1%). Signs of cardiac decompensation (n = 12) were jugular turgor 10 cases (38.5%), hepato-jugular reflux 06 cases (23.1%), mitral insufficiency murmur 06 cases (23.1%). The main complication was left ventricular hypertrophy 17 cases (77.3%). There was no correlation between anemia and sex (p = 0.291), age (p = 0.778), malaria (p = 0.158), etiology of CRF (p = 0.26). The evolution after treatment of anemia was favorable in 19 patients (73.1%), unfavorable in 02 patients (7.7%) and 05 deaths (19.2%). The deaths were of cardiovascular cause: left ventricular insufficiency 04 cases, stroke 01 case. Conclusion: Anemia is frequent in patients with chronic renal failure and remains an important risk factor for cardiovascular disease and poor general condition.

Impact of Anemia on Mortality and Nutritional Recovery among Hospitalized Severely Malnourished Children in Burkina Faso

This study aimed to analyze the impact of anemia on mortality rate and nutritional recovery, during severely malnourished inpatient treatment. Material and Methods: This was a retrospective cohort study conducted from data of severely malnourished children hospitalized at a feeding the rapeutic center. Pearson’s Chi square test, General linear model, Mortality relatives risks, Kaplan-Meir survival curves have been used. Results: At admission, 85.3% of included malnourished children had anemia (Hb ≤ 11 g/dl) and 10.6% severe anemic (Hb 6 g/dl). Mortality rate did not differed significantly from severely malnourished children with anemia (12.4%) and without anemia (22.2%), p = 0.12. Kaplan Meir survival curves did not differed significantly between the two groups, (p Log Rank = 0.11). From admission to discharge, anthropometric Z-scores means evolution did not differed significantly between severely malnourished children with and without anemia at admission. But anthropometric Z-scores means evolution differed significantly within each group’s subjects: WHZ (between groups: p = 0.74;within subjects: p 0.001), and WAZ (between groups: p = 0.54;within subjects: p 0.001). Conclusion: With a strong respect of current recommendation of anemia treatment of inpatient severely malnutrition management, there is no increased mortality rate in SAM anemic group;and nutritional recovery is significant within subjects of SAM anemic and non anemic children, without difference between groups.

Effect of ginsenoside Rg1 on hematopoietic stem cells in treating aplastic anemia in mice via MAPK pathway

BACKGROUND Aplastic anemia(AA)presents a significant clinical challenge as a life-threatening condition due to failure to produce essential blood cells,with the current the-rapeutic options being notably limited.AIM To assess the therapeutic potential of ginsenoside Rg1 on AA,specifically its protective effects,while elucidating the mechanism at play.METHODS We employed a model of myelosuppression induced by cyclophosphamide(CTX)in C57 mice,followed by administration of ginsenoside Rg1 over 13 d.The invest-igation included examining the bone marrow,thymus and spleen for pathological changes via hematoxylin-eosin staining.Moreover,orbital blood of mice was collected for blood routine examinations.Flow cytometry was employed to identify the impact of ginsenoside Rg1 on cell apoptosis and cycle in the bone marrow of AA mice.Additionally,the study further evaluated cytokine levels with enzyme-linked immunosorbent assay and analyzed the expression of key proteins in the MAPK signaling pathway via western blot.RESULTS Administration of CTX led to significant damage to the bone marrow’s structural integrity and a reduction in hematopoietic cells,establishing a model of AA.Ginsenoside Rg1 successfully reversed hematopoietic dysfunction in AA mice.In comparison to the AA group,ginsenoside Rg1 provided relief by reducing the induction of cell apoptosis and inflammation factors caused by CTX.Furthermore,it helped alleviate the blockade in the cell cycle.Treatment with ginsenoside Rg1 significantly alleviated myelosuppression in mice by inhibiting the MAPK signaling pathway.CONCLUSION This study suggested that ginsenoside Rg1 addresses AA by alleviating myelosuppression,primarily through modulating the MAPK signaling pathway,which paves the way for a novel therapeutic strategy in treating AA,highlighting the potential of ginsenoside Rg1 as a beneficial intervention.

An investigation of long-term outcome of rabbit anti-thymocyte globulin and cyclosporine therapy for pediatric severe aplastic anemia

Children with severe aplastic anemia(SAA)face heterogeneous prognoses after immunosuppressive therapy(IST).There are few models that can predict the long-term outcomes of IST for these patients.The objective of this paper is to develop a more effective prediction model for SAA prognosis based on clinical electronic medical records from 203 children with newly diagnosed SAA.In the early stage,a novel model for long-term outcomes of SAA patients with IST was developed using machine-learning techniques.Among the indicators related to long-term efficacy,white blood cell count,lymphocyte count,absolute reticulocyte count,lymphocyte ratio in bone-marrow smears,C-reactive protein,and the level of IL-6,IL-8 and vitamin B12 in the early stage are strongly correlated with long-term efficacy(P<.05).Taken together,we analyzed the long-term outcomes of rabbit antithymocyte globulin and cyclosporine therapy for children with SAA through machine-learning techniques,which may shorten the observation period of therapeutic effects and reduce treatment costs and time.

