The role of occupational and environmental exposures in the aetiology of acquired severe aplastic anaemia: a case control investigation

Aplastic anaemia is a rare but serious disorder with a high morbidity and mortality rate. The causes of aplastic anaemia are, for the most part, unknown. We report on the hypothesis that aplastic anaemia may be caused by occupational and/or environmental exposures to certain chemicals. The UK Aplastic Anaemia Study was an interview-based case-control study covering the whole of Great Britain. Those patients diagnosed between 1 July 1993 and 20 October 1997, aged < or =75 years and born and diagnosed in the UK were eligible for the study. Two hundred eligible cases of aplastic anaemia were compared with 387 age- and sex-matched controls. A number of occupational exposures showed increases in risk. In a multivariate model of these exposures the odds ratios (ORs) for solvents/degreasing agents, pesticides and radiation were >2 and statistically significant. Reported chemical treatment of houses within 5 years of diagnosis had a significantly raised risk for adults [OR = 2.51, 95% confidence interval (CI) 1.02-12.01], particularly for woodworm treatment (OR = 5.1, 95% CI 1.5-17.4). This study identified significant risks associated with self-reported exposure to solvents, radiation and pesticides in the workplace. Self-reported chemical treatment of houses was also associated with an increased risk of developing aplastic anaemia, in keeping with previous literature.     

Restoration of immunity and reactivation of hepatitis B virus after immunosuppressive therapy in a patient with severe aplastic anaemia

We recently treated a patient with severe aplastic anaemia (SAA) who also had chronic hepatitis B virus (HBV) infection. The HBV serological status at the time of diagnosis of SAA was HBsAg(+) and HBeAg(+). Subsequent analysis of the precore region of HBV DNA showed wild-type. He received anti-thymocyte globulin (ATG) and cyclosporin A (CsA) therapy twice. After each course of ATG infusion and during CsA therapy he developed lymphopenia for 1 and 2.5 months, respectively. His serum alanine aminotransferase (ALT) became normalized during the period of lymphopenia, but the serum HBV viral load increased. When his peripheral lymphocytes count recovered, his ALT became elevated again. Lamivudine was effective to normalize his elevated ALT and suppress viral replication. The phenomenon observed in this case supports the prevailing notion that hepatitis B flare-up in HBV carriers after chemotherapy is caused by an immune-mediated mechanism. Meanwhile, this is the first documented case of SAA who developed HBV reactivation upon recovery of lymphopenia after immunosuppressive therapy. This also highlights the necessity of pre-emptive therapy with lamivudine in SAA/HBsAg(+) patients to receive immunosuppressive therapy with ATG/CsA.     

Successful Aortic Valve Replacement Surgery in a Patient with Severe Haemophilia a with Low Titre Inhibitor

Acute leukemia, secondary myelodysplasia and paroxysmal nocturnal hemoglobinuria evolving from severe aplastic anemia (AA) following immunosuppressive therapy are well recognized. However, severe AA occurring after complete remission of acute promyelocytic leukemia (APL) has been documented only once in 2009. We report a case of 30-year-old male diagnosed with APL who achieved complete cytogenetic remission with all-trans retinoic acid based induction regimen and developed severe AA few months later during maintenance therapy.     

Low Expression of Basic Fibroblastic Growth Factor in Mesenchymal Stem Cells and Bone Marrow of Children with Aplastic Anemia

Background: Our previous experiments with gene chip suggested that basic fibroblastic growth factor (FGF2) levels were lower in mesenchymal stem cell (MSC) from aplastic anemia patients. The purpose of this study was to determine the expression of FGF2 in MSC and in bone marrow of children with aplastic anemia to better understand the role of low FGF2 expression in the pathogenesis of aplastic anemia. Procedure: MSCs from the bone marrow of aplastic anemia children and control group were cultured in vitro. Growth curves of primary and passage MSC were plotted. FGF2 gene expression in MSCs was detected using quantitative real-time polymerase chain reaction (RT-PCR). FGF2 protein expression in mononuclear cells and FGF2 protein level in extracellular fluid of bone marrow were also investigated. Result: Decreased growth of MSCs from aplastic anemia children was observed after passage 8 in serial subcultivation, and FGF2 gene expression was downregulated. Within the patients’ bone marrow, low FGF2 expression was validated both in mononuclear cells and in the extracellular fluid. Conclusion: Low FGF2 gene expression in MSCs and low FGF2 protein level in bone marrow of aplastic anemia may involve to pathogenesis of aplastic anemia.     

Trichosporon Asahii,Sepsis, and Secondary Hemophagocytic Lymphohistiocytosis in Children with Hematologic Malignancy

Trichosporon asahii (T. asahii) is an uncommon fungal pathogen rarely seen in patients with hematologic malignancies. Although appropriate therapy is started, infection with T. asahii usually leads to mortality. Here, we describe two patients developed severe T. asahii infection and secondary HLH. Despite rapid identification of T. asahii and negative blood cultures achieved by prompt initiation of treatment with voriconazole, fever and pancytopenia, persisted and both developed hepatosplenomegaly, and their clinical state worsened. Bone marrow aspiraton revealed hemophagocytosis. Elevated ferritin, triglyceride levels were seen. The first patient did not receive HLH directed therapy and died with multiple organ dysfunctions. Prompt diagnosis and treatment of secondary HLH led to rapid improvement in clinical and laboratory abnormalities in the second patient and kept her alive. We suggest that HLH may present as a secondary condition, accompanying a severe infection with T. asahii may, at least in part, contribute to high mortality rates in these cases.     

Enhanced recruitment and hematopoietic reconstitution of bone marrow‐derived mesenchymal stem cells in bone marrow failure by the SDF‐1/CXCR4

Aplastic anemia (AA) is a bone marrow failure disease. It is difficult to treat AA, and in addition, relapses are common because of its complex disease pathogenesis. Allogeneic bone marrow‐derived mesenchymal stem cells (BMSCs) infusion is an effective and safe treatment option for the AA patients. However, it found that BMSCs infusion in AA patients is less than 30% effective. Therefore, the key to improve the efficacy of BMSCs treatment in these patients is to enhance their homing efficiency to the target sites. Studies have shown that stromal cell‐derived factor‐1 (SDF‐1)/CXC chemokine receptor 4 (CXCR4) axis plays an important role in promoting BMSCs homing. In this study, human BMSCs were transduced with lentivirus stably expressing CXCR4‐BMSCs. Transduced BMSCs resemble normal BMSCs in many ways. Migration ability of CXCR4‐BMSCs toward SDF‐1 was increased because of the overexpression of CXCR4. In the mice with bone marrow failure, the migration and colonization ability of CXCR4‐BMSCs to the bone marrow was significantly improved as seen by IVIS imaging and FACS. The SDF‐1 level in the bone marrow failure mice was significantly higher than in the normal mice. Thus, from our study, it is clear that after CXCR4‐BMSCs were infused into mice with bone marrow failure, SDF‐1 interacted with CXCR4 receptor, leading cells to migrate and colonize to bone marrow. Because of the high SDF‐1 expression in mouse bone marrow and CXCR4 receptor expression in cells, BMSCs homing was increased.     

儿童非重型再生障碍性贫血中医证候分布研究

目的 探索儿童非重型再生障碍性贫血（NSAA）的中医证候分布规律,为临床辨证治疗提供参考。方法 收集2019年1月—2021年12月期间确诊的NSAA患儿,制定证素调查问卷并进行临床信息采集,采用因子分析、聚类分析的方法,探索NSAA患儿中医证候分布规律。结果 共纳入NSAA患儿368例,收集频率>15%的中医证候共54个。因子分析获得公因子16个,NSAA患儿主要病位证素分布在脾、肾、肝,主要病性证素为气虚、血虚、阴虚、阳虚、痰湿。对16个公因子进一步进行聚类分析,最终归纳为5个中医证型,分别为脾气亏虚证、气血两虚证、肾阴虚证、肾阳虚证、肾阴阳两虚证。结论 儿童NSAA病位主要在脾、肾、肝,中医主要证型为脾气亏虚证、气血两虚证、肾阴虚证、肾阳虚证和肾阴阳两虚证。