Bone marrow transplantation

骨髓移植
  • 文章类型: Journal Article
    许多恶性血液病患者在化疗/调理后但在化疗诱导的中性粒细胞减少症(中性粒细胞减少性发热[PNF])之前出现发热。具有感染性病因的PNF的比例尚未确定。
    我们进行了单中心,PNF的前瞻性观察性亚研究(中性粒细胞>0.5个细胞/μL,≥38.0°C)在接受急性髓性白血病(AML)化疗的成人中,或异基因造血细胞移植(allo-HCT)预处理纳入2018年1月1日至10月31日的中性粒细胞减少性发热随机对照试验.符合条件的患者预期中性粒细胞减少症≥10天,排除包括化疗或预处理前并发感染和/或中性粒细胞减少症。描述了PNF比率和遇到的感染。探讨了非感染性病因与发热之间的关联。检查了中性粒细胞减少前期和中性粒细胞减少期的抗菌治疗处方。
    包括62例连续患者(43例allo-HCT,19AML),27人患有PNF(44%),5人(19%)有感染原因。在allo-HCT中,接受胸腺球蛋白的17人中有14人(82%)发生PNF;14人中只有1人(7%)感染。在AML化疗期间,19人中有18人接受了阿糖胞苷,其中18人中有8人(44%)感染了PNF,8人中有3人(38%)感染。大多数PNF患者的抗菌治疗持续到中性粒细胞减少期(19/27[70%])。患有PNF的患者在中性粒细胞减少性发热时/期间更有可能升级为更广泛的抗菌治疗(5/24[21%]vs2/30[7%])。
    PNF的比率很高,记录在案的感染率低,导致长期和逐步升级的抗菌治疗。在没有感染的情况下,建议在PNF后早期停止经验性治疗作为一项重要的管理干预措施.
    UNASSIGNED: Many patients with hematological malignancy develop fever after chemotherapy/conditioning but before chemotherapy-induced neutropenia (preneutropenic fever [PNF]). The proportion of PNF with an infectious etiology is not well established.
    UNASSIGNED: We conducted a single-center, prospective observational substudy of PNF (neutrophils >0.5 cells/μL, ≥38.0°C) in adults receiving acute myeloid leukemia (AML) chemotherapy, or allogeneic hematopoietic cell transplant (allo-HCT) conditioning enrolled in a neutropenic fever randomized controlled trial between 1 January and 31 October 2018. Eligible patients had anticipated neutropenia ≥10 days and exclusions included concurrent infection and/or neutropenia prior to chemotherapy or conditioning. PNF rates and infections encountered were described. Associations between noninfectious etiologies and fever were explored. Antimicrobial therapy prescription across preneutropenic and neutropenic periods was examined.
    UNASSIGNED: Of 62 consecutive patients included (43 allo-HCT, 19 AML), 27 had PNF (44%) and 5 (19%) had an infective cause. Among allo-HCT, PNF occurred in 14 of 17 (82%) who received thymoglobulin; only 1 of 14 (7%) had infection. During AML chemotherapy, 18 of 19 received cytarabine, of which 8 of 18 (44%) had PNF and 3 of 8 (38%) had infection. Most patients with PNF had antimicrobial therapy continued into the neutropenic period (19/27 [70%]). Those with PNF were more likely to be escalated to broader antimicrobial therapy at onset/during neutropenic fever (5/24 [21%] vs 2/30 [7%]).
    UNASSIGNED: Rates of PNF were high, and documented infection low, leading to prolonged and escalating antimicrobial therapy. In the absence of infection, early cessation of empiric therapy after PNF is recommended as an important stewardship intervention.
