OBJECTIVES:Matched sibling donors (MSDs) were preferred for haematopoietic stem cell transplantation (HSCT) in severe aplastic anaemia (AA) when lacking MSDs, unrelated donors (URDs) and haploidentical (Haplo) donor would be considered, but limited by increased graft-versus-host disease (GVHD) and recommended only in experienced centres. This study aimed to compare the efficacy and safety of umbilical cord blood transfusion added URD-HSCT (URD-cord-HSCT) to MSD-HSCT and Haplo-HSCT in AA patients. METHODS:Patients who underwent URD-cord-HSCT (n = 26), MSD-HSCT (n = 26) or Haplo-HSCT (n = 52) were retrospectively enrolled at 1:1:2 ratio between January 2014 and December 2023. Clinical characteristics, treatment responses and survival outcomes were evaluated. RESULTS:No significant differences in neutrophil and platelet engraftment. The three-year overall survival (OS) rates were 88.0% ± 6.5%, 92.1% ± 5.3% and 74.8% ± 6.0% (p = .10), and the event-free survival (EFS) rates were 77.3% ± 9.4%, 92.1% ± 5.3% and 69.0% ± 6.4% (p = .13) in URD-cord-HSCT, MSD-HSCT and Haplo-HSCT groups, respectively. Fully HLA-matched URD-cord-HSCT (MUD-cord-HSCT) demonstrated superior OS (100%) and EFS (85.7% ± 13.2%) compared to Haplo-HSCT (p = .046, p = .049) and single HLA allele-mismatched URD-cord-HSCT (MMUD-cord-HSCT, p = .04, p = .04). The incidence of mixed chimerism (MC) was significantly lower in the URD-cord-HSCT group compared to the MSD-HSCT group (0% vs. 24.48%, p = .01). MUD-cord-HSCT experiences lower grade II-IV acute GVHD comparing with MMUD-cord-HSCT (p = .02) and Haplo-HSCT (p = .048). CONCLUSIONS:MUD-cord-HSCT provides an optimal solution for MC and GVHD, with outcome comparable or even better than those of MSD-HSCT.KEY MESSAGESThe best choice of alternative donor for aplastic anaemia remains a clinical challenge, unrelated donors (URDs) or haploidentical (Haplo) donor?Umbilical cord blood (UCB) transfusion added matched unrelated donor (MUD) haematopoietic stem cell transplantation (HSCT) exert nearly 0% cumulative incidence of mixed chimerism and grade II-IV acute/chronic GVHD;UCB added MUD-HSCT (MUD-cord-HSCT), which exert 100% three-year overall survival (OS) and 85.7% event free survival (EFS), rather than matched sibling donor (MSD)-HSCT, exert superiority in OS and EFS than mismatched URD (MMUD)-HSCT and haploidentical-HSCT.MUD-cord-HSCT provides an optimal solution for MC and GVHD, with outcome comparable or even better than those of MSD-HSCT.

Objectives To evaluate the prognostic value of the Molecular International Prognostic Scoring System (IPSS-M) compared to the Revised International Prognostic Scoring System (IPSS-R) in patients with myelodysplastic neoplasms (MDS) in the Jiangnan region of China.Methods A retrospective multicenter study analyzed data from 113 MDS patients across 10 centers in Jiangnan from 2019 to 2022. Patients were stratified using both IPSS-R and IPSS-M for prognostic comparison.Results Reclassification revealed that 63.7% of patients were shifted from their initial IPSS-R stratifications to IPSS-M categories. Survival analysis indicated significant differences in overall survival (OS) across risk groups, with shorter survival observed in higher-risk and older cohorts. Factors influencing OS included age (≥60), bone marrow blast percentage, IPSS-R chromosomal classification, and gene mutations. Receiver operating characteristic (ROC) analysis yielded areas under the curve (AUC) of 0.629 for IPSS-R and 0.705 for IPSS-M.Discussion This study reinforces the utility of IPSS-M for MDS prognosis, particularly in older patients, while acknowledging limitations such as a modest case number and variability in genetic testing methods.Conclusion IPSS-M demonstrates enhanced prognostic capability over IPSS-R for MDS patients, necessitating further validation in larger cohorts.

