Marrow Transfusion Research Articles

Azacitidine in combination with shortened venetoclax treatment cycles in patients with acute myeloid leukemia.

The combination of venetoclax with hypomethylating agents is currently the standard of care for elderly patients with acute myeloid leukemia (AML) ineligible for intensive chemotherapy. Despite its favorable efficacy, clinical use is often associated with post-remission cytopenia, frequently necessitating treatment delays and dose modifications. This study aims to evaluate the efficacy and safety of shortened venetoclax treatment durations. A multicenter analysis was conducted involving 20 adult AML patients receiving venetoclax (7 or 14 days with 9 and 11 patients, respectively) combined with 5-azacitidine (5-7 days) between 2021 and 2024. The cohort included patients from four German academic centers all treated in first line. Outcome measures included bone marrow response, transfusion dependence, overall survival (OS) and progression-free survival (PFS). Median age was 73.5 years, with 70% of patients having secondary AML. Adverse molecular risk was observed in 75% of patients. The overall response rate (ORR) was 100%, with a composite complete remission rate of 78%. No significant differences in response rates were observed between the 7-day and 14-day venetoclax regimens. Median OS for the cohort was 15 months. Infection-related complications were observed in 55% of patients, with severe sepsis in 20% of cases. In this cohort, shortened venetoclax regimens demonstrated efficacy comparable to standard treatment protocols, with a potential reduction in hematologic toxicity. These findings support the individualization of treatment regimens to optimize clinical outcomes while potentially minimizing adverse effects.

Establishment of a Diamond-Blackfan anemia like model in zebrafish.

Anemia is defined as a lack of erythrocytes, low hemoglobin levels, or abnormal erythrocyte morphology. Diamond-Blackfan anemia (DBA) is a rare and severe congenital hypoplastic anemia that occurs due to the dominant inheritance of a ribosomal protein gene mutation. Even rarer is a case described as Diamond-Blackfan anemia like (DBAL), which occurs due to a loss-of-function EPO mutation recessive inheritance. The effective cures for DBAL are bone marrow transfusion and treatment with erythropoiesis-stimulating agents (ESAs). To effectively manage the condition, construction of DBAL models to identify new medical methods or screen drugs are necessary. Here, an epoa-deficient mutant zebrafish called epoaszy8 was generated to model DBAL. The epoa-deficiency in zebrafish caused developmental defects in erythroid cells, leading to severe congenital anemia. Using the DBAL model, we validated a loss-of-function EPO mutation using an in vivo functional analysis and explored the ability of ESAs to alleviate congenital anemia. Together, our study demonstrated that epoa deficiency in zebrafish leads to a phenotype resembling DBAL. The DBAL zebrafish model was found to be beneficial for the in vivo assessment of patient-derived EPO variants with unclear implications and for devising potential therapeutic approaches for DBAL.

Traditional Drugs Originating from Selected Medicinal Plants: An Intervention for Anaemia

Background: Anaemia is the most common disease that affects mostly females and children and is most prevalent in developing countries. Among various causes sickle cell anaemia is one of them, which is a cause of concern. Sickle Cell Disease (SCD) causes problems like blockage of blood flow, causing pain, and fatigue and also leads to death. Objective: With the advancement in science, diseases that were once considered unable to cure can be stopped or prevented and, in some cases, also be cured. As current therapies for the treatment of sickle cell anaemia are limited, like blood transfusions, bone marrow transfusions, etc., a non-surgical method where plant extracts or compounds were found effective in stopping, preventing, and in some cases reversal of SCD. In this review, we tried to gather information about those plants and compounds. Method: Numerous surveys in the literature were performed to determine the plants which have shown their potential against SCD. Relevant peer-reviewed publications were searched through various databases such as ScienceDirect, PubMed, Google Scholar, Research Gate, etc. Results: A total of more than 50 medicinal plants such as Acacia catechu, Alchornea cordifolia, Anchomanes difformis, Khayase negalensis, Terminalia catappa, etc., have been identified based on their potential against SCD, and 15 compounds such as Butylurea, Glyceraldehyde, Potassium cyanate, urea, etc., have also been identified which could work against SCD. These plants acting on sickle cell anemia on various pathways are also discussed. Conclusion: In this review, an approach was made to study those plants which have an effect against SCD, with proper mechanisms and compounds that show potency against this disease. So that better treatment options could be available for future generations.