Metagenomic next-generation sequencing of plasma for the identification of bloodstream infectious pathogens in severe aplastic anemia

Objective To analyze the diagnostic value of cellfree plasma metagenomic next-generation sequencing(mNGS)pathogen identification for severe aplastic anemia(SAA)bloodstream infection.Methods From February 2021 to February 2022,mNGS and conventional detection methods(blood culture,etc.)were used to detect 33 samples from 29 consecutive AA patients admitted to the Anemia Diagnosis and Treatment Center of the Hematology Hospital of the Chinese Academy of Medical Sciences to assess the diagnostic consistency of mNGS and conventional detection,as well as the impact on clinical treatment benefits and clinical accuracy.

Characteristics of Severely Anemic Pregnant Women and Perinatal Outcomes in Banfora Regional Hospital, Burkina Faso: An Epidemiological Study

Severe anemia during pregnancy remains an acute maternal health problem in low income countries and its management is a challenge. This study aimed to analyze the characteristics of hospitalized pregnant women with severe anemia and issue of the management in a regional hospital of a low income country. Material and Methods: This was a retrospective descriptive study from January 1, 2007 to December 31, 2008, at a regional hospital maternity. Data of the 283 pregnancy severe anemia cases have been analyzed using usual Pearson’s Chi square test or Fisher’s exact test. Results: Of the 283 women with pregnancy severe anemia, 98% were illiterate, 98% were household women;majority were in the third trimester (64%);41% had no previous delivery;49% did not had antenatal care. There were no statistics association between hemoglobin values stage and gestational age, gravidity and parity. During the hospitalization, from the 283 women with pregnancy severe anemia, deliveries occurred on 22.6%;abortion on 1%. From the 64 deliveries, 45.3% were alive preterm birth, 20.3% preterm stillbirth, 25.0% at term birth and 9.4% at term stillbirth. Between the 45 alive babies, 91% were low birth weight. In global, from the 283 women, mortality rate was 2.8%. Conclusion:?Severe anemia during pregnancy results in maternal mortality, preterm, low birth and stillbirth even between hospitalized women. As most of the pregnancy anemia risk factors are chronic poverty related factors, intervention must be focused on prevention including health pregnant women iron supplementation and adequate nutritional diet promoting at both health facilities and community level.

Analysis of the Prognostic Factors of Very Severe Aplastic Anemia Treated with Chinese Kidney-Invigorating Drugs in Combination with Anti-lymphocyte Globulin or Anti-thymocyte Globulin

Objective： To explore the prognostic factors for very severe aplastic anemia （VSAA） patients treated mainly with Chinese Kidney （Shen）-invigorating drugs （CKID） combined with anti-lymphocyte globulin （ALG） or anti-thymocyte globulin （ATG）. Methods： Twenty-seven VSAh. patients were treated with CSID＋ALG/ ATG therapy in conjunction with cyclosporine A, androgen, hemopoietic growth factor, etc. The relationship of the effectiveness and some factors （age of patients, course of illness, blood and bone marrow figures, etc.） were analyzed. Results： In the 25 evaluated VSAA patients who had been followed up for over 1 year, 9 patients （36.0%） were basically cured, 5 （20.0%） remitted, 6 （24.0%） were markedly improved, and 5 （20.0%） were treated in vain, with the total effective rate of treatment being 80.0% （20/25）. Better clinical therapeutic effects were shown in patients newly diagnosed with VSAA, of male sex （P=0.037）, 〉20 years old （P=0.045）, with an illness course ≤ 1 month （,P=0.048）, with peripheral neutrophil count 〉0.1 × 10^9/L （P=0.023）, and with reticulocyte count 〉10 × 10^9/L （P=0.002）. Platelet count （P=0.620） and bone marrow lymphocyte percentage （P=0.736） showed no correlation with the therapeutic effectiveness. Multi-factor analysis by the Kaplan-Meier procedure on the factors influencing survival showed that rather longer survival times occurred in patients 〉 20 years old, with peripheral neutrophil count ≤〈0.1 × 10^9/L, reticulocyte count ≤10 × 10^9/L, and platelet count 〉 10 × 10^9/L （allP=0.0001）. Bone marrow lymphocyte percentage and the initiation time of ALG/ATG application （from onset of the illness） showed no significant influence on patients＇ survival time （P=0.085 and P=0.935, respectively）. Conclusions： CSKD＋ALG/ATG therapy for treatment of VSAA could enhance the current clinical therapeutic effects and elevate patients＇ survival rate. Conditions including male sex, age 〉20 years, illness course ≤1 month, neutrophil count 〉0.1× 10^9/L, and reticulocyte count 〉10 × 10^9/L are the likely effective indices for predicting favorable therapeutic effectiveness in newly diagnosed VSAA patients.