OBJECTIVE:To investigate the effect of Shisiwei Jianzhong decoction (, SJD) on non-severe aplastic anemia (NSAA). METHODS:Bone marrow mesenchymal stem cells (BMSCs) were isolated from bone marrow samples of 15 NSAA patients and 3 healthy controls. Cells were treated with gradient concentrations of SJD, and a portion was transfected with a vector overexpressing the nuclear factor of activated T cells, cytoplasmic 4 (NFATC4). Cell viability and apoptosis were detected by cell counting kit-8 and flow cytometry, respectively. After adipogenic differentiation induction, lipid droplet formation in BMSCs was examined by Oil Red O staining. The expression of NFATC4, peroxisome proliferator-activated receptor gamma (PPARG), fatty acid-binding protein 4 (FABP4), peroxisome proliferator-activated receptor-gamma coactivator (PGC-1α), and acetylated PGC-1α was measured by quantitative real-time polymerase chain reaction or Western blot. RESULTS:SJD significantly increased the viability and decreased the apoptosis of NSAA-derived BMSCs. It also dose-dependently inhibited lipid droplet formation and decreased the expression of PPARG and FABP4 in NSAA-derived BMSCs. NFATC4 expression was higher in patients with NSAA than in healthy controls, and SJD downregulated its expression. NFATC4 overexpression reversed the inhibitory effect of SJD on adipogenic differentiation. Additionally, SJD promoted the deacetylation of PGC-1α in NSAA-derived BMSCs, which was also partially eliminated by NFATC4 overexpression. CONCLUSIONS:SJD inhibits adipogenic differentiation of BMSCs through downregulating NFATC4, thereby contributing to the remission of NSAA.

Aplastic anemia (AA) is a bone marrow failure syndrome caused by aberrant immune responses and is associated with high mortality and poor prognosis, particularly in patients with severe AA (SAA) or transfusion dependent non severe AA (TD-NSAA). Allogeneic hematopoietic stem cell transplantation (allo-HSCT) has been increasingly adopted in the treatment of AA and has yielded encouraging results. However, fewer than 30% of patients requiring allo-HSCT are able to identify a suitable matched sibling donor (MSD), thereby limiting the broader application of MSD-HSCT. In such cases, alternative donor sources, including matched unrelated donor (MUD) and haploidentical donor (HID), are considered viable options. While there has been reported a higher frequency of chronic graft-versus-host disease (GVHD) with MUD-HSCT and increased rates of poor graft function in haploidentical HSCT (Haplo-HSCT). Additionally, specific human leukocyte antigen (HLA) mismatches in MUD-HSCT have been implicated in heightened risks of severe acute GVHD and mortality. Thus, further clinical practice is required to optimize the strategy. Umbilical cord blood (UCB) has been shown to decrease mixed chimerism (MC) and relapse rates, enhancing the success of combination transplantation strategies. Based on this rationale, our center implemented a novel approach combining UCB transfusion with MUD-HSCT (MUD-cord-HSCT), a strategy that has received limited investigation both domestically and internationally. In this retrospective analysis, we compared the outcomes of MUD-cord-HSCT, MSD-HSCT, and Haplo-HSCT to identify a more effective and safer strategy. This study was approved by the Ethics Committee of the First Affiliated Hospital of Zhejiang Chinese Medical University (2024-KLS-706-01) and was registered at chictr.org.cn under #ChiCTR2500097159. The date of AA patients who received HSCT at the First Affiliated Hospital of Zhejiang Chinese Medical University from January 2014 to December 2023 were retrospectively reviewed. All MUD-cord-HSCT patients were included, and patients who underwent MSD-HSCT or Haplo-HSCT were matched in a 1:1:2 ratio. All patients in the study received the FCA conditioning regimen, consisting of fludarabine (total dose of 150 mg/m²), cyclophosphamide (total dose of 120–200 mg/kg), and rabbit anti-human thymocyte globulin (total dose of 8–10 mg/kg). In the MUD-cord-HSCT group, UCB stem cells were infused on day 01, and peripheral blood stem cells (PBSCs) were administered on days 02 and 03. Both bone marrow and PBSCs were collected and infused in patients receiving transplants from MSD and HID. A total of 104 patients were assigned to three groups: MUD-cord-HSCT (n = 26), MSD-HSCT (n = 26), and Haplo-HSCT (n = 52). The cohort comprised 54 males and 50 females, with a median age of 29 (range 9–55) years. Of these, 86 patients were diagnosed with SAA and 18 with TD-NSAA. There were no significant differences in median engraftment time, engraftment rate, graft failure rate, or poor graft function among the groups. The 3-year overall survival (OS) rates were 88.0% ± 6.5%, 92.1% ± 5.3%, and 74.8% ± 6.0% (P = 0.10), and the event-free survival (EFS) rates were 77.3% ± 9.4%, 92.1% ± 5.3%, and 69.0% ± 6.4% (P = 0.13) for the MUD-cord-HSCT, MSD-HSCT, and Haplo-HSCT groups, respectively. Fully HLA-matched MUD-cord-HSCT (FM-MUD-cord-HSCT) demonstrated superior OS (100%) and EFS (85.7% ± 13.2%) compared to Haplo-HSCT (P = 0.046, P = 0.049) and single HLA allele-mismatched MUD-cord-HSCT (SM-MUD-cord-HSCT, P = 0.04, P = 0.04). The incidence of MC was significantly lower in the MUD-cord-HSCT group compared to the MSD-HSCT group (0% vs. 24.48%, P = 0.01). FM-MUD-cord-HSCT was associated with a significantly lower rate of grade II–IV acute GVHD compared to SM-MUD-cord-HSCT (P = 0.02) and Haplo-HSCT (P = 0.048), as well as a reduced incidence of bloodstream infections (P = 0.003). Moreover, multivariate Cox regression analysis identified failed or poor engraftment as a significant risk factor for OS, while pulmonary infection emerged as an independent risk factor for EFS. Considering the low incidences of MC, GVHD, and infections, along with favorable survival outcomes, HLA fully matched MUD-cord-HSCT demonstrated comparable efficacy and safety to those of MSD-HSCT. Our study suggests a potential superiority of FM-MUD-cord-HSCT over MSD-HSCT, though this observation requires validation through further clinical investigations.

