Backgroud: Myelodysplastic neoplasms (MDS) are characterized by myelodysplasia and ineffective hematopoiesis leading to refractory cytopenia. Most of MDS patients had anemia at diagnosis requiring red blood cell (RBC) transfusion, which was an independent prognostic factor for poor overall survival of MDS. Therefore, improving anemia is one of the main goals of therapy in LR-MDS patients. Luspatercept, the transforming growth factor-β pathway inhibitor, showed good efficacy in low-risk MDS (LR-MDS) based on clinical trials. Aim: In this study, we analyzed the efficacy and safety of luspatercept in patients with low-blasts MDS (MDS-LB) compared to erythropoiesis-stimulating agents (ESA) in real world. Methods: The study planned to enroll MDS-LB patients newly diagnosed in the Department of Hematology, General Hospital of Tianjin Medical University from June 1st, 2022 to December 30th, 2024. The patients were divided into LR-MDS group (IPSS-R score ≤ 3.5) and HR-MDS group (IPSS-R score > 3.5) based on IPSS-R. The MDS patients in luspatercept group were received luspatercept treatment, as administered subcutaneously every 3 weeks. The starting dose of luspatercept was 1.0 mg per kilogram of body weight (mg/kg). If without erythroid response (HI-E, according to IWG 2018 criteria) and without disease progression after 2 cycles, patients could be received luspatercept with adjustment to a dose of 1.33 mg/kg and then to 1.75 mg/kg. The ESA group were received rhEPO ± roxadustat treatments. The primary end-point was the proportion of patients with HI-E. The key secondary end point was RBC transfusion independence (RBC-TI) for 8 weeks or longer. The adverse events (AE) were defined according to CTCAE 5.0. Results: The data-cutoff was June 30, 2024. A total of 48 MDS-LB were enrolled in this study (Luspatercept group n=27, ESA group n=21).(Table 1) Among luspatercept group, 11 (40.7%) had received treatments combined with ESA (including recombinant human EPO, roxadustat). The results showed that patients treated with luspatercept have a higher HI-E rate than those treated with ESA (73.9% vs. 55%), which might not be affected by SF3B1 mutation, serum erythropoietin level or transfusion burden. After 2 cycles of luspatercept treatment, the median Hb level increased significantly (P<0.05). The patients with first-line treatment, LR-MDS and combined treatments tended to have a higher response rate to luspatercept. The median time to achieve HI-E in luspatercept group was shorter than that of controls (1.5 vs. 5 months, P<0.01). (Table 1, Figure1) There was no serious AE observed. In luspatercept group, the median duration of response (mDOR) of patients received ≥ 3 cycle treatments was higher than that of < 3 cycles group (8 vs. 3 months, P<0.05). (Figure2) The HI-E group tend to have higher population of Treg, and lower concentrations of IL-2, IL-6, TNF-α and IFN-γ compared to non-HI-E group. The serum ferritin (SF), B-type natriuretic peptide (BNP) and C-reactive protein (CRP) levels in HI-E group tended to be lower than that of non-HI-E group. But there was no significant statistical difference between the two groups (all P>0.05). The BNP levels of patients with HI-E after luspatercept treatment were lower than the base-line (P <0.05). (Figure3) It indicated that inflammation factors might affect the response of luspatercept in MDS. Conclusions: This study showed that luspatercept was effective and tolerated well in MDS-LB patients. But inadequate treatments could affect the duration of response. It need to optimize the treatment of luspatercept in further. Key words: MDS-LB, luspatercept, EPO refractory, anemia, immune state

To retrospectively analyze the efficacy and safety of venetoclax combined with azacitidine (VEN + AZA) in the treatment of elderly patients with acute myeloid leukemia. The clinical data for 57 AML patients treated with the VEN + AZA regimen from December 2019 to November 2022 in the Department of Hematology, General Hospital of Tianjin Medical University, were collected. Of the 57 patients included in this study, the mean age of onset was 69.89 (+/- 8.88) years. The median follow-up time was 8.57 months, and the median OS time was 11.50 months. The ORR, CR rate, and MRD (<0.1%) negativity rate were 87.5%, 68.8%, and 58.3%, respectively. The median OS was longer in patients who achieved CR/CRi and who were MRD-negative than in those who did not. MRD negativity was less likely to be achieved in patients aged >= 75 years and with ECOG scores of >= 3. Compared to traditional intensive chemotherapy, MRD negative was achieved more quickly with VEN + AZA regimens in patients with newly diagnosed AML. Advanced age and ECOG score were risk factors for negative MRD. The dominant adverse reactions were hematological adverse events. VEN + AZA regimens in elderly unfit patients with previously untreated newly diagnosed AML have sufficient efficacy and safety.