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  • 文章类型: Journal Article
    背景:评估多学科的康复策略对于先发制人地对抗身体,急性髓系白血病(AML)和骨髓增生异常综合征(MDS)患者的异基因造血干细胞移植(allo-HSCT)过程中经历的心理和社会负面影响。目前的证据仅限于诱导化疗期间的研究,省略康复干预措施,主要使用仅运动的方法,而没有多学科框架。这项研究的目的是探讨可行性,成人多学科康复的安全性和初步疗效提供allo-HSCT。
    方法:这项为期8周的单组可行性研究旨在为接受allo-HSCT的参与者试行多学科康复干预,注重可行性和安全性。参与者,18岁或以上,诊断为AML或MDS,并提供allo-HSCT,将在2023年6月至2024年7月期间招募。多学科康复干预,由皇家阿德莱德医院的癌症专职医疗小组进行,包括运动生理学,物理治疗,营养学,社会工作,职业治疗和心理干预。与多学科治疗方法一致,每个组件都是针对患者护理的不同方面量身定制的,和依从性计算将评估患者的参与度和依从性。此外,参与者将继续接受癌症专职医疗人员的常规护理。该研究的主要结果是通过评估干预措施的吸收来评估多学科康复干预的可行性。保留,坚持,可接受性和安全性。次要结果是腿部力量,上身强度,有氧健身,跌倒风险,人体测量学,营养状况,生活质量,焦虑,抑郁症,应对癌症和痛苦的自我效能感。
    背景:本研究的伦理批准已由阿德莱德中央地方卫生网络(HREC2022/HRE00284)提供。该研究的招聘始于2023年6月,并将持续到2024年7月。这些方法已根据SPIRIT和CONSORT试点研究清单进行了设计和报告。
    背景:澳大利亚新西兰临床试验注册中心(ANZCTR):ACTRN12623000052639。
    BACKGROUND: Assessing multidisciplinary prehabilitation strategies becomes crucial to pre-emptively counter the physical, psychological and social negative impacts experienced during an allogenic haematopoietic stem cell transplant (allo-HSCT) among acute myeloid leukaemia (AML) and myelodysplastic syndrome (MDS) patients. Current evidence is restricted to studies during induction chemotherapy, omitting rehabilitation interventions and predominantly using exercise-only approaches without a multidisciplinary framework. The aim of this study is to investigate the feasibility, safety and preliminary efficacy of multidisciplinary prehabilitation in adults offered allo-HSCT.
    METHODS: This 8-week single-group pre-post feasibility study aims to pilot a multidisciplinary prehabilitation intervention for participants undergoing allo-HSCT, with a focus on feasibility and safety. Participants, aged 18 or older, diagnosed with AML or MDS, and offered allo-HSCT, will be recruited between June 2023 and July 2024. The multidisciplinary prehabilitation intervention, conducted by the cancer allied health team at the Royal Adelaide Hospital, includes exercise physiology, physiotherapy, dietetics, social work, occupational therapy and psychology interventions. Consistent with a multidisciplinary treatment approach, each component is tailored to address different aspects of patient care, and adherence calculations will assess patient engagement and compliance. In addition, participants will continue to receive usual care from cancer allied health staff. The primary outcome of the study is to assess the feasibility of a multidisciplinary prehabilitation intervention by evaluating intervention uptake, retention, adherence, acceptability and safety. Secondary outcomes are leg strength, upper-body strength, aerobic fitness, falls risk, anthropometry, nutritional status, quality of life, anxiety, depression, self-efficacy for coping with cancer and distress.
    BACKGROUND: Ethics approval for this study has been provided by the Central Adelaide Local Health Network (HREC 2022/HRE00284). Recruitment for the study commenced in June 2023 and will continue until July 2024. The methods have been designed and are reported according to the SPIRIT and CONSORT-pilot study checklist.
    BACKGROUND: The Australian New Zealand Clinical Trials Registry (ANZCTR): ACTRN12623000052639.
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  • 文章类型: Journal Article
    HLA-A*23:140等位基因与HLA-A*23:01:01的差异在于一个核苷酸取代(G>A),1968年外显子5的位置。
    The HLA-A*23:140 allele differs from HLA-A*23:01:01 by one nucleotide substitution (G > A), position 1968 in exon 5.
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  • 文章类型: Journal Article
    新型HLA-B*18:37:03等位基因,首先在来自巴西的潜在骨髓捐献者中描述。
    The novel HLA-B*18:37:03 allele, first described in a potential bone marrow donor from Brazil.
