bluuebunny/crossref_metadata_2025_split huggingface dataset:
Allogeneic Hematopoietic Stem Cell Transplantation Of Patients With Wiskott-Aldrich Syndrome With Total Body Irradiation (TBI), Thiotepa and Fludarabine Or Cyclophosphamide Followed By T-Cell Depleted Grafts From Alternative Donors
Authors: Prockop Susan E. , Boulad Farid , Kernan Nancy A. , Khalif Ramzi , Kobos Rachel , Scaradavou Andromachi , O'Reilly Richard J. 
Published: October 2019

Wiskott-Aldrich syndrome (WAS) is a rare X-linked congenital immunodeficiency syndrome characterized by micro-thrombocytopenia, eczema, autoimmune syndromes and malignancies that are often fatal. Early hematopoietic stem cell transplant (HSCT) experience for patients with WAS from alternative donors was associated with poor outcome including a high rate of graft rejection. Since 1998 we have transplanted 13 patients with WAS with grafts from alternative donors. Specifically, 9 of these patients received T cell depleted transplants and are the focus of this abstract. Grafts were from matched unrelated donors (N=5) mismatched unrelated donors (N=2) mismatched related donors (N=2). Patient age at transplant ranged from 1.1-21.5 years (median 3.3). Cytoreduction included Hyperfractionated TBI with Thiotepa and Cyclophosphamide or Fludarabine (N=7) Busulfan with Melphalan and Fludarabine (N=1) Cyclophosphamide with Thiotepa and Fludarabine (N=1). Prior to 2002 no children under 24 months received TBI. Subsequently CNS shielding was used with TBI for patients under the age of 3. All patients received ATG for graft rejection prophylaxis. Six patients had previously undergone splenectomy. Stem cell grafts were Lectin/E rosette separated T cell depleted bone marrow (N=4) or Isolex/E rosette separated T-cell depleted PBSC (N=5). Eight patients engrafted with median neutrophil engraftment on day 12 (11 -16). One patient who received cytoreduction with Cyclophosphamide, Thiotepa and Fludarabine suffered primary graft failure, had autologous recovery and went on to receive a second transplant and is alive and well. All patients developed Grade I – II mucositis. One patient suffered an early toxic death after developing acute encephalopathy during cytoreduction with Busulfan (8mg/kg) Melphalan (140mg/m2) and Fludarabine (125mg/m2) and one other patient with a prior history of lymphoma had progression of lymphoma and early death post HSCT. One developed acute GvHD (Grade III GI). Three patients developed autoimmune disorders associated with mixed chimerism. All three patients had complete resolution of their autoimmune disease and two of these three patients reverted to full donor chimerism. With a post HSCT follow-up period of a median of 7.5 years (3-15 years) seven of these nine patients are alive and disease-free. In summary, T-cell depleted grafts appear to extend transplant as a treatment option for patients with WAS who are without matched related donors. Recent successful experience with T cell depletion following chemotherapy only regimens for other patient populations will provide a way to explore non-TBI based cytoreduction and T cell depletion as an approach for future patients.

Disclosures:
No relevant conflicts of interest to declare.
Donor Genotypes For Interleukin-17A Gene Single Nucleotide Polymorphisms (SNPs) Allow Anticipation Of Complications After HLA-Identical Allogeneic Stem Cell Transplantation (allo-SCT)
Authors: Buces Elena , Martínez-Laperche Carolina , González-Rivera Milagros , Bosch-Vizcaya A , Martin-Antonio Beatriz , Guillem Vicent , Nieto Jb , González M. , La Camara Rafael De , Brunet Salut , Jimenez-Velasco Antonio , Espigado Ildefonso , Vallejo Carlos , Sampol Antonia , Serrano David , Kwon Mi , Gayoso Jorge , Balsalobre Pascual , Urbano-Izpizua Alvaro , Solano Carlos , Gallardo David , Díez Martín José Luis , Buno Ismael 
Published: October 2019

Introduction
Graft versus host disease (GvHD) is the main cause of morbimortality after allogeneic stem cell transplantation (allo-SCT). Several single-nucleotide polymorphisms (SNPs) in in the promoter region of cytokine genes have shown to alter their expression and are therefore associated with donor-recipient alloreactivity and, ultimately, with SCT outcome. Interleukin 17 (IL-17) is secreted by CD4+ T-cells and has been implicated in the pathogenesis of various autoimmune diseases but its importance in SCT is not well-known.

Objective
To analyse the influence of IL-17A SNP genotypes on the risk and severity of GvHD and other complications after HLA-identical allo-SCT.