Analysis of Key Indicators of Research, Development, and Innovation in Blood Establishments and Their Impact on the Delivery of Improved Quality Health Products and Services

Background and Objectives: The contribution of blood establishments (BEs) on Research, Development, and Innovation (R + D + I) is minimally addressed in the literature. Herein, we present an analysis of key indicators of R + D + I in BEs and discuss the impact of their R + D + I interests and priority areas, resources, and outcomes on the delivery of quality health products and services. Methods: Data from a worldwide representation of BEs were collected and analyzed in 2020. We assessed R + D + I areas studied, budget allocations, collaborations with other institutes, number of research staff available, and scientific production of BEs. Results: Details of 15 BEs from four continents were included in the study. All of them conducted R + D + I on a better understanding of their products and product safety. Other areas focused on were donors and donations (87%), bone marrow transplantation (80%), transfusion practices (80%), and immunogenetics (80%). 1%–11% (median of two points five %) of staff and 35–238 (median of 70, n = seven) in number, were involved in R + D + I. In 2018–2019, the budget allocated for R + D + I varied from € two point 6 to €13.7 million (median €seven point 6 million, n = 8) and it was zero point eight–10.5% (median of two points one %) of the total budget of BEs. Twelve (80%) and 11 (73%) BEs collaborated with academic institutes and hospitals, respectively. All centers generated publications and conference presentations, whereas only 4 (27%) hold patents. Conclusion: Research is an essential component in BEs that further potentiates R + D + I by partnering with research centers and universities as well as establishing specialized networks. A strong commitment to allocate resources and establish dedicated facilities or strategic alliances may generate world-class innovations in this ever-growing field.

Intraosseous infusion of liposome-encapsulated hemoglobin (HbV) acutely prevents hemorrhagic anemia-induced lethal arrhythmias, and its efficacy persists with preventing proarrhythmic side effects in the subacute phase of severe hemodilution model.

Artificial oxygen carriers (HbV) can treat hemorrhagic shock with lethal arrhythmias (VT/VF). No reports exist on subacute HbV's effects. Acute and subacute resuscitation effects with anti-arrhythmogenesis of HbV were studied in 85% blood exchange rat model (85%-Model). Lethal 85%-Model was created by bone marrow transfusion and femoral artery bleeding in 80 SD rats in HbV-administered group (HbV-group), washed erythrocyte-administered group (wRBC-group), and 5% albumin-administered group (ALB-group). Survival rates, anti-arrhythmic efficacy by optical mapping system (OMP) with electrophysiological study (EPS) in Langendorff heart, cardiac autonomic activity by heart rate variability (HRV) and ventricular arrhythmias by 24-h electrocardiogram telemetry monitoring (24h-ECG) in awake, and left ventricular function by echocardiography (left ventricular ejection fraction [LVEF]) were measured. All rats in HbV- and wRBC-groups survived for 4 weeks, whereas no rats in ALB-group. HbV and wRBC acutely suppressed VT/VF in Langendorff heart through ameliorating action potential duration dispersion (APDd) analyzed by OMP with EPS. For subacute analysis, 50% blood exchange by 5% albumin was used (ALB-group 50). Subacute salutary effect on APDd and VT/VF inducibility was confirmed in HbV- and wRBC-groups. 24h-ECG showed that HbV and wRBC suppressed none-sustained ventricular tachycardia (NSVT) and sympathetic component of HRV (LF/HF) with preserved LVEF (HbV-group, wRBC-group vs. ALB-group 50; NSVT numbers/days, 0.5±0.3, 0.4±0.3 vs. 3.9±1.2*; LF/HF, 1.1±0.2, 0.8±0.2 vs. 3.5±1.0*; LVEF, 84±5, 83±4, vs. 77±4%*; *p<0.05). Collectively, HbV has sustained antiarrhythmic effect in subacute 85%-Model by ameliorating electrical remodeling and improving arrhythmogenic modifying factors (HRV and LVEF). These findings are useful in now continuing clinical trials of HbV.