The aim of this work was to investigate the therapeutic effect of modified Shisiwei Jianzhong Decoction (SJD) on aplastic anemia (AA) and its potential pharmacological mechanism from the perspective of mitophagy. A comprehensive approach combining network pharmacology, mendelian randomization, molecular docking and animal experiments was applied to evaluate the properties of SJD against AA. By integrating multiple databases, it was determined that SJD exerted its therapeutic effect on AA by targeting three key targets [mammalian target of rapamycin (MTOR), poly(ADP-ribose) polymerase 1 (PARP1) and Sirtuin 1 (SIRT1)] through four core compounds (quercetin, resveratrol, genistein and curcumin). Mendelian randomization analysis identified MTOR as a risk factor for AA occurrence while PARP1 was a protective factor. Results of animal experiments showed that SJD improved peripheral blood counts and promoted the proliferation of hematopoietic stem cells. Mechanistically, SJD, especially at high dose, played a therapeutic role in AA by activating mitophagy-related proteins PTEN induced kinase 1 (PINK1)/Parkin and inhibiting the phosphatidylinositol 3-kinase (PI3K)/protein kinase (AKT)/MTOR pathway. This study revealed for the first time the core chemical composition of SJD and its pharmacological effects against AA, which can restore hematopoietic function by activating mitophagy. The results provide inspiration for the clinical application of traditional Chinese medicine in AA treatment.