Patients and Methods
Genomic DNA obtained from peripheral blood samples belonging to 546 patients and their HLA-identical sibling donors (Table 1) included in the DNA Bank of the Spanish Group for Hematopoietic Stem Cell Transplantation (GETH). Genotyping of the polymorphisms of interest, rs8193036 (-737C>T), rs2275913 (-197G>A), rs3819024 (-444A>G), rs4711998 (-877A>G), were performed by multiplex primer extension followed by mass spectrometry (MALDI-TOF; Sequenom MassArray).

Results
Genotype frequencies are shown in Table 2 and the association between IL-17A genotypes and complications after allo-SCT are shown in Table 3. Patients transplanted from donors harboring genotype CC for the SNP rs8193036 show increased risk of grade III-IV acute GvHD (7/26 vs 47/397, p=0.035) and of grade II-IV acute GvHD (13/26 vs 133/409, p=0.048). Patients transplanted from donors harboring allele A in the SNP rs4711998 show increased risk of extensive chronic GvHD (53/161 vs 43/177, p=0.045). Relapse rate was not related with IL-17A SNP genotypes. Finally a higher risk of toxicity-related mortality (TRM) was observed in patients transplanted from donors harboring allele A for SNP rs2275913 (78/293 vs 46/227, p=0.048), donors harboring allele G for SNP rs3819024 (78/279 vs 46/242, p=0.011) and donors harboring allele A for SNP rs4711998 (68/250 vs 55/229, p=0.044).

Conclusions
IL-17A SNP genotyping might be useful to anticipate complications after sibling HLA-identical allo-SCT and, therefore, to improve the clinical management of transplanted patients. This results further support the idea of a genetic predisposition to certain complications after allo-SCT.
Paper presented on behalf of the GvHD/Immunotherapy committee of the Spanish Group for Hematopoietic Transplantation (GETH).

Disclosures:
No relevant conflicts of interest to declare.
Alpha 1 Antitrypsin, C Reactive Protein, and Hemolysis Markers: Association With Cytokines Profile In Sickle Cell Disease Patients In Steady-State and Crisis-State
Authors: Carvalho Magda , Boas Wendell Vilas , Veloso Cerqueira Bruno Antônio , Reis Joao Oliveira , Araujo Theo , Rocha Larissa , Luz Nivea , Lopes Valma , Borges Valeria , Goncalves Marilda Souza 
Published: October 2019

Introduction
Sickle cell disease (SCD) has a heterogeneous clinical picture, characterized by hemolysis, chronic inflammation and vaso-occlusive events and painful crisis.

Aims
Investigate the levels of Alpha 1 antitrypsin (A1AT), C reactive protein (CRP), hemolysis markers and its association with cytokines profile in SCD patients in steady-state and crisis-state.

Methods
It was developed a cross sectional study in a total of 72 SCD patients in steady-state (SP) and 23 SCD patients in crisis (CP) age-and-sex-matched. Hematological analysis was performed by automatic cell counter, hemoglobin profile by HPLC, and biochemistry analyses of inflammation and infection markers and lipid, hepatic, and kidney metabolism markers were investigated by immunochemistry assays. Plasma levels of TNFα, IFNγ, IL-10, IL-1β, IL-6 and IL-8 were measured using Cytometric Bead Array - CBA (BD Biosciences Pharmingen, USA) according to the manufacturer’s protocol.

Results
Statistical analysis showed that SCD steady-state patients group had the highest IL-12 concentration (p<0.0001) and there were a decrease in TNFα, IL-10, IL-1β, and IL-6 levels (p< 0.0001) when compared to CP group (figure 1). However, significant differences in IL-8 levels were not finding in the comparison between SCD in steady-state and crisis patients groups. Biomarkers analyses of SCD steady-state patients showed significant negative correlation between IL-8 with A1AT (r= -0.25; p= 0.03) and CRP (r= -0.24; p= 0.04) and significant positive correlation with lactate dehydrogenase (LDH) (r= 0.25; p= 0.03). The IL-6 showed significant positive correlation with white blood cell count (WBC) (r= 0.52; p< 0.0001), ferritin (r= 0.30; p= 0.001) and CRP (r= 0.42; p= 0.0002). TNFα showed a significant positive correlation with leukocyte count (r= 0.28; p= 0.02) and A1AT (r= 0.29; p= 0.01) and IL-10 showed a significant positive correlation with platelets count (r= 0.30; p= 0.01) and A1AT (r= 0.29; p= 0.01).