Predictors for Improvement in Patient-Reported Outcomes: Post-Hoc Analysis of a Phase 3 Randomized, Open-Label Study of Eculizumab and Ravulizumab in Complement Inhibitor-Naïve Patients with Paroxysmal Nocturnal Hemoglobinuria (PNH)

Predictors for Improvement in Patient-Reported Outcomes: Post-Hoc Analysis of a Phase 3 Randomized, Open-Label Study of Eculizumab and Ravulizumab in Complement Inhibitor-Naïve Patients with Paroxysmal Nocturnal Hemoglobinuria (PNH)

Gaining a Better “Sense” for ASXL1 Mutations in Myelofibrosis: Assessing the Variable Impact of Frameshift, Nonsense, and Missense Mutations

Introduction: ASXL1 gene mutations commonly occur in myeloid diseases and are associated with inferior prognoses. They can occur as frameshift, nonsense or missense mutations. In myelofibrosis (MF) specifically, ASXL1 mutations are associated with worse overall survival (OS) and leukemia-free survival (LFS). While the general impact of ASXL1 mutations has been well-studied, the variable impact based on type of mutation is less clear. In CMML and MDS, frameshift and nonsense mutations correlate with shorter survival and increased risk of leukemic transformation. In this study, we aimed to analyze the role of ASXL1 mutations in MF while stratifying for type of mutation.Methods: We retrospectively analyzed MF patients seen at our institution who had next-generation sequencing (NGS) performed as part of routine clinical care between 9/1/2013 and 5/1/2017. Laboratory and clinical parameters calculated from first presentation. OS defined from time of NGS assessment.Results: We evaluated 182 MF patients with available molecular profiling. ASXL1 mutations were present in 71 (39%) patients. Among ASXL1 mutations, 44 were frameshift (FS) mutations (62%), 14 were nonsense (NS) mutations (20%) and 13 were missense (MS) mutations (18%). Demographic and clinical features of these groups can be seen in figure 1. Grouped together, ASXL1 mutations were associated with high-risk clinical features such as decreased hemoglobin (p = 0.003), decreased platelet count (p = 0.01), increased bone marrow fibrosis (p = 0.02), transfusion dependence (p = 0.005), increased LDH (p = 0.02), and higher MF-specific prognostic scores (IPSS, DIPSS, and DIPSS+) (p < 0.001, p < 0.001, p = 0.003, respectively). Excluding MS mutations, the correlation with high-risk features was strengthened and new correlations between ASXL1 mutations and leukocytosis (p = 0.006), monocytosis (p = 0.02), and the presence of EZH2 (p = 0.04), NRAS (p = 0.008), and SRSF2 (p = 0.01) mutations emerged. ASXL1 NS mutations were associated with presence of splenomegaly (p = 0.01), increased immature myeloid cells (p = 0.03), and high IPSS (p = 0.04) and DIPSS (p = 0.04) scores when compared to ASXL1 wild-type (WT) patients. ASXL1 MS mutations correlated with decreased hemoglobin (p = 0.03) and decreased bone marrow cellularity (p = 0.007), but did not correlate with prognostic scores.High molecular risk (HMR) mutations (SRSF2, EZH2, IDH1/2) occurred more commonly with ASXL1 FS mutations than with ASXL1 MS mutations (p = 0.003) or ASXL1 WT (p = 0.002). SRSF2 mutations occurred more commonly in patients with ASXL1 FS mutations compared to ASXL1 MS mutations (p = 0.02) and ASXL1 WT (p = 0.03). EZH2 mutations occurred more commonly with ASXL1 FS mutations than with ASXL1 WT (p = 0.02).Including all ASXL1 mutations, there was a trend towards inferior LFS (p = 0.12) when compared to ASXL1 WT. Excluding NS and MS mutations, ASXL1 FS mutations were associated with decreased LFS (p = 0.02). The rate of transformation to blast-crisis was 14% with FS mutations, 0% with NS and MS mutations, and 4% in ASXL1 WT patients. ASXL1 mutations were associated with inferior OS (p = 0.005). When assessed by type of mutation, only FS mutations were associated with inferior OS (p = 0.003). NS mutations were not associated with OS (p = 0.39).Conclusion: The impact of ASXL1 mutations on clinical phenotype and outcome is most clearly demonstrated with frameshift mutations. Nonsense mutations appear clinically significant given their correlation with phenotype and higher-risk disease, but their impact on survival is less clear. Missense mutations do not have an apparent impact in MF. Increased presence of additional high-risk mutations in patients with ASXL1 frameshift mutations suggests a more unstable genome and likely contribute to inferior outcomes. [Display omitted] DisclosuresSallman:Celgene: Research Funding. Padron:Incyte: Honoraria, Research Funding. Lancet:Pfizer: Other: Institutional research funding; Biopath, Biosight, Boehringer Ingelheim, Celator/Jazz, Celgene, Janssen, Karyopharm Therapeutics, and Novartis: Consultancy. Komrokji:Celgene: Honoraria; Novartis: Honoraria, Speakers Bureau.

Brucellosis in transplant recipients: A systematic review.