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  • 文章类型: Case Reports
    背景:奈梅亨断裂综合征(NBS)是一种常染色体隐性遗传DNA修复障碍,表现为基因组不稳定性增加,恶性肿瘤,细胞和体液免疫缺陷。由于NBS患者对致命感染和淋巴增生性恶性肿瘤的易感性增加,因此预后较差。目前,NBS没有特定的治疗方法,尽管已经进行了异基因造血干细胞移植(HSCT),并将其记录为病例系列,以证明移植的实用性。
    方法:一名14岁女孩因反复肺部感染而患有NBS和哥哥的单倍体HSCT,因肝硬化而接受肝移植(LT)。肝肺综合征(HPS),怀疑肝脏恶性肿瘤.决定使用先前为HSCT捐赠的活体捐赠者进行LT。
    结果:活体供体左叶LT从她的兄弟处成功完成。患者术后早期无并发症,术后第七天出院。肝脏的病理学检查显示两个病灶中的“中间细胞癌”。经过1年的LT,患者在LT并发症和感染方面进展顺利,最小的免疫抑制。
    结论:NBS患者的恶性肿瘤患病率增加,包括原发性肝脏恶性肿瘤,但大多数都是通过医疗或有限的切除来管理的。这些患者的移植可以治愈肝脏恶性肿瘤,具有良好的安全性。
    BACKGROUND: Nijmegen breakage syndrome (NBS) is an autosomal recessive DNA repair disorder that manifests through increased genomic instability, malignancy, and cellular and humoral immunodeficiencies. The prognosis for NBS patients is poor due to their increased susceptibility to fatal infections and lymphoproliferative malignancies. Currently, there is no specific treatment for NBS, though allogeneic hematopoietic stem cell transplantation (HSCT) has been performed and documented as case series to demonstrate the utility of transplantation.
    METHODS: A 14-year-old girl with NBS and haploidentical HSCT from her older brother due to recurrent lung infection was referred for liver transplantation (LT) due to liver cirrhosis, hepatopulmonary syndrome (HPS), and suspicion of liver malignancy. It was decided to perform LT using the living donor who had previously donated for HSCT.
    RESULTS: Living donor left lobe LT was successfully performed from her brother. The patient experienced no complications in the early postoperative period and was discharged on the seventh postoperative day. Pathological examination of extracted liver has shown \"intermediate cell carcinoma\" in two foci. After 1 year LT, the patient has had an uneventful course in terms of LT complications and infection, with minimal immunosuppression.
    CONCLUSIONS: NBS patients have an increased prevalence of malignancies, including primary hepatic malignancy, but most are managed medically or with limited resections. Transplantation in these patients can be curative for hepatic malignancy with a favorable safety profile.
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    文章类型: English Abstract
    BACKGROUND: the pandemic of COVID-19 has led to clinical complications such as avascular necrosis of the femoral head (AVNFH) associated with the use of corticosteroids. The aim of the study is to report the functional and radiographic results of 13 patients with post-COVID-19 ANFH after decompression using Forage and bone marrow aspirate concentrate (BMAC).
    METHODS: single-center, prospective, uncontrolled clinical study. From April 2020 to September 2021, 13 patients (21 hips) with post-COVID-19 ANFH were treated. All received corticosteroids during infection (average daily dose: 480 mg). Clinical, radiographic and magnetic resonance imaging evaluations were performed; the Ficat classification was applied for the classification of AVNFH. The surgical technique used was decompression with Forage and ACMO.
    RESULTS: the mean age was 47 years, with a follow-up of 30.4 months. Symptoms appeared with a mean of 4.2 months after COVID-19 infection. Harris score improved from 41.2 ± 5.2 to 86.6 ± 3.4. Radiographic evaluation showed that 14.3% of the sample experienced femoral head collapse and underwent total hip arthroplasty.
    CONCLUSIONS: post-COVID-19 ANFH is a clinical entity with rapid progression and different degrees of severity. Decompression with Forage and ACMO seems a promising initial treatment, however, the variable response and the probability of collapse emphasize the importance of long-term follow-up and identification of patients who may require additional interventions.