Introduction: Immunosuppressive therapy (IST) combined with the thrombopoietin receptor agonist (TPO-RA) is the first-line recommendation for patients with severe aplastic anemia (SAA) who are not eligible for hematopoietic stem cell transplantation (HSCT). Hetrombopag, a novel small molecule TPO-RA, has demonstrated promising efficacy in IST-refractory SAA in our previous single-arm phase 2 study (NCT03557099). To further evaluate the efficacy and safety of hetrombopag in combination with standard IST as first-line treatment for untreated SAA patients, we conducted this randomized, double-blind, placebo-controlled phase 3 study (NCT03825744) and reported the results. Methods: Eligible patients aged 15-75 years with untreated SAA according to the Camitta criteria and ineligible for HSCT were enrolled. Patients were randomly assigned in a 2:1 ratio to receive either hetrombopag plus IST (antithymocyte globulin [ATG] and cyclosporine [CsA]) or placebo plus IST. Randomization was stratified based on the source of ATG (rabbit or pig-derived). Hetrombopag or placebo was administered orally on an empty stomach at a daily dose of 15 mg for 6 months. ATG was administered intravenously for 5 consecutive days, and CsA was given orally for 6 months. The primary endpoint was hematologic complete response (CR) rate at 6 months. Results: A total of 240 patients were randomized, with 160 patients in the hetrombopag group and 80 in the placebo group. At 6 months, the CR rate was 28.1% (95% CI 21.2-35.1) in the hetrombopag group and 13.8% (95% CI 6.2-21.3) in the placebo group, indicating a significant between-group difference of 14.4% (95% CI 4.1-24.6, 2-sided p=0.0129). The OR rate at 6 months was 63.8% in the hetrombopag group and 42.5% in the placebo group. At 3 months, the CR rate was 8.8% and 5.0%, and the OR rate was 50.6% and 25.0% in the hetrombopag and placebo group, respectively. The median time to a first hematologic response was 87.0 days (95% CI 86.0-111.0) in the hetrombopag group and 141.0 days (95% CI 113.0-NA) in the placebo group. At 6 months, the proportion of patients who were red-cell transfusion independent was 69.0% in the hetrombopag group and 48.7% in the placebo group, respectively. Platelet transfusion independence was achieved in 69.0% and 50.6% of patients, respectively. At 3 months, the proportions were 56.8% in the hetrombopag group and 27.6% in the placebo group for red-cell transfusion independence, and 54.4% vs 31.2% for platelet transfusion independence, respectively. The incidence of adverse events was comparable between the two groups, with no unexpected safety signals observed for hetrombopag. Grade ≥3 treatment-related adverse events (TRAE) were reported in 15.6% of patients in the hetrombopag group and 19.2% in the placebo group, with serious TRAE reported in 2.5% and 2.6% of patients, respectively. There were no treatment-related deaths reported. The incidence of abnormal hepatic function was 41.9% in the hetrombopag group and 48.7% in the placebo group; 35.0% and 34.6% in each group were considered treatment-related. Additionally, myelodysplastic syndromes were observed in one (0.6%) patient in the hetrombopag group and not reported in the placebo group, while myelofibrosis was reported in 0.6% of patients in the hetrombopag group and 2.6% of patients in the placebo group, respectively. Conclusions: The addition of hetrombopag to IST as first-line treatment for SAA patients led to a significantly higher hematologic response rate. These findings support hetrombopag as an effective and safe therapy for SAA patients ineligible for HSCT. Further studies are necessary to assess the long-term efficacy and safety of this treatment approach.

Abstract Objectives The Revised international prognostic scoring system (IPSS-R) is now commonly being used clinically to guide the treatment of myelodysplastic neoplasms (MDS). Recently, the Molecular International Prognostic Scoring System (IPSS-M)was proposed. In this study, we have validated the potential predictive value of the comparative IPSS-M in Chinese MDS patients. Design Retrospective multicenter observational study. Setting and participants 113 MDS patients(April 2019 - June 2022) from 10 distinct centers in Jiangnan region of China, grouped by IPSS-R and IPSS-M was obtained and the scoring criteria were retrospectively analyzed to compare the prognostic assessment efficacy of the different prognostic assessment systems. Main outcome measures The prognostic indicators of MDS patients are main outcome measures. Results 72 (63.7%) patients were reclassified after regrouping from IPSS-R to IPSS-M, and 52 of them were transferred to a higher risk group, with a higher percentage of patients aged ≥ 60 years in the higher risk group. Survival analysis confirmed that overall survival(OS) was variable in the different risk strata, with shorter survival time in the higher risk group and lower OS in the older(≥ 60 years) than in the younger group; whereas in univariate and multifactorial analysis, age ≥ 60 years, percentage of bone marrow blasts, chromosomal classification of IPSS-R, TP53, RUNX1, DNMT3A, NRAS, CBL, GNAS, and FLT3_ITD gene mutation were associated with OS. Leukemia-free survival(LFS)analysis revealed that higher IPSS-R and IPSS-M risk stratification was linked with shorter LFS time. Receiver operating characteristic (ROC) curves were drawn according to OS displaying AUC = 0.629 for IPSS-R and AUC = 0.705 for IPSS-M; AUC = 0.635 for IPSS-M younger group and AUC = 0.691 for older group. Conclusions Our study confirmed that the IPSS-M prognostic scoring system could be applicable to Chinese patients and that IPSS-M was significantly better than IPSS-R for the prognostic assessment of MDS patients. Moreover, IPSS-M appeared to have better predictive validity in older patients compared to younger patients.