Brucellosis is a bacterial disease caused by Brucella species. The purpose of this study was to evaluate brucellosis in all types of transplant patients. All the cases of brucellosis in transplant patients with no time and language limitations were searched and retrieved on May 20, 2020, using the following search keywords: (Brucella OR Brucellosis) AND (Transplant OR Transplantation) through the following medical databases: Web of Sciences, Google Scholar, Scopus, PubMed, and regional databases, for example, SID. All clinical features, including the time of transmission (before, during, and after transplantation), treatment protocols and medications, and patients' outcomes were investigated. A total of 14 cases reported in 14 studies (out of 777 studies) were retrieved. Kidney (50%), liver (28.5%), and hematopoietic stem cell transplantation (14.2%) were the most reported types of transplantation. The presentation of brucellosis in 42.8% of the patients occurred in the early post-transplantation period, whereas 57.1% of the cases presented with late onset disease. Brucellosis in transplant recipients seems to be uncommon even in the endemic regions. However, rare cases could be transmitted through bone marrow transplantation and transfusion. Precise screening and meticulous supervision during and after transplantation might lead to a reduction in the frequency of brucellosis.

Clinical observations of bone marrow transfusion for promoting bone marrow reconstruction after chemotherapy for AIDS-related lymphoma

BackgroundThis study investigates the effect of autologous bone marrow transfusion (BMT) on the reconstruction of both bone marrow and the immune system in patients with AIDS-related lymphoma (ARL).MethodsA total of 32 patients with ARL participated in this study. Among them, 16 participants were treated with conventional surgery and chemotherapy (control group) and the remaining 16 patients were treated with chemotherapy followed by autologous bone marrow transfusion via a mesenteric vein (8 patients, ABM-MVI group) or a peripheral vein (8 patients, ABM-PI group). Subsequently, peripheral blood and lymphocyte data subsets were detected and documented in all patients.ResultsBefore chemotherapy, no significant difference in indicators was observed between three groups of ARL patients. Unexpectedly, 2 weeks after the end of 6 courses of chemotherapy, the ABM-MVI group, and the ABM-PI group yielded an increased level of CD8+T lymphocytes, white blood cells (WBC), and platelet (PLT) in peripheral blood in comparison to the control group. Notably, the number of CD4+T lymphocytes in the ABM-PI group was significantly higher than that in the other two groups. Additionally, no significant difference in haemoglobin levels was observed before and after chemotherapy in both the ABM-MVI and ABM-PI groups, while haemoglobin levels in the control group decreased significantly following chemotherapy.ConclusionsAutologous bone marrow transfusion after chemotherapy can promote the reconstruction of both bone marrow and the immune system. There was no significant difference in bone marrow recovery and reconstruction between the mesenteric vein transfusion group and the peripheral vein transfusion group.

Development and implementation of an evidence-based malignant hematology clinical pathway program.

304 Background: Clinical pathways provide a means to maximize value-based care for cancer patients. They have been associated with decreased costs and outcome improvements. Our institution entered a transformative partnership with an NCI designated comprehensive cancer center for the treatment of hematologic malignancies. As part of the collaboration, a multidisciplinary task force was established to adapt clinical pathways within our system. Given the multiple new drug approvals for the treatment of Acute Myeloid Leukemia (AML), this was the first pathway created. Methods: The taskforce consisted of physicians, pharmacists, nurses, quality manager, and information technology staff. The group met weekly to draft algorithms in accordance with national guidelines, updated evidence and institutional preferences. Electronic Medical Record (EMR) treatment plans were reviewed in a secondary multidisciplinary workgroup and validated to ensure compliance with the AML pathway. When applicable, specific criteria for use were developed to aid in medication use optimization. The finalized pathway and treatment plans were presented and approved at our clinical standards committee meeting. A chart audit was performed one year after pathway implementation to assess adherence, with a goal of 80% or higher. The results were compared to an audit assessing adherence to best available clinical evidence for the year prior to implementation. Results: The group established a consensus on treatment, laboratory testing, and supportive care, including anti-emetic, anti-microbial, and tumor lysis syndrome (TLS) prophylaxis. Electronic order sets were created for bone marrow biopsies, transfusion support, TLS and febrile neutropenia. Thirty-two EMR treatment plans for AML were built and/or revised, while five were inactivated. A total of 88 patient charts were included in the pathway adherence audit (44 before and 44 after implementation). Pre and post pathway adherence was 64% and 89%, respectively (p=0.006). Deviations were categorized by type (table). Conclusions: AML pathway development and implementation resulted in standardization of treatment regimens, supportive care and higher adherence to institutional evidence based practices. [Table: see text]