Objective Immune thrombocytopenia (ITP) is an autoimmune hemorrhagic disease. The immune imbalance of T cells is an essential pathological mechanism of ITP, more specific, the balance of Effector T cells (Teff)/Regulatory T cell (Treg) maintains T cell immune homeostasis. Dendritic cells (DC), the largest antigen-presenting cell, interfere with T cell differentiation pathways and exert immune regulatory functions. Our team created and applied the “ NingXueShengBan” (NXSB) decoction. According to our prior studies, we found that NXSB decoction could restore Th17/Treg balance in ITP mice by regulating protein expression in Notch pathway. Therefore, we further research the mechanism of NXSB decoction that regulates ITP immune homeostasis through affecting the interaction between DC and T cells. Methods In this study, we collected peripheral blood from health donors and ITP patients and extracted DC and CD4 + T cells then grouped in control group, model group and NXSB group. Moreover, we established a co-culture model simulating the immune environment in ITP patient to further investigate whether NXSB had therapeutic effects by the interaction between DC and CD4 + T cells. Results In the current study, we found that NXSB decoction potently regulated interaction between DC and T cells by inhibiting DC development and function, specifically, the differentiation of CD4+ T cells was inhibited after NXSB decoction intervened. Our data showed that NXSB decoction inhibited Toll-like receptor 4 (TLR-4), reduced the expression of Nuclear factor kappa-B (NF-κB) and led to the reduction of downstream inflammatory factors, thereby inhibiting the inflammatory response. More importantly, NXSB decoction reduced the DC surface expression of activation and maturation markers. Moreover, we detected that the decreased expression of the phosphorylated Phosphatidylinositol 3-kinase (PI3 K), Protein kinase B (Akt), Mammalian target of rapamycin (mTOR), and their downstream effectors indicated, we found that NXSB decoction could inhibit PI3 K/Akt/mTOR signaling pathways significantly. Conclusions Collectively, our data suggested that NXSB decoction ameliorates ITP-induced immune imbalance via its anti-inflammation and immunosuppressive by regulating TLR-4/ NF-κB and PI3 K/Akt/mTOR signaling pathways.

目的 观察犀角地黄汤合方含药血清对树突状细胞(DC)激活T细胞增殖分化的影响及其对免疫性血小板减少症(ITP)的作用机制.方法 将10只雄性SD大鼠随机分为含药血清组和空白血清组,每组5只,分别使用犀角地黄汤合方和蒸馏水连续灌胃3 d,腹主动脉取血制备含药血清和空白血清.分选15例健康志愿者及8例ITP患者CD4+T细胞,将荷载血小板抗原的DC与CD4+T细胞共培养,采用随机数字表法分为对照组,模型组,犀角地黄汤合方低、中、高剂量组.对照组为荷载血小板抗原的DC与健康志愿者CD4+T细胞,模型组和犀角地黄汤合方低、中、高剂量组为荷载血小板抗原的DC与ITP患者的CD4+T细胞,其中对照组和模型组加入大鼠空白血清,犀角地黄汤合方低、中、高剂量组分别加入体积分数为5％、10％及20％大鼠含药血清.流式细胞术(FCM)检测CD4+T细胞的增殖情况,各组调节性T细胞(Treg)和效应性T细胞(Teff)的比例以及CD4+T表面程序性死亡受体-1(PD-1)的表达量;酶联免疫吸附试验检测各组细胞上清液中促炎因子白细胞介素(IL)-2、干扰素-γ(IFN-γ)、IL-17以及抑炎因子转化因子-β(TGF-β)、IL-10的表达量.结果 与对照组比较,模型组CD4+T细胞增殖百分比、Teff细胞比例以及促炎因子IL-2、IFN-γ和IL-17升高(P<0.05),Treg细胞比例、CD4+T细胞表面PD-1表达量以及抑炎因子TGF-β、IL-10水平降低(P<0.05);与模型组比较,犀角地黄汤合方低、中、高剂量组CD4+T细胞增殖百分比、Teff细胞比例依次降低,Treg细胞比例、CD4+T细胞表面PD-1表达量和抑炎因子IL-10、TGF-β升高(P<0.05),促炎因子IL-2的量降低(P<0.05);与模型组相比,犀角地黄汤合方中、高剂量组IFN-γ和IL-17降低(P<0.05).结论 犀角地黄汤合方尤其是高剂量组含药血清能够在体外调节ITP患者CD4+T细胞的过度增殖分化及细胞因子的分泌,这可能是犀角地黄汤合方治疗ITP机制之一.