Eltrombopag (EPAG) can improve the efficacy of immunosuppressive therapy (IST) consisting of antithymocyte immunoglobulin (ATG) and cyclosporin in severe aplastic anemia (SAA) patients. This study explored whether patients with SAA could benefit from continuous usage of EPAG beyond 6 months. Seventy-four treatment-naive Chinese patients with SAA were administrated with rabbit ATG-based IST plus EPAG for 6 months. Patients not achieving complete remission (CR) at 6 months were treated with EPAG for another 6 months. At 1, 3, 6 and 12 months after IST, the cumulative response rates were 31

Eltrombopag (EPAG), a thrombopoietin receptor agonist, was approved for the treatment of severe aplastic anemia (SAA) combined with immunosuppressive therapy (IST). However, the effects of real-life use of low doses of EPAG combined with rabbit antithymocyte globulin (ATG)–based IST in Asian patients with SAA are yet unknown. A total of 121 previously untreated Chinese patients with SAA were enrolled in a multicenter registry of the Chinese Eastern Collaboration Group of Anemia (2014–2020): 67 patients received IST alone and 54 patients received additional EPAG. Patients receiving IST plus EPAG had a higher overall response rate (ORR) at 1 month (P = 0.002), 3 months (P = 0.028), 6 months (P = 0.006), and 12 months (P = 0.031) compared to those receiving IST alone. EPAG was the favorable factor for response efficacy at 6 months. The complete response rate in the EPAG plus IST group was 17% at 3 months, 27% at 6 months, and 32% at 12 months, compared to 7% (P = 0.069), 14% (P = 0.11), and 33% (P = 0.92) for those treated with IST alone. The 2-year overall survival rate in EPAG plus IST and IST alone groups was 98% and 88%, respectively (P = 0.078). The rate of adverse events, including clonal evolution, infection, and transaminitis, was similar in the two cohorts. The addition of EPAG to IST was well-tolerated and associated with high rates of hematologic responses among the previously untreated Chinese patients with SAA.

OBJECTIVE:To observe the clinical characteristics and impact on mortality of carbapenem-resistant Pseudomonas aeruginosa (CRPA) colonized or infected patients with hematological disorders in order to provide evidence for the prevention and treatment of CRPA.METHODS:The patients who were colonized or infected with CRPA in the Department of Hematology of The First Affiliated Hospital of Zhejiang Chinese Medical University from January 2020 to March 2021 were selected as the research subjects, the clinical data such as hospitalization time, primary disease treatment regimen, granulocyte count, previous infection and antibiotic regimen of these patients were analyzed, meanwhile, antibiotic regimen and efficacy during CRPA infection, 30-day and long-term survival were also analyzed.RESULTS:A total of 59 patients were included in this study, and divided into CRPA infection group (43 cases) and CRPA colonization group (16 cases). Univariate logistic regression analysis showed that ECOG score (P =0.003), agranulocytosis (P <0.001), and exposure to upper than 3rd generations of cephalosporins and tigecycline within 30 days (P =0.035, P =0.017) were the high-risk factors for CRPA infection. Multivariate logistic regression analysis showed that ECOG score of 3/4 ( OR=10.815, 95%CI: 1.260-92.820, P =0.030) and agranulocytosis ( OR=13.82, 95%CI: 2.243-85.176, P =0.005) were independent risk factors for CRPA infection. There was a statistically significant difference in cumulative survival rate between CRPA colonization group and CRPA infection group ( χ2=14.134, P < 0.001). Kaplan-Meier survival analysis showed that the influencing factors of 30-day survival in patients with CRPA infection were agranulocytosis (P =0.022), soft tissue infection (P =0.03), and time of hospitalization before CRPA infection (P =0.041). Cox regression analysis showed that agranulocytosis was an independent risk factor affecting 30-day survival of patients with CRPA infection (HR=3.229, 95%CI :1.093-3.548, P =0.034).CONCLUSIONS:Patients with hematological disorders have high mortality and poor prognosis after CRPA infection. Bloodstream infection and soft tissue infection are the main causes of death. Patients with high suspicion of CRPA infection and high-risk should be treated as soon as possible.