Conclusions
Immunological aspects of SCD patients have been increasingly studied. The high levels of Th2 cytokines (IL-6 and IL-10) and proinflammatory cytokines (TNFα and IL-1β) in SCD patients in crisis-state, possibly is related to severe clinical manifestations, despite the fundamental role of these cytokines in the pathophysiology is not yet completely clear. The correlation between these cytokines and biomarkers associated with important clinical manifestations in SCD, such as WBC, platelet count, A1AT and CRP, highlights the important role of inflammatory mediators in SCD and its possible association with an expression or activation of adhesion molecules in neutrophils and vascular endothelium.

Disclosures:
No relevant conflicts of interest to declare.
Psychological Factors Associated With Episodic Oral Chelation Adherence In Thalassaemia
Authors: Jane Vosper , Psy D Clin , Evangeli Michael , Psy D Clin , Porter John , Shah Farrukh 
Published: October 2019

Objectives
Beta-Thalassaemia-Major is a life-long genetic haemoglobin disorder where patients require intensive regimens, including frequent blood transfusions and daily chelation therapy. Despite the introduction of oral chelators, non-adherence continues to be prevalent. Understanding psychosocial correlates of chelation adherence is important when considering potential interventions to improve adherence as they may be potentially modifiable. Previous studies of the relationships between psychosocial factors and chelation adherence have neither been theory driven nor assessed theoretically important variables such as self-efficacy and outcome expectancies. In addition, there has been little investigation of situational determinants of adherence (cognitive, behavioural or affective). This study, informed by the Health Action Process Approach, investigated within-participant correlates of oral chelation adherence on a daily (episodic) basis.

Design
The study used a within-participant cross sectional design. Thirty seven adult participants with Beta-Thalassaemia Major were recruited from clinics at two hospitals, of which 31 were able to identify an adherent and non-adherent episode within the last two months. Sampling was systematic.

Main outcome measures
A structured interview was developed to assess cognitive, behavioural and affective situational variables related to recent adherent and non-adherent episodes. The main cognitive variables (situational self-efficacy and outcome expectancies) were derived from The Health Action Process Approach (HAPA). Behavioural situation variables included substance use, day of the week, activity, location, access to medication, reminder cues and social context. Affective situational variables were mood and bodily pain.

Results
Positive outcome expectancies and higher self-efficacy together significantly predicted adherent episodes (p<0.001), however, only self-efficacy independently predicted adherent episodes (β=-.0.26, SE=0.11, p=0.018). This relationship persisted when potentially confounding behavioural factors were controlled (difficulty in accessing medication, location and whether alone) (See Table 1).

Conclusion
Findings were consistent with the HAPA and suggested the importance of situational cognitive factors, particularly self-efficacy, to chelation adherence. These findings add to the evidence of the effect of self-efficacy on medication adherence across medical conditions and extend previous work in emphasising situational variation in self-efficacy. Adherence interventions should consider situational variables (cognitive and behavioural) that are potentially modifiable.

Disclosures:
No relevant conflicts of interest to declare.
Regional Myocardial Contractility In Thalassemia Major By Magnetic Resonance Tagging
Authors: Meloni Antonella , Tudisca Chiara , Grassedonio Emanuele , Izzi Giancarlo , Lendini Maddalena , Biguzzi Rino , Filati Graziella , Maggio Aurelio , Marinelli Martina , Midiri Massimo , Lombardi Massimo , Pepe Alessia 
Published: October 2019

Introduction
Magnetic resonance (MR) tagging analyzed by dedicated tracking algorithms allows very precise measurements of myocardial motion and characterization of regional myocardial function. No extensive data are available in literature. Our aim was to quantitatively assess for the regional myocardial contractility in thalassemia major (TM) patients and to correlate it with heart iron overload and global biventricular function.

Methods
Seventy-four TM patients (46 F; 31.8 ± 8.5 yrs) enrolled in the MIOT (Myocardial Iron Overload in Thalassemia) network underwent MR (1.5T). Three short-axis (basal, medial and apical) tagged MR images were analyzed off-line using harmonic phase (HARP) methods (Diagnosoft software) and the circumferential shortening (Ecc) was evaluated for all the 16 myocardial segments. Four main circumferential regions (anterior, septal, inferior, and lateral) were defined. The same axes were acquired by a T2* GRE multiecho technique to assess myocardial iron overload (MIO). Biventricular function parameters were quantitatively evaluated by cine images.