OBJECTIVE To observe the effects of drug-containing serum of Xijiao Dihuang combined prescription(XJDH) on the related functions of dendritic cells(DCs) induced in vitro, and to explore the mechanisms underlying the effectiveness of XJDH treatment on primary immune thrombocytopenia(ITP). METHODS Peripheral blood samples were colle-ted from 6 healthy volunteers. Mononuclear cells were isolated by density gradient centrifugation, and CD14+ mononuclear cells were collected by the magnetic separation technique. CD14+ mononuclear cells were induced into immature DCs by recombinant human granulocyte-macrophage colony stimulating factor (GM-CSF) and recombinant human interleukin 4 (IL-4). Immature DCs were divided into three groups: control group, model group and XJDH group. CCK-8 assay was used to determine the intervention concentration and time of drug-containing serum. Lipopolysaccharide(LPS) with the final concentration of 1 μg/ml was added to model group and XJDH group respectively for 24 h to induce DCs maturation. Normal rat serum was added to control group and model group, and XJDH was added to XJDH group for 24 h. Flow cytometry was used to detect the levels of CD80, CD83 and HLA-DR on the surface of DCs. Western blot was used to detect the expression of TLR4 and NF-κB, and levels of IL-6, IL-12 and TNF-α in cell supernatant was detected by ELISA. RESULTS Compared with the control group, LPS stimulation increased the expression of CD80, CD83 and HLA-DR, with subsequent increasing expression of TLR4 and NF-κB, as well as IL-6, IL-12 and TNF-α increased(P<0.05). In comparison with model group, the expression of DCs surface molecules CD80, CD83 and HLA-DR, DCs' expression of TLR4 and NF-κB protein, and the levels of IL-6, IL-12 and TNF-α in the cell supernatant of XJDH group decreased after the intervention of XJDH (P<0.05). CONCLUSION Drug containing serum of Xijiao Dihuang combined prescription can down-regulate TLR4/NF-κB signaling pathway related protein expression, inhibit DCs maturation, and reduce proinflammatory factor secretion, which may be one of the mechanisms of drug-containing serum of Xijiao Dihuang combined prescription in the treatment of immune thrombocytopenia.

免疫介导的非恶性血液病(NMHDs)需要联合强效免疫抑制剂治疗,这些药物会降低宿主的防御功能,常常伴随感染的发生.NMHDs患者自身有细胞免疫或体液免疫的缺陷,并常需要联合强效免疫抑制剂治疗,导致治疗相关的机会感染风险增加.感染的出现很大程度上影响患者的预后.因此,及时的传染病筛查、适当的抗菌预防治疗和免疫接种等预防策略,对于降低感染风险以及改善患者预后非常重要.

Rituximab has been widely used in many autoimmune diseases.