AML-207: Glasdegib in Combination with Azacitidine in Patients with Untreated Higher-Risk Myelodysplastic Syndromes, Acute Myeloid Leukemia, and Chronic Myelomonocytic Leukemia: Effects on Marrow Recovery and Transfusion Independence

Context Glasdegib + azacitidine (AZA) showed promising remission rates and overall survival with a generally well-tolerated and manageable safety profile in an analysis of BRIGHT MDS & AML 1012 ( NCT02367456 ) in patients with higher-risk myelodysplastic syndromes (MDS), acute myeloid leukemia (AML), and chronic myelomonocytic leukemia (CMML). Objective Here, we evaluate early hematopoietic recovery and transfusion independence with glasdegib + AZA in BRIGHT MDS & AML 1012. Design Phase 1b, open-label study. Data cut-off: September 11, 2019. Setting Multicenter study at centers in Europe and North America. Patients Untreated patients with AML, higher-risk MDS, and CMML ineligible for intensive chemotherapy received glasdegib + AZA. Interventions Glasdegib 100 mg QD; AZA 75 mg/m2/D on D1-7 q28D. Main outcome measures Here we report the recovery of absolute neutrophil count (ANC), hemoglobin, and platelets, as well as rates of transfusion. Results Among patients with MDS (n=30; including 3 with CMML), median duration of treatment was 5.0 months (range, 0.4–15.5). Recovery occurred as early as Cycle 1 for ANC (≥1000/μL, 57%; ≥500/μL, 75%), hemoglobin (≥10 g/dL, 31%; ≥9 g/dL, 62%) and platelets (≥100,000/μL, 59%; ≥50,000/μL, 83%). Early platelet recovery correlated with response to treatment; 54% (7/13) of patients with platelets ≥ 100,000/μL at Cycle 2, D1 achieved complete or partial remission vs 0% (0/13) of patients with Conclusions Glasdegib + AZA shows promising rates of survival with early marrow recovery in the up-front treatment of patients with MDS, AML and CMML ineligible for intensive chemotherapy. The association between hematopoietic recovery and efficacy in the MDS cohort merits further study. Sponsor Pfizer.

Glasdegib in combination with azacitidine (AZA) in patients (pts) with untreated higher-risk myelodysplastic syndromes (MDS), acute myeloid leukemia (AML) and chronic myelomonocytic leukemia (CMML): Effects on marrow recovery and transfusion independence.

7526 Background: Glasdegib, an oral inhibitor of the Hedgehog signaling pathway, is approved in the USA in combination with low-dose cytarabine to treat pts with newly diagnosed AML unable to receive intensive chemotherapy due to comorbidities or age (≥75 years). Glasdegib + AZA showed promising remission rates and overall survival with a generally well-tolerated and manageable safety profile in an analysis of BRIGHT MDS &amp; AML 1012 in pts with MDS, AML and CMML. Here we evaluate early hematopoietic recovery and transfusion independence with glasdegib + AZA in this ongoing Phase Ib study. Methods: Untreated pts with MDS, AML and CMML ineligible for intensive chemotherapy received glasdegib (100 mg QD) + AZA (75 mg/m2/D on D1–7 q28D). Data cutoff: Sept 11, 2019. Results: Among pts with MDS (n=30; including 3 with CMML), median duration of treatment was 5.0 months (range, 0.4–15.5). Recovery of absolute neutrophil count (ANC), hemoglobin (Hb) and platelets at 2 thresholds started in cycle (Cyc) 1 (Table). Early platelet recovery correlated with response to treatment; 54% (7/13) of pts with platelets ≥100,000/µL at Cyc 2, D1 achieved complete or partial remission vs 0% (0/13) of pts with &lt;100,000/µL, P=0.002. Start of Cyc 2 was delayed due to AEs in 8% (2/26) of pts. 54% (7/13) of evaluable pts transfusion dependent at baseline (BL) became transfusion independent. Among pts with AML (n=30), median duration of treatment was 5.0 months (range, 0.3–14.9). ANC, Hb and platelet recoveries started in Cyc 1 (Table). 9% (2/23) of pts had Cyc 2 dose delays due to AEs. 64% (9/14) of evaluable pts transfusion dependent at BL became transfusion independent. Clinical trial information: NCT02367456 . Conclusions: Glasdegib + AZA shows promising rates of survival with early marrow recovery in the up-front treatment of pts with MDS, AML and CMML ineligible for intensive chemotherapy. The association between early hematopoietic recovery and efficacy in the MDS cohort merits further study. [Table: see text]