    UNASSIGNED: la pandemia de COVID-19 ha dado lugar a complicaciones clínicas como la necrosis avascular de la cabeza femoral (NAVCF) asociada con el uso de corticoesteroides. El objetivo del estudio es reportar los resultados funcionales y radiográficos de 13 pacientes con NAVCF post-COVID-19, después de la descompresión utilizando Forage y aspirado de células de medula ósea (ACMO).
    UNASSIGNED: estudio clínico unicéntrico, prospectivo, no controlado. Desde Abril de 2020 hasta Septiembre de 2021, se trataron 13 pacientes (21 caderas) con NAVCF post-COVID-19. Todos recibieron corticoesteroides durante la infección (dosis promedio diaria: 480 mg). Se realizaron evaluaciones clínicas, radiográficas y por resonancia magnética nuclear; se aplicó la clasificación de Ficat para la clasificación de NAVCF. La técnica quirúrgica empleada fue descompresión con Forage y ACMO.
    RESULTS: la edad promedio fue 47 años, con un seguimiento de 30.4 meses. Los síntomas aparecieron con una media de 4.2 meses después de la infección por COVID-19. La escala de Harris mejoró de 41.2 ± 5.2 a 86.6 ± 3.4. La evaluación radiográfica demostró que 14.3% de la muestra experimentó colapso de la cabeza femoral por lo que se les realizó artroplastía total de cadera.
    CONCLUSIONS: la NAVCF post-COVID-19 es una entidad clínica con rápida progresión y diferentes grados de severidad. La descompresión con Forage y ACMO parece un tratamiento inicial prometedor; sin embargo, la respuesta variable y la probabilidad de colapso, enfatizan la importancia de seguimiento a largo plazo e identificación de los pacientes que puedan requerir intervenciones adicionales.
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  • 文章类型: Journal Article
    基于荧光素-荧光素酶反应的发光技术作为定量成像模态已广泛用于各种学科。由于其非侵入性成像能力,它已经发展成为一种有价值的体内生物成像工具,特别是在基因和细胞疗法等领域的小动物模型中。我们先前已经成功地产生了在Rosa26基因座上系统表达荧光素酶基因的大鼠。在这项研究中,我们将这些大鼠的骨髓移植到微型猪体内,并使用体内成像技术对移植细胞的动力学进行非侵入性分析。此外,我们确定大鼠到猪的移植系统是一个不和谐的系统,类似于猪到人的移植系统。因此,大鼠-猪移植可以为猪-人异种移植提供临床上合适的大型动物模型.
    Luminescent technology based on the luciferin-luciferase reaction has been extensively employed across various disciplines as a quantitative imaging modality. Owing to its non-invasive imaging capacity, it has evolved as a valuable in vivo bioimaging tool, particularly in small animal models in fields such as gene and cell therapies. We have previously successfully generated rats with a systemic expression of the luciferase gene at the Rosa26 locus. In this study, we transplanted bone marrow from these rats into micro-mini pigs and used in vivo imaging to non-invasively analyze the dynamics of the transplanted cells. In addition, we established that the rat-to-pig transplantation system is a discordant system, similar to the pig-to-human transplantation system. Thus, rat-to-pig transplantation may provide a clinically appropriate large animal model for pig-to-human xenotransplantation.