The aim of this study is to compare the curative effect of empirical with diagnostic-driven (pre-emptive) therapy of voriconazole in severe aplastic anaemia patients (SAAs) with invasive fungal disease (IFD) after intensive immunosuppressive therapy (IST). Patients undergoing voriconazole antifungal therapy were randomized to empirical therapy group and diagnostic-driven therapy group. Empirical therapy group accounted for 48.5% of all cases, and diagnostic-driven therapy group accounted for 51.5%. The morbidity of IFD (probable and proven cases) was slightly increased in diagnostic-driven therapy group compared with empirical therapy group (P > 0.05). The total effective rate was 62.1%. The effective rate in empirical therapy group was 78.1%, which was significantly increased compared with diagnostic-driven therapy group (47.1%) (P < 0.05). This value was especially significant in possible IFD cases (P < 0.05). The efficacy of possible IFD cases in empirical therapy group was the best (84%) followed by the probable and proven cases in empirical therapy group (57.1%). In diagnostic-driven therapy group, the efficacy of possible IFD cases was 50%, and the efficacy of probable and proven cases was only 37.5%. The difference was statistically significant (P < 0.05). Absolute neutrophil count (ANC) is the key anti-infection factor. The efficacy of patients whose ANC ˂ 0.1 × 109/L was 39.28%, which was significantly reduced compared with that of patients whose ANC ≥ 0.1 × 109/L (78.95%) (P < 0.05). This finding was especially obvious in diagnostic-driven therapy group. As empirical therapy is superior to diagnostic-driven therapy, we recommend that empirical therapy should be started for high-risk patients, and efforts should be made to definitively diagnose the disease.

T cell differentiation is a key pathological process of aplastic anemia (AA). Tregs and Th17 must be balanced for efficient immune tolerance. Discorea nipponica saponins (DNS) improves the recovery from hematopoiesis in AA models through its ability to increase the number of T-helper cells whilst decreasing the percentage of T-cytotoxic cells in AA mice. However, the mechanisms by which DNS leads to these therapeutic effects remains largely undefined. Here, we explored the mechanism(s) by which DNS regulates T cell subsets in mouse AA models. BALB/c male mice were used to establish the AA model using Cs-137 irradiation and intraperitoneal injection with cyclophosphamides and Chloramphenicol. Mice were administrated DNS/Tripterygium wilfordii polyglycoside tablets (TW)/cyclosporine A (CsA)/distilled water via gavage each day for 14 days. Peripheral blood, spleen and bone marrow were obtained. Bone marrow morphology, Notch/RBPJ kappa/FOXP3/ROR gamma t signaling and molecules regulating Th17/Treg balance were evaluated. We found that DNS-M attenuated pancytopenia in mouse AA models. DNS-M could not only suppressed Th17 cell numbers and ROR gamma t expression, but enhanced the prevalence of Treg cells and Foxp3 expression. Moreover, DNS-M modulated the level of Notch1, Jagged1, RBPJ kappa, FOXP3, ROR gamma t, DLL4 in AA models. These data suggest that the administration of DNS-M exhibits therapeutic effects through restoring the Th17/Treg cell balance in AA mice through its regulation of the Notch/RBPJ kappa/FOXP3/ROR gamma t pathway. (C) 2020 The Author(s). Published by Elsevier B.V. on behalf of King Saud University.

OBJECTIVE To study the correlation of IL-37 with T lymphocytes subsets and NK cells in ITP patients, and to explore its possible mechanisms involved in the pathogenesis of ITP. METHODS Forty-five patients with newly diagnosed ITP(newly diagnosed group), 32 patients of complete remission (remission group) and 22 healthy persons(control group) were selected. The serum level of IL-37 in 3 groups was determined by enzyme linked immunosorbent assay (ELISA). The mRNA expression of IL-37, IL-17 and IL-18 in peripheral blood mononuclear cells（PBMNC） in 3 groups was measured by real-time fluorescence quantitative polymerase chain reaction (PCR). The number of IL-18Rα+CD4+ T cells and Tim-3+NK cells in the peripheral blood in 3 groups was detected by flow cytometry (FCM). RESULTS The serum level of IL-37 in the peripheral blood of ITP patients in the newly diagnosed group was significantly higher than that in the control group and the remission group(P＜0.01) . The expression level of IL-37 in PBMNC of the ITP patients in newly diagnosed group was higher than that in the control group and the remission group(P＜0. 05). The expression level of IL-17 and IL-18 in PBMNC of the ITP patients in newly diagnosed group was higher than that in the control group and the remission group(P＜0. 01); the expression of IL-18Rα in CD4+ T cells in newly diagnosed group was significantly higher than that in both the control and the remission group(P＜0.01).The expression of Tim-3 in NK cells in ITP patients was significantly lower than that in the control group (P＜0. 01). In ITP patients, the serum IL-37 level and IL-18Rα+CD4+T cells ratio both negatively correlated with Plt count (r=-0.58, r=-0.48) moreo-ver the serum IL-37 level also negatively correlated with amount of CD4+ T cells and NK cells (r=-0.29, r=-0.28), but positively correlated with amount of CD8+ T cells (r=0.329). CONCLUSION The IL-37 and its receptors may play an immunoregulatory role in CD4+ T cells and NK cells, the IL-37 may be a therapeutic target for ITP patients.