Sterility monitoring of cat stored donor blood

Abstract. Contamination of donor blood is a permanent risk factor for blood transfusion. Using of non-sterile blood products can leads to severe complications and high health risks for recipient animals. Sterility research of canned blood, its components, canned bone marrow and blood transfusion products is required to detect possible contamination of aerobic and anaerobic microorganisms. Factors of donor blood bacterial contamination may be blood collection systems, non-compliance of aseptic rules during blood collection, tightness violation of container, and others. As closed blood collection systems are not always available to veterinary practitioners, semi-closed systems or open (direct) blood collection are an alternative, which are at high risk for bacterial contamination of donor blood when used carelessly. In our research, 12 canned cat donor blood samples were analyzed in total. Samples were stored for 30 days at +2-6 °C. The donor animals were clinically healthy 12 cats. Blood was collected from the jugular vein by semi-closed systems in polymeric containers with CPDA anticoagulant. The bacterial culture method is considered as the gold standard for assessing the presence of blood contamination in most blood transfusion centers. The tested blood samples were inoculated into thioglycolate and Sabouraud medium and incubated in a thermostat at 20-25 °C. The incubation period was 14 days. According to the results of bacteriological examination of donor blood samples after their storage – non-sterile samples were not detected. Thereby, semi-closed blood collection systems are reliable and allow to obtain donor blood samples without losing its sterility in long-term storage. Keywords: animals blood transfusion, cat donor blood, microbial contamination, donor blood sterility

Nix-mediated mitophagy regulates platelet activation and life span

AbstractPlatelet activation requires fully functional mitochondria, which provide a vital energy source and control the life span of platelets. Previous reports have shown that both general autophagy and selective mitophagy are critical for platelet function. However, the underlying mechanisms remain incompletely understood. Here, we show that Nix, a previously characterized mitophagy receptor that plays a role in red blood cell maturation, also mediates mitophagy in platelets. Genetic ablation of Nix impairs mitochondrial quality, platelet activation, and FeCl3-induced carotid arterial thrombosis without affecting the expression of platelet glycoproteins (GPs) such as GPIb, GPVI, and αIIbβ3. Metabolic analysis revealed decreased mitochondrial membrane potential, enhanced mitochondrial reactive oxygen species level, diminished oxygen consumption rate, and compromised adenosine triphosphate production in Nix−/− platelets. Transplantation of wild-type (WT) bone marrow cells or transfusion of WT platelets into Nix-deficient mice rescued defects in platelet function and thrombosis, suggesting a platelet-autonomous role (acting on platelets, but not other cells) of Nix in platelet activation. Interestingly, loss of Nix increases the life span of platelets in vivo, likely through preventing autophagic degradation of the mitochondrial protein Bcl-xL. Collectively, our findings reveal a novel mechanistic link between Nix-mediated mitophagy, platelet life span, and platelet physiopathology. Our work suggests that targeting platelet mitophagy Nix might provide new antithrombotic strategies.

Fibrotic liver microenvironment promotes Dll4 and SDF-1-dependent T-cell lineage development

The reconstitution of the T-cell repertoire and quantity is a major challenge in the clinical management of HIV infection/AIDS, cancer, and aging-associated diseases. We previously showed that autologous bone marrow transfusion (BMT) via the hepatic portal vein could effectively restore CD4+ T-cell count in AIDS patients also suffering from decompensated liver cirrhosis. In the current study, we characterized T-cell reconstitution in a mouse model of liver fibrosis induced by CCl4 and found that T-cell reconstitution after BMT via hepatic portal vein was also greatly enhanced. The expression of Dll4 (Delta-like 4), which plays an important role in T-cell progenitor expansion, was elevated in hepatocytes of fibrotic livers when compared to normal livers. This upregulation of Dll4 expression was found to be induced by TNFα in an NFκB-dependent manner. Liver fibroblasts transfected with Dll4 (LF-Dll4) also gained the capacity to promote T-cell lineage development from hematopoietic stem cells (HSCs), resulting in the generation of DN2 (CD4 and CD8 DN 2) and DN3 T-cell progenitors in vitro, which underwent a normal maturation program when adoptively transferred into Rag-2 deficient hosts. We also demonstrated a pivotal role of SDF-1 produced by primary liver fibroblasts (primary LF) in T-lineage differentiation from HSCs. These results suggest that Dll4 and SDF-1 in fibrotic liver microenvironment could promote extrathymic T-cell lineage development. These results expand our knowledge of T-cell development and reconstitution under pathological conditions.