Haploidentical hematopoietic cell transplantation for severe acquired aplastic anemia: a case-control study of post-transplant cyclophosphamide included regimen vs. anti-thymocyte globulin & colony-stimulating factor-based regimen

Dear Editor,Haploidentical allogeneic hematopoietic stem cell transplantation(haplo-HSCT),a curative therapy for severe aplastic anemia(SAA)patients,has been used clinically for decades.Two models,not involving ex vitro T-cell depletion,have been adopted for haplo-HSCT in patients with SAA.The first is referred to as the"Beijing protocol"(Xu et al.,2017),and comprises a conditioning regimen using busulfex(BU),cyclophosphamide(CY).

《Upfront haploidentical transplant for acquired severe aplastic anemia:registry-based comparison with matched related transplant》解读

=本文最初发表于2017年《J Hematol Oncol》杂志上,文章题录为:Xu LP,Jin S,Wang SQ,et al.Uptransplant[J].J Hematol Oncol,2017,10:25。本研究在世界范围内首次报道了对多中心的连续病例进行一线单倍体移植与同期一线同胞全相合移植的疗效比较。共纳入11个移植中心的158例患者,所有进行单倍体移植的患者采用相同的移植方案,结果显示单倍型相合移植作为一线治疗与同期一线同胞全相合移植相比,3年总生存率和无失败生存率相似;多因素分析显示移植前输血量以及移植前患者的一般情况(PS评分)是影响生存的独立危险因素;所以对于具备移植条件的重型再生障碍性贫血患者,尽早采取单倍型相合移植作为一线治疗选择值得进一步研究。

A comparative study of unrelated donor and matched-sibling donor allogeneic hematopoietic stem cell transplantation in children and adolescents with acquired severe aplastic anemia

Objective To evaluate the efficacy of unrelated do-nor allogeneic hematopoietic stem cell transplantation(URD allo-HSCT).for children and adolescents with severe aplastic anemia(SAA).Methods Clinical data of34 SAA children and adolescents undergoing allo-HSCT were retrospectively analyzed from October 2001 to October 2015.According to the source of donor,the

Relationship of Cell Compositions in AIIografts with Outcomes after Haploidentical Transplantation for Acquired Severe Aplastic Anemia： Effects of CD34＋ and CD14＋ Cell Doses

Background： The dose of certain cell types in allografts affects engraftment kinetics and clinical outcomes after allogeneic stem cell transplantation （SCT）. Hence, the present study investigated the association of cell compositions in allografts with outcomes after unmanipulated haploidentical SCT （haplo-SCT） for patients with acquired severe aplastic anemia （SAA）. Methods： A total of 131 patients with SAA who underwent haplo-SCT were retrospectively enrolled. Cell subsets in allografts were determined using flow cytometry. To analyze the association of cellular compositions and outcomes, Mann-Whitney U nonparametric tests were conducted for patient age, sex, weight, human leukocyte antigen mismatched loci, ABO-matched status, patient ABO blood type, donor-recipient sex match, donor-recipient relationship, and each graft component. Multivariate analysis was performed using logistic regression to determine independent influence factors involving dichotomous variables selected from the univariate analysis. Results： A total of 126 patients （97.7%） achieved neutrophil engraftment, and 121 patients （95.7%） achieved platelet engraftment. At 100 days after transplantation, the cumulative incidence of II-IV acute graft-versus-host disease （GVHD） was 32.6%. After a median follow-up of 842 （range： 124-4110） days for surviving patients, the cumulative incidence of total chronic GVHD at 3 years after transplantation was 33.7%. The probability of overall survival at 3 years was 83.0%. Multivariate analysis showed that higher total doses of CD14＋ （P = 0.018） and CD34＋ cells （P 〈 0.001） were associated with a successful platelet engraftment. A successthl platelet was associated with superior survival （P 〈 0.001）. No correlation of other cell components with outcomes was observed. Conclusions： These results provide evidence and explain that higher doses ofCD34＋ and CD 14＋ cells in haploidentical allografts positively affect platelet engraftment, contributing to superior survival for patients with SAA.