Background: Previous research showed that virus infection is correlated with the occurrence, development, and prognosis of AA. This study was designed to explore the influence of virus infection on the immune functionality and immunosuppressive therapy (IST) efficiency of newly diagnosed SAA patients. Methods: Fifty-six newly diagnosed SAA patients combined with virus infection treated in the Hematology Department of Tianjin Medical University General Hospital from October 2004 to July 2014 were studied. Various immune parameters were tested and compared for SAA patients with and without virus infection. Results: When compared with SAA patients without corresponding virus infection, SAA patients with CMV-IgM, PVB19-IgM, and EBV infection had increased CD8(+)T cell percentage, decreased CD4(+)/CD8(+) T cell ratios, and increased CD8(+)HLA-DR+/CD8(+) percentage. The absolute value of CD8(+)T cell of CMV-IgM group had increased as well. The CMV-IgM and PVB19-IgM groups showed decreased CD4(+)T cell percentage, and decreased CD4(+) HLA-DR(+/)CD8(+) HLA-DR+ ratio. The PVB19-IgM group exhibited decreased CD4(+) HLA-DR+/CD4(+) percentage, increased Th1 percentage and increased pDC percentage. Patients with EB virus infection showed lower NK cell percentage. Three years after IST, the treatment is significantly less effective for the SAA patients combined with virus infection than those without. Conclusions: CMV, PVB19, and EBV infection worsen the immune functionality abnormality of newly diagnosed SAA patients and reduce the IST efficiency.

To investigate if variations in immune and hematopoietic parameters correlated with immunosuppressive therapy (IST) in severe aplastic anemia (SAA) patients. A total of 115 SAA patients who received IST were included. Their immune and hematopoietic functionality changes had been evaluated at 0, 0.5, 1, 2, and 3-year(s) IST. For SAA patients with complete remission (CR), the CD4(+)/CD8(+)T cell ratio continued to increase after a year of IST. The T helper (Th) 1/Th2 ratio continued to decrease after 6 months of IST, as did the activated CD8(+)T cell percentage. The myeloid dendritic cell (mDC)/plasmacytoid dendritic cell (pDC) ratio after 3 years of IST was significantly lower compared to that of untreated patients. The mDC/pDC and Th1/Th2 ratios exhibited positive correlation. The activated CD8(+)T cell percentage and the number of peripheral blood neutrophils showed inverse correlation. For SAA patients with partial remission (PR), the CD4(+)T cell percentage increased at 1-year post-IST, but the later changes were not statistically significant. The other immune indexes of patients in partial remission group and nonremission (NR) group showed no obvious recovery. For all SAA patients, the percentage of T regulatory cells in CD4(+) lymphocyte was higher in post-IST group compared to the pretreatment group. For SAA patients responded well to IST, increase in peripheral neutrophils and improvement in bone marrow myeloid cells were first observed followed reduction in the activated CD8(+)T cell percentage, Th1/Th2 ratio, CD4(+)/CD8(+) T ratio, along with mDC/pDC ratio, all of which negatively correlated with the hematopoietic parameters. This demonstrates that IST prompts improvements of hematopoietic functionalities of the SAA patients by regulating their immune functionalities.