A clinical study of haploidentical hematopoietic stem cell transplantation in the treatment of pediatric patients with acquired severe aplastic anemia: single center experience

目的探讨单倍型造血干细胞移植（haplo-HSCT）治疗儿童获得性重型再生障碍性贫血（SAA）的疗效。方法回顾性分析2011年12月1日至2017年12月1日接受haplo-HSCT的59例SAA患者。结果①全部59例SAA患儿中男37例、女22例，中位年龄4.5（1.2~14.8）岁，中位体重43（12~80）kg；SAA-Ⅰ型47例，SAA-Ⅱ型12例，26例为极重型再生障碍性贫血（VSAA）；首次移植56例，二次移植3例。②预处理选用白消安+环磷酰胺+抗胸腺细胞球蛋白（ATG）方案或白消安+氟达拉滨+环磷酰胺+ATG方案；采用环孢素A（CsA）+霉酚酸酯+甲氨蝶呤方案预防急性GVHD；回输单个核细胞中位数为15.60（7.74~21.04）×108/kg，CD34+细胞中位数为4.86（3.74~7.14）×106/kg。③全部59例患儿均获得中性粒细胞和血小板植入。中性粒细胞植入中位时间为13（10~19）d，血小板植入中位时间为19（9~62）d。④Ⅰ~Ⅱ、Ⅲ/Ⅳ度急性GVHD发生率分别为45.76%（27/59）、13.56%（8/59），慢性GVHD发生率为8.47%（5/59）。巨细胞病毒血症发生率为59.32%（35/59）、EB病毒血症发生率为28.81%（17/59）。⑤中位随访时间30（8~80）个月，57例无病存活，2例死亡（均死于GVHD），5年总生存率、无失败生存率均为（96.4±2.5）%。结论haplo-HSCT是儿童SAA疗效较好的治疗方法。

Amalgamation of Stem Cells with Nanotechnology: A Unique Therapeutic Approach.

In the last few years, the stem cell therapy has gained much popularity among researchers and scientists of biomedical field. It became an effective and alternative approach for the treatment of various physiological conditions (like accidental injuries, burn damage, organ failure, bone marrow transfusion, etc.) and chronic disorders (diabetes, cancer, neurodegenerative disorders, periodontal diseases, etc.). Due to the unique ability of cellular differentiation and regeneration, stem cell therapy serves as the last hope for various incurable conditions and severe damages. The amalgamation of stem cell therapy with nanotechnology brings new prospects to the stem cell research, as it improves the specificity of the treatment and controls the stem cell proliferation and differentiation. In this review article, we have discussed various nanocarrier systems such as carbon nanotubes, quantum dots, nanofibers, nanoparticles, nanodiamonds, nanoparticle scaffold, etc. utilized for the delivery of stem cell inside the body.

Development of a Hematology-Specific Fellowship Curriculum for Advanced Practice Providers Utilizing a Needs-Based Assessment

Background: As our healthcare system faces increasing complexity, it is important for all healthcare providers to practice at the full scope of their training. However, there are limited current options for subspecialty training in hematology for advanced practice providers (APPs), a group of health care providers including both nurse practitioners and physician assistants. We are unaware of any existing postgraduate fellowship for APPs focused on education in both malignant and nonmalignant hematologic disorders. We hope that by creation of the first such fellowship, we can better prepare APP graduates with the subspecialty-specific knowledge required to become highly skilled and competent clinicians in hematology.Methods: Using surveyhero.com, we conducted a web-based needs assessment survey which was distributed to 68 APPs currently working in the hematology and blood & marrow transplant (BMT) teams at three Mayo Clinic sites (Rochester, Scottsdale, and Jacksonville). This survey included questions regarding hematology-specific education the respondents had received in their APP schools, as a way to assess participant's perceptions about the readiness to practice in hematology after completion of APP education, and to identify the learning/training needs that are most important for APPs to practice in hematology.Results: Of 68 APPs, 49 (72%; 34 NPs,15 PAs) completed the survey. 57% of respondents were new APP graduates when hired and 35% had no prior work experience in hematology/BMT. All APPs held a Master's or higher degree (doctorate 31%). Thirty-nine (80%) reported <5% of their APP school curriculum was hematology-focused. The majority (92%) felt that the level of subspecialty training they received in APP schools did not adequately prepare them with the full confidence to practice in hematology. Forty-four (90%) APPs believed subspecialty training could help them to become more competent providers for patients with hematologic disorders. Forty-seven (96%) APPs agreed that being confident and knowledgeable in their practice positively impacted their job satisfaction, and most APPs (84%) felt structured hematology training would attract them to stay within the specialty. The educational subjects that APPs identified as most important included variety of malignant and benign hematologic disorders as well as hematopathology, bone marrow transplant, palliative care, transfusion medicine, infectious disease and pharmacology related to hematology practice. The top three effective learning strategies reported by the APP respondents were active learning from direct patient care, cased based teaching, and educational experience during hospital rounds.Conclusions and Discussions: This needs-based assessment educational project revealed to us the significant gaps in subspecialty training of APP education in hematology and confirmed the necessity of this fellowship. The findings of the survey helped us to optimize the fellowship curriculum in order to meet the learning needs of future APP trainees. Development of the subspecialty fellowship program is a step forward in the future training of APPs. We believe our fellowship has the potential to serve as the postgraduate training model for other institutions nationwide. DisclosuresLacy:Celgene: Research Funding.