A retrospective analysis was conducted based on the clinical data from 60 patients older than 16 years from January 2016 to January 2021. All the patients were newly diagnosed with severe aplastic anemia (SAA) with an absolute neutrophil count (ANC) of zero. We compared the hematological response and survival of haploidentical–allogeneic hematopoietic stem cell transplantation (HID-HSCT) (n = 25) and intensive immunosuppressive therapy (IST) (n = 35) treatments. At six months, the overall response rate and complete response were significantly higher in the HID-HSCT group than those in the IST group (84.0

BACKGROUND:Multiple myeloma (MM) is a malignant plasma cell disease. In recent years, several systematic reviews, and meta-analyses have been published on treatment protocols, including autologous stem cell transplantation for MM.METHODS:Web of Science, PubMed, Embase, and Cochrane Library were searched to systematically summarize the quality of the methodology and evidence of meta-analyses regarding treatment of MM including autologous stem cell transplantation.RESULTS:Total 11 meta-analyses were included. The preferred reporting items for systematic reviews and meta-analyses evaluation revealed that the quality of included reviews was affected by possible unevaluated bias between studies and the lack of protocol and registration. The AMSTAR2 scale indicated that the quality of the methodology of included reviews ranged from very low to moderate. The grading, assessment, development, and evaluation of recommendations evaluation showed that among the included outcome indicators, most of them are of low quality.CONCLUSION:This overview suggested that the combination of drugs has improved patient survival rates, efficacy and safety compared with the standard regimen. However, the strength of the evidence is uneven and due to methodological errors, the results should be interpreted with caution in order to provide a reference for further improvement of the study design. The methodological quality of the relevant meta-analysis needs to be further improved.

Addition of eltrombopag (E-PAG) to intensive immunosuppressive therapy (IST) contributes to restoring hematopoiesis in patients with severe aplastic anemia (SAA). Used at relatively low doses in the East Asian population, the efficacies of E-PAG and the predictors for efficacy are not clear. We conducted a retrospective, multicenter study to analyze the efficacy and the possible predicting factors at 6 months in 58 adult SAA patients with rabbit ATG-based IST and E-PAG. The response rate and complete response rate at 6 months were 76% and 21%, respectively. The baseline reticulocyte percentage [area under a curve (AUC)=0.798, 95% confidence interval (CI) 0.640-0.956, P=0.006], absolute reticulocyte count (ARC) (AUC =0.808, 95%CI 0.647-0.970, P=0.004), red cell distribution width – coefficient of variation (RDW-CV) (AUC=0.722, 95%CI 0.494-0.950, P=0.040), and absolute lymphocyte count (ALC) (AUC=0.706, 95%CI 0.522-0.890, P=0.057) were highly predictive of response at 6 months. The tipping values of reticulocyte percentage, ARC, RDW-CV, and ALC were 0.45%, 7.36×109/L, 11.75%, and 1.06×109/L, respectively. The sensitivity and specificity of reticulocyte percentages were 81.6% and 66.7%; ARC were 86.8% and 66.7%, RDW-CV were 94.7% and 55.6%; ALC were 55.3% and 88.9%. At a median follow-up of 15.5 months, the 2-year cumulative overall survival was 92%. The baseline reticulocyte percentage, ARC, RDW-CV, and ALC were potential factors in predicting a favorable effect of rabbit-ATG based IST plus E-PAG in SAA patients of East Asia (ChiCTR2100045895).Clinical Trial Registrationhttp://www.chictr.org.cn/edit.aspx?pid=125480&htm=4, identifier ChiCTR2100045895.