Autoimmune haemolytic anaemia (AIHA) is a kind of autoimmune diseases characterized by autoantibodies which produced and secreted by abnormal activated B lymphocytes directed against red blood cells (RBC). Study reveals that about 50% AIHA mainly occurs secondary to lymphoproliferative disorders (LPD) and autoimmune diseases. In this study, we aim to explore the characteristics of patients with AIHA secondary to LPD. Fifteen patients with AIHA secondary to LPD (secondary group) and 60 with primary AIHA (primary group) were retrospectively included. Patients in the secondary group [(59.40 ± 4.74) y] were older than those in the primary group [(47.53 ± 2.30) y] (p = 0.024). Reticulocyte counts were lower for the secondary group [(134.55 ± 20.67) × 109/L] than for the primary group [(193.88 ± 27.32) × 109/L] (p = 0.09). Haptoglobin was higher in the secondary (0.75 ± 0.19) g/L than in the primary group (0.34 ± 0.05) g/L (p = 0.004). The ratio of CD3+CD4+/CD3+CD8+ was higher in the secondary (1.81 ± 0.41) than in the primary (1.05 ± 0.12) group (p = 0.025). Duration of remission was shorter in the secondary [(23.52 ± 5.20) months] than in the primary [(40.87 ± 3.92) months] group (p = 0.013). Relapse rate was higher for the secondary (33.3%) than for the primary (8.3%) group (p = 0.003). Mortality rate was higher in the secondary (33.3%) than in the primary (8.3%) group (p = 0.003). Progression-free survival was shorter in the secondary than in the primary group (p = 0.021). In conclusion, patients with AIHA secondary to LPD showed higher age at diagnosis, shorter remission time, and higher recurrence and mortality rates than did those with primary AIHA.

OBJECTIVE:To analyze the number of myeloid-derived suppressor cells(MDSC) and the level of prostaglandin E2(PGE2) in the bone marrow of adult ITP patients, and to explore their possible mechanisms involved in the pathogenesis of this disease.METHODS:Twenty-five patients of newly diagnosed ITP, 25 patients of complete remission group and 15 patients of control group were selected. The number of MDSC in the bone marrow between 3 groups was detect by flow cytometry (FCM). The serum level of prostaglandin E2 (PGE2) in 3 groups was determined by enzyme linked immunosorbent assay (ELISA). The relative expression of IFN-γ mRNA in bone marrow mononuclear cells was measured by real time fluorescence quantitative polymerase chain reaction (RT-qPCR) in each groups.RESULTS:The number of MDSC in the complete remission group was significantly higher than that in the control group (P<0.05); the number of MDSC in the newly diagnosed group was higher than that in the control group; the number of MDSC in the complete remission group was higher than that in the newly diagnosed group. The serum level of PGE2 in bone marrow of ITP patients in the newly diagnosed group was higher than that of the control group（P<0.05）. The serum level of PGE2 in the bone marrow of ITP patients of the complete remission group was higher than that of the control group (P<0.05）. The level of PGE2 in bone marrow serum of ITP patients of the newly diagnosed group was lower than that in the complete remission group(P<0.05）. The relative expression level of IFN-gamma in bone marrow mononuclear cells of the ITP patients in newly diagnosed group was higher than that in the control group and the complete remission group（P<0.001）. The relative quantification (RQ) of IFN-γ in bone marrow mononuclear cells was 2.60 between the newly diagnosed group and the complete remission group.CONCLUSION:When adult ITP disease is remitted, the number of MDSC rises and correlates with the therapeutic response and PGE2 level in the bone marrow.

再生障碍性贫血是一种外周全血细胞减少的骨髓衰竭综合征.感染是再生障碍性贫血患者死亡的主要原因.再生障碍性贫血患者的免疫妥协状态与化疗导致的中性粒细胞减少的免疫妥协状态不同,其导致的感染也有所不同.长期粒细胞减少是发生侵袭性真菌病和细菌感染的最大危险因素.中性粒细胞减少的恢复能明显提高生存率,粒细胞减少期间的支持治疗可起到很大的保护作用.再生障碍性贫血患者合并侵袭性真菌病最常见的致病菌为曲霉菌属、假丝酵母菌属、接合菌属和镰刀菌属.合并细菌感染的致病菌包括:革兰阳性菌如凝固酶阴性的葡萄球菌属、肠球菌、凝固酶阳性的金黄色葡萄球菌、梭状芽胞杆菌、微球菌甲型溶血性链球菌、单核细胞增生李斯特菌、蜡样芽胞杆菌;革兰阴性菌如大肠埃希杆菌、沙门菌、脆弱拟杆菌、肺炎克雷伯杆菌、亲水性气单胞菌属、铜绿假单胞菌.再生障碍性贫血患者合并病毒感染相对少见,但可出现疱疹病毒科、社区获得性呼吸道病毒感染和甲型、乙型、丙型病毒性肝炎.