The Effects of Filgrastim on Complications of Patients with Cerebral Hemorrhage Due To Head Trauma.

BACKGROUND:Filgrastim, a neopogen brand, is a blood-forming agent and a natural protein in the body that plays a role in stimulating the growth of white blood cells and protecting them against infectious agents. To the best of knowledge, human and animal specimens have shown the effect of Filgrastim on treating brain injuries regarding bone marrow transfusion into the blood, neuroprotection, stimulation of neurons for forming new neural networks and reducing the risk of bacterial infections.AIM:This study aimed to investigate the effect of Filgrastim on the prognosis of a cerebral haemorrhage in patients with traumatic brain injury.METHODS:This study was conducted as a clinical trial, in which the initial diagnosis of patients with cerebral haemorrhage due to head trauma was performed with a clinical examination and CT scan. After the patient arrives at the emergency room, the patient’s initial examination is performed, and blood tests are taken from the patient. Moreover, CBC values (Hb, Platelet, Hematocrit) were checked and recorded in the checklist. The intervention group received 150 mcg/day Filgrastim injected subcutaneously for 4 days. Furthermore, patients in the control group received the same amount of sterile water. At the end of the treatment period, blood tests were performed again in all patients, and their results were then recorded. All data were analysed by SPSS v.21 software package.RESULTS:Our findings revealed that the mean volume of bleeding in the intervention group based on CT scan was significantly reduced after four days as compared to the control group. Moreover, the mean score of consciousness and muscular strength of patients in the intervention group was significantly higher than the control group. Also, WBCs in the intervention group exhibited a significant increase after four days of intervention, while platelet and hematocrit levels in the intervention group decreased significantly compared to the control group.CONCLUSION:Regarding the results, the therapeutic application of filtration is considered to be effective. Given the lack of serious complications of the proposed dosages, the use of this drug can be suggested.

Repeated Autologous Bone Marrow Transfusion through Portal Vein for Treating Decompensated Liver Cirrhosis after Splenectomy.

Objective This study is aimed at examining the impact of repeated intraportal autologous bone marrow transfusion (ABMT) in patients with decompensated liver cirrhosis after splenectomy. Methods A total of 25 patients with decompensated liver cirrhosis undergoing splenectomy were divided into ABMT and control groups. The portal vein was cannulated intraoperatively using Celsite Implantofix through the right gastroomental vein. Both groups were given a routine medical treatment. Then, 18 mL of autologous bone marrow was transfused through the port in the patients of the ABMT group 1 week, 1 month, and 3 months after laminectomy, while nothing was given to the control group. All patients were monitored for adverse events. Liver function tests, including serum albumin (ALB), alanine aminotransferase (ALT), total bilirubin (TB), prothrombin activity (PTA), cholinesterase (CHE), α-fetoprotein (AFP), and liver stiffness measurement (LSM), were conducted before surgery and 1, 3, and 6 months after surgery. Results Significant improvements in ALB, ALT, and CHE levels and decreased LSM were observed in the ABMT group compared with those in the control group (P < 0.05). TB and PTA improved in both groups but with no significant differences between the groups. No significant changes were observed in AFP in the control group, but it decreased in the ABMT group. No major adverse effects were noted during the follow-up period in the patients of either group. Conclusions Repeated intraportal ABMT was clinically safe, and liver function of patients significantly improved. Therefore, this therapy has the potential to treat patients with decompensated liver cirrhosis after splenectomy. This trial was registered with the identification number of ChiCTR-ONC-17012592.