Background:Hematopoietic stem cell transplantation (HSCT) has become the main treatment for acute myeloid leukemia (AML) and has been studied in many systematic reviews (SRs), but strong conclusions have not been drawn yet.Objective:This study aimed to summarize and critically evaluate the methodological and evidence quality of SRs and meta-analysis on this topic.Methods:PubMed, Embase, the Cochrane Library, and Web of Science were searched for SRs/meta-analyses regarding HSCT for AML. Two reviewers assessed the quality of SRs/meta-analyses in line with AMSTAR-2 and evaluated the strength of evidence quality with the grading of the evaluation system (GRADE) for concerned outcomes independently.Results:12 SR/Meta articles were included, and the AMSTAR-2 scale showed that the quality grade of all articles was low or very low. GRADE results showed 29 outcomes, 2 of which were high, 12 were moderate, and 15 were low. Limitations and inconsistency were the most important factors leading to degradation, followed by imprecision and publication bias. Allo-SCT had better OS and DFS benefits than auto-SCT and significantly reduced the relapse in intermediate-risk AML/CR1 patients. Auto-SCT was associated with lower TRM than allo-SCT but generally had higher relapse. The results should be confirmed further for the low or moderate evidence quality.Conclusion:Current SRs show that allo-SCT in the treatment of AML might improve the OS, RFS, and DFS. Auto-SCT has significantly lower TRM but higher RR. Whether bone marrow transplantation is superior to nonmyeloablative chemotherapy remains to be evaluated. Meanwhile, the quality of methodology needs to be further improved. The intensity of evidence was uneven, and the high-quality evidence of outcomes was lacking. Considering the limitations of our overview, more rigorous and scientific studies are needed to fully explore the efficacy of different interventions of HSCT in AML, and clinicians should be more cautious in the treatment.

目的 观察消瘀泄浊饮对慢性环孢素肾病(CCN)患者血管紧张素转化酶2-血管紧张素(1-7)-Mas受体[ACE2-Ang(1-7)-Mas]轴相关组分的干预作用.方法 选取2019年12月至2020年12月再生障碍性贫血(AA)伴CCN患者42例,随机分为对照组和干预组,每组各21例.对照组给予西医治疗,干预组在对照组基础上加用消瘀泄浊饮,治疗8周,比较治疗前后肾功能、ACE2-Ang(1-7)-Mas轴相关组分的变化.结果 干预组治疗后肾功能优于对照组(P<0.01).干预组治疗后ACE2水平高于对照组(P<0.01).对照组治疗后转化生长因子-β(TGF-β)水平明显高于干预组(P<0.05).结论 消瘀泄浊饮通过激活ACE2-Ang(1-7)-Mas轴,改善CCN患者的肾功能,延缓肾间质纤维化.

The outcomes of myelodysplastic syndrome (MDS) patients with SF3B1 mutation, despite identified as a favorable prognostic biomarker, are variable. To comprehend the heterogeneity in clinical characteristics and outcomes, we reviewed 140 MDS patients with SF3B1 mutation in Zhejiang province of China. Seventy-three (52.1%) patients diagnosed as MDS with ring sideroblasts (MDS-RS) following the 2016 World Health Organization (WHO) classification and 118 (84.3%) patients belonged to lower risk following the revised International Prognostic Scoring System (IPSS-R). Although clonal hematopoiesis-associated mutations containing TET2, ASXL1 and DNMT3A were the most frequent co-mutant genes in these patients, RUNX1, EZH2, NF1 and KRAS/NRAS mutations had significant effects on overall survival (OS). Based on that we developed a risk scoring model as IPSS-R×0.4+RUNX1×1.1+EZH2×0.6+RAS×0.9+NF1×1.6. Patients were categorized into two subgroups: low-risk (L-R, score <= 1.4) group and high risk (H-R, score > 1.4) group. The 3-year OS for the L-R and H-R groups was 91.88% (95% CI, 83.27%-100%) and 38.14% (95% CI, 24.08%-60.40%), respectively (P<0.001). This proposed model distinctly outperformed the widely used IPSS-R. In summary, we constructed and validated a personalized prediction model of MDS patients with SF3B1 mutation that can better predict the survival of these patients.

BACKGROUND Hepatitis-associated aplastic anemia (HAAA) is a rare condition. Patients with HAAA usually present with acute hepatitis, jaundice and significantly increased transaminase. After 1-2 mo, hepatitis gradually improves, but progressive hemocytopenia, bone marrow hematopoietic failure, and severe or extremely severe aplastic anemia are manifest. Most cases of HAAA are fulminant and usually lethal if left untreated. The literature on Epstein-Barr virus (EBV)-associated HAAA is sparse. CASE SUMMARY We report a 30-year-old man who was admitted to our hospital because of pale yellow urine and skin with a simultaneous decrease in peripheral blood ternary cells. We made a diagnosis of EBV-associated HAAA. The treatment strategy for this patient included eltrombopag, an immunosuppressive regimen of rabbit anti-human thymocyte immunoglobulin, cyclosporine, and supportive care. The patient was discharged in normal physical condition after five months. A hemogram performed on follow-up revealed that he had achieved a complete response. CONCLUSION Eltrombopag plus anti-thymocyte globubin and cyclosporine may be a therapeutic option for EBV-associated HAAA.Larger studies are warranted to confirm.