Objective: To summarize the clinical characteristics of acquired pure red cell aplasia (PRCA) patients diagnosed in our hospital in the last 10 years. Method: The clinical features, immune state and treatment response of acquired PRCA patients diagnosed in our hospital from January 2007 to January 2017 were retrospectively analyzed. Results: The results showed that thymoma (13.21%) and parvovirus B19 (11.32%) were the most common causes for secondary PRCA. Ferritin (Fer) levels and erythropoietin (EPO) levels were increased in PRCA patients. The total CR and PR rate of immunosuppressive therapy in our studies was 68.29% and 12.20%, respectively. Patients with EPO level >400 U/L and Fer level >200 ng/ml had significantly lower CR rate than others. The patients with EPO level >400 U/L also had longer hemoglobin recovery time than patients with EPO level <= 400 U/L. Patients treated with corticosteroids (CS) + cyclosporine A (CsA) had lower relapse rate compared to the CS group (29.17% vs. 80.00%, P < .05). Conclusion: Our data showed that patients with PRCA had high EPO and Fer levels. Thymoma and viral infections are the most common causes for secondary PRCA. The CS+ CsA group had lower relapse rate than CS group although response rate was similar. Increased EPO and Fer levels might be the negative factors for prognosis of acquired PRCA.

目的 探讨中性粒细胞缺乏血液病患者发生嗜麦芽窄食单胞菌败血症的临床特征和预后因素.方法 回顾性分析我科2006年1月—2016年12月收治的32例发生嗜麦芽窄食单胞菌败血症合并中性粒细胞缺乏患者的临床资料.结果 32例患者中急性白血病20例,重型再生障碍性贫血(SAA)7例,非霍奇金淋巴瘤5例.所有患者长时间应用广谱抗生素,中心静脉置管(21例)或者外周静脉置管(11例).25例化疗后出现中性粒细胞缺乏,7例SAA为本病导致中性粒细胞缺乏.死亡17例,好转15例.药敏试验显示多药耐药,替加环素、甲氧苄啶-磺胺甲噁唑、左氧氟沙星、头孢哌酮/舒巴坦、头孢他啶、哌拉西林/他唑巴坦部分敏感,其余均耐药.重度中性粒细胞缺乏、重度血小板减少、粒细胞减少持续时间过长和复合感染等是预后不良因素.结论 中性粒细胞缺乏血液病患者并发嗜麦芽窄食单胞菌败血症死亡率高,及时诊断和治疗对预后至关重要.

We aimed to investigate the efficacy and safety of de-escalation empirical therapy for controlling infection in patients with severe aplastic anaemia (SAA) treated with antithymocyte globulin (ATG). Eighty-seven ATG-treated SAA patients who had microbiological culture-confirmed infections from 2006 to 2015 in our center were retrospectively analyzed. The efficacy of de-escalation and non-de-escalation therapy was compared. Among all 87 patients, 63 patients were treated with de-escalation therapy and 24 patients with non-de-escalation therapy. More patients showed response to anti-infection treatment in de-escalation group than in non-de-escalation group both on day 7 (60.32% vs. 25.00%, P = 0.003) and on day 30 (79.37% vs. 58.33%, P = 0.047) since the initial antimicrobial therapy. On day 30, more patients had increased absolute neutrophil count in de-escalation group compared with non-de-escalation group (76.19% vs. 45.83%, P = 0.007), and de-escalation group had lower morality rate (17.46% vs. 37.50%, P = 0.047) and better survival outcome (P = 0.023) on day 90. Twenty-three patients in de-escalation group and 5 patients in non-escalation group received granulocyte transfusions. Granulocyte transfusions helped to control infections in both de-escalation group (P = 0.027) and non-de-escalation group (P = 0.042) on day 7, but did not improve survival on day 90. We concluded that de-escalation antibiotics improved survival in SAA patients after ATG treatment. Early administration of broad-spectrum antibiotics pending microbiological cultures combined with a commitment to change to narrow-spectrum antibiotics should be recommended for controlling infections in SAA patients treated with ATG. Granulocyte transfusions might be an adjunctive therapy in controlling infections.