Results
Segmental ECC values ranged from -9.66 ± 4.17 % (basal anteroseptal segment) to 13.36 ± 4.57 % (mid-anterior segment). No significant circumferential variability was detected.
Compared with previous studied healthy subjects, TM patients showed strain values significantly lower in all the circumferential regions at each level (mean difference from 4 % to 13 %; P<0.001 for all the comparisons).
Segmental Ecc values were not significantly correlated with the correspondent T2* values and no correlation was detected considering the global values, averaged over all segmental values. Three groups identified on the basis of cardiac iron distribution: no MIO, heterogenous MIO and homogeneous MIO. The global ECC was comparable among the three groups (-11.56 ± 1.60 % vs -11.70 ± 2.43 % vs -11.14 ± 1.95 %; P=0.602).
Global ECC values were not significantly correlated with age and were comparable between the sexes.
Circumferential shortening was not associated to left ventricular (LV) volumes and ejection fraction (with a P>0.5 in all the comparisons).

Conclusions
TM patients showed a significantly lower cardiac contractility compared with healthy subjects, but this altered contractility was not related to cardiac iron, volumes and function.

Disclosures:
No relevant conflicts of interest to declare.
Monocytosis Correlated With Acute Alcoholic Hepatitis: A Case Report and Literature Review
Authors: Shi Qi , Thomas Lisa 
Published: October 2019

Introduction
Alcohol is a most frequent cause of liver disease in western countries. Alcoholic hepatitis is observed in approximately 20% of heavy drinkers. Acute alcoholic hepatitis (AH) is associated with mortality as high as 50%.Up to 40% of patient with severe alcoholic hepatitis die within 6 months after the onset of the clinical syndrome. Identifying individuals with a high mortality risk is crucial in the management of acute alcoholic hepatitis. We observed a patients with acute alcoholic hepatitis tend to have an increased level of monocytes.

Case presentation
47-year-old male with a significant history of alcohol abuse for 30 years presented with confusion, generalized shaking, and tremors for 4 days was admitted to the hospital. The patient was hospitalized 6 months ago for acute alcoholic hepatitis. Physical examination: Bp 140/80mmHg, Ultrasound of Abdomen showed hepatomegaly with enlarged liver measuring 19.1 cm in the midclavicular line and hepatic steatosis and gallbladder sludge without evidence of wall thickening or pericystic fluid. CT of abdomen Suspected fatty infiltration of the liver. Patient had ammonia level of 56 -58. His MELD score was between 52 in which the alcoholic hepatitis was diagnosed. The patient was treated with Ativan, Chlordiazepoxide, Thiamine, folic acid, Mulativitamin, and lactulose. After patient was treated for 7 days, Symptoms had been well controlled, and all of tests went to back normal range. Table1 shows clinical data of current and previous admission.

Discussion
Alcoholics develop acute hepatitis as an inflammatory reaction to the cells affected by fatty change. Diagnosis of alcoholic hepatitis based on clinical symptoms and laboratory finding alone including elevated AST/ALT (but may < 300 IU/mL), AST>ALT of 2, Total serum bilirubin > 5mg/deciliter, elevated INR, thrombocytopenia, and hypoalbuminimia, (cirrhosis). Leukocytosis with neutophilic predominance has been reported to correlates with degree of injury. As a feature of alcoholic liver disease, monocytosis was first reported on 1983, however, the mechanism mediates this clinical feature has been unclear. Recently data has been shown that activated monocytes have been postulated to play an important role in the pathogenesis of alcoholic liver disease (ALD), in which can produce Interleukin-1 (IL-1) induces interleukin-6 (IL-6) production during acute alcoholic liver injury phase reactant. The number of monocytes, one of the most important components of the inflammatory process in ALD maybe as an independent marker that can be utilized to determine the disease severity and predict outcome of the patients.

Conclusion
Our result suggests that monocytosis is associated with acute alcoholic hepatitis (Table 1). Further research may provide us with a better understanding of the clinical scenario and help elucidate the best prevention and treatment options of alcohol–related liver disease.

Disclosures:
No relevant conflicts of interest to declare.
The Relevance Of CD4 Cell Counts and Abnormal Bone Marrow Findings Among HIV-Infected Patients
Authors: Rattanathammethee Thanawat , Norasetthada Lalita , Tantiworawit Adisak , Rattarittamrong Ekarat , Chai-adisaksopha Chatree , Hantrakool Sasinee , Nawarawong Weerasak 
Published: October 2019

Background
Hematologic and bone marrow abnormalities in patients with the HIV infection are common. The incidence of cytopenias correlates directly with the degree of immunosuppression. The causes of these abnormalities include impaired hematopoiesis, immune-mediated cytopenia, nutritional deficiencies, and drug effects.

Objectives
The aim was to study the correlation of CD4 cell counts and bone marrow abnormalities in HIV-infected patients, including the clinical factors predicting bone marrow infection.

Methods
We retrospectively reviewed the records of HIV-infected adult patients who had undergone a bone marrow examination in Chiang Mai University