BACKGROUND:Icariin, the main pharmacological active flavonoid extracted from Epimedi herba, can regulate cellular processes in diverse diseases. The aim of this study was to explore the effects and mechanisms of icariin on proliferation and adipogenesis of bone marrow mesenchymal stem cells (BMSCs) in aplastic anemia (AA).METHODS AND RESULTS:Bone marrow mesenchymal stem cells were isolated from posterior tibias and femurs of AA rats that were induced by benzene and cyclophosphamide and gavaged with icariin. The isolated BMSCs were characterized morphologically and immunologically by positive markers (CD29 and CD90) and negative markers (CD34 and CD45). CCK-8 assay was performed to examine the BMSCs proliferation. Cell apoptosis and cell cycle were detected by flow cytometry. Oil red O staining was carried out to evaluate the adipogenesis of BMSCs. The mRNA expression of PPARγ, C/EBP-α, and FABP4 was measured by qRT-PCR. The protein levels of p-p38/p38, p-JNK/JNK, p-ERK/ERK, PPARγ, C/EBP-α, and FABP4 were detected using Western blotting. Icariin promoted the proliferation of BMSCs from AA rats in a dose-dependent manner. The protein levels of p-p38/p38, p-JNK/JNK, and p-ERK/ERK were downregulated in BMSCs from AA rats after icariin treatment. Icariin inhibited the apoptosis and arrested cell cycle at G/S phase of BMSCs from AA rats. The adipogenesis of BMSCs from AA rats was also suppressed after icariin treatment. However, the effects of icariin on BMSCs were weakened by p38 agonist addition.CONCLUSIONS:Icariin promoted the proliferation and inhibited the apoptosis and adipogenesis of BMSCs in AA by suppressing MAPK pathway.

肝炎相关再生障碍性贫血属于特殊类型的再生障碍性贫血,典型患者可表现为肝炎后的全血细胞减少.近年来,针对肝炎相关再生障碍性贫血的发病模式和临床特征有了新的认识和发现,疾病的发生更接近"肝炎-再生障碍性贫血综合征"的表现,表现为肝脏细胞和骨髓细胞同时或先后被杀伤性T淋巴细胞所杀伤.临床治疗方案的选择,需要综合考虑患者年龄、疾病严重程度,以及是否有合适供者,以期最大程度提高疗效.

目的:评估环磷酰胺联合泼尼松(CP)方案治疗环孢菌素(CsA)难治/复发的大颗粒淋巴细胞白血病(LGLL)相关纯红细胞再生障碍(PRCA)的疗效及耐受性.方法:回顾性分析登记于中国东部贫血协作组(CEC-GA)数据库的21例CsA治疗无效或复发的LGLL相关PRCA患者临床资料及接受CP方案治疗结果,评估疗效及耐受性.结果:CsA难治/复发患者共21例,其中难治性16例、复发性5例,经CP方案治疗后,15例达完全缓解(CR),3例达部分缓解(PR),3例治疗无效,治疗总有效率为85.7％(18/21),CR率为71.4％(15/21),中位达PR时间为2.2(0.5～6.6)个月,中位达CR时间为2.3(1.3～6.8)个月,中位疗效维持时间17.0(5.0～32.0)个月.8例STAT3突变阳性患者中7例达CR.13例(61.9％)患者在CP方案治疗期间出现不良反应,主要为粒细胞减少和肝功能异常,2例患者因4级粒细胞减少停药.随访期内,无治疗相关死亡事件.3例(14.3％)患者因药物减停出现复发.中位随访20.0(4.0～34.0)个月,15例仍有效,中位无复发生存时间为16.0(3.0～32.0)个月.结论:对于CsA难治/复发的LGLL相关PRCA患者,CP方案疗效确切,且对STAT3突变阳性患者也效果良好.CP方案主要不良反应为骨髓毒性.