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  • 文章类型: Journal Article
    通过对患有GVHD的小鼠的角膜进行蛋白质组学分析来鉴定对眼部移植物抗宿主病(GVHD)具有特异性的分子特征。
    我们在骨髓移植4周后鉴定了来自GVHD模型小鼠和同基因对照小鼠的角膜样品中的差异表达蛋白(DEP)。对单个样品进行数据独立采集分析,通过生物信息学和京都基因和基因组百科全书(KEGG)分析,评估了DEP在与GVHD相关的生物学途径中的作用。
    GVHD小鼠角膜中三个重要的信号通路上调:(1)坏死通路,(2)丝裂原活化蛋白激酶(MAPK)通路,和(3)如先前报告的那样,中性粒细胞胞外诱捕网(NET)通路。在这些信号通路中,我们发现了新的上调分子,包括(1)受体相互作用蛋白激酶1(RIPK1),RIPK3,干扰素调节因子9,干扰素诱导的双链RNA活化蛋白激酶脂氧合酶,和高迁移率族box1(HMGB1)是坏死途径中的损伤相关分子模式(DAMPs);(2)顺序上调的白介素1(IL-1)受体相关激酶(IRAK),Toll途径(ECSIT)中进化保守的信号中间体,和p38,它是IL-1受体的下游和增加的CDC42/Rac(Rac2),MAPK通路中的Rho家族GTPase;和(3)整合素成分CR3和巨噬细胞-1抗原(MAC-1),它们是DAMPs,NET通路中的焦亡相关蛋白gasderminD(GSDMD)。
    这些新分子可能有助于研究人员阐明GVHD的发病机制,并确定眼部GVHD患者角膜改变的新治疗靶点。
    UNASSIGNED: To identify molecular signatures specific for ocular graft-versus-host disease (GVHD) by proteomic analysis of corneas from mice with GVHD.
    UNASSIGNED: We identified differentially expressed proteins (DEPs) in corneal samples from GVHD model mice and syngeneic control mice 4 weeks after bone marrow transplantation. Data-independent acquisition analysis was performed on individual samples, and the roles of DEPs in biological pathways related to GVHD were evaluated via bioinformatics and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses.
    UNASSIGNED: Three important signaling pathways were upregulated in the cornea in mice with GVHD: (1) the necroptosis pathway, (2) the mitogen-activated protein kinase (MAPK) pathway, and (3) as previously reported, the neutrophil extracellular trap (NET) pathway. In those signaling pathways, we identified new upregulated molecules, including (1) receptor-interacting protein kinase 1 (RIPK1), RIPK3, interferon regulatory factor 9, the interferon-induced double-stranded RNA-activated protein kinase lipoxygenase, and high mobility group box1 (HMGB1) which are damage-associated molecular patterns (DAMPs) in the necroptosis pathway; (2) the sequentially upregulated interleukin 1 (IL-1) receptor-associated kinase (IRAK), an evolutionarily conserved signaling intermediate in the Toll pathway (ECSIT), and p38, which is downstream of the IL-1 receptor and increased CDC42/Rac (Rac2), a Rho family GTPase in the MAPK pathway; and (3) the integrin components CR3 and macrophage-1 antigen (MAC-1), which are DAMPs, and the pyroptosis-related protein gasdermin D (GSDMD) in the NET pathway.
    UNASSIGNED: These novel molecules may help researchers elucidate the pathogenesis of GVHD and identify new therapeutic targets for corneal changes in patients with ocular GVHD.
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  • 文章类型: Journal Article
    骨髓干细胞(BM-SC)及其后代在组织修复和再生中起着核心作用。慢性肝衰竭患者,骨髓(BM)储备受到严重损害,并且在损伤和感染的解决方面表现出明显的缺陷,导致肝功能衰竭和失代偿的发作。尚不清楚BM衰竭是否是肝硬化期间肝衰竭的原因或后果。在这项研究中,我们的目的是确定BM失败和肝硬化再生失败之间的潜在关系。
    C57Bl/6(J)小鼠通过腹膜内施用四氯化碳(CCl4)15周(0.1-0.5ml/kg)发展慢性肝损伤。处死动物以研究肝硬化和BM缺陷的转变。为了恢复BM-SC储备;通过BM内输注输注健康的BM细胞,并评估肝损伤的变化。再生,和BM-SC储备。
    使用CCl4诱导的肝硬化动物模型,我们发现BM-SCs储备的丧失发生在再生失败和非急性失代偿开始之前.健康BM细胞的BM内输注诱导肝硬化BM中天然造血干细胞(HSC)的再增殖。恢复BM-HSC储备增加肝巨噬细胞介导的感染清除和炎症抑制中性粒细胞介导的炎症,加速纤维化消退,增强肝细胞增殖,并延迟非急性代偿失调的发作。
    这些发现表明,BM-HSC储备的丧失是肝脏先天免疫功能受损的基础,驱动器再生失败,和非急性代偿失调的发作。我们进一步提供了概念验证,即恢复BM-HSC储备可以作为预防再生失败和过渡到失代偿肝硬化的潜在治疗方法。
    UNASSIGNED: Bone marrow stem cells (BM-SCs) and their progeny play a central role in tissue repair and regeneration. In patients with chronic liver failure, bone marrow (BM) reserve is severally compromised and they showed marked defects in the resolution of injury and infection, leading to liver failure and the onset of decompensation. Whether BM failure is the cause or consequence of liver failure during cirrhosis is not known. In this study, we aimed to determine the underlying relationship between BM failure and regeneration failure in cirrhosis.
    UNASSIGNED: C57Bl/6(J) mice were used to develop chronic liver injury through intra-peritoneal administration of carbon tetrachloride (CCl4) for 15 weeks (0.1-0.5 ml/kg). Animals were sacrificed to study the transition of cirrhosis and BM defects. To restore the BM-SC reserve; healthy BM cells were infused via intra-BM infusion and assessed for changes in liver injury, regeneration, and BM-SC reserve.
    UNASSIGNED: Using a CCl4-induced animal - model of cirrhosis, we showed the loss of BM-SCs reserve occurred before regeneration failure and the onset of non-acute decompensation. Intra-BM infusion of healthy BM cells induced the repopulation of native hematopoietic stem cells (HSCs) in cirrhotic BM. Restoring BM-HSCs reserve augments liver macrophage-mediated clearance of infection and inflammation dampens neutrophil-mediated inflammation, accelerates fibrosis regression, enhances hepatocyte proliferation, and delays the onset of non-acute decompensation.
    UNASSIGNED: These findings suggest that loss of BM-HSCs reserve underlies the compromised innate immune function of the liver, drives regeneration failure, and the onset of non-acute decompensation. We further provide the proof-of-concept that rejuvenating BM-HSC reserve can serve as a potential therapeutic approach for preventing regeneration failure and transition to decompensated cirrhosis.
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  • 文章类型: Journal Article
    目的:测量血液和骨髓移植病房护士和工作人员的基线工作感激;评估积极的工作场所认可干预对工作感激的影响,归属感和社区感,和工作满意度;并探讨这些变量与工作满意度之间的关系。
    总共,在一家大型学术医院的血液和骨髓移植病房,从护士和工作人员那里收集了40份调查答复(干预前=24,干预后=16)。
    干预前后的调查包括人口统计问卷和工作感恩量表。安装了面向公众的数字标牌,并用于投射积极的认可,包括患者和工作人员的感激之情。
    结果:工作满意度较高,归属感和社区感较强的人报告工作感恩分数较高。工作满意度没有显著变化,归属感和社区感,和工作感恩分数。
    结论:通过感恩和积极认可创造一个积极的工作环境,可以提高护士和员工的工作满意度、归属感和社区感。
    OBJECTIVE: To measure baseline work gratitude among nurses and staff on a blood and marrow transplantation unit; to evaluate the impact of a positive workplace recognition intervention on work gratitude, sense of belonging and community, and job satisfaction; and to explore the relationships among these variables and job satisfaction.
    UNASSIGNED: In total, 40 survey responses (preintervention =24, postintervention = 16) were collected from nurses and staff on a blood and marrow transplantation unit at a large academic hospital.
    UNASSIGNED: A pre- and postintervention survey included a demographic questionnaire and the Work Gratitude Scale. Public-facing digital signage was installed and used to project positive recognition, including expressions of gratitude from patients and staff.
    RESULTS: Those with higher job satisfaction and a stronger sense of belonging and community reported higher work gratitude scores. There were no significant changes in job satisfaction, sense of belonging and community, and work gratitude scores.
    CONCLUSIONS: Creating a positive work environment through gratitude and positive recognition could increase job satisfaction and sense of belonging and community among nurses and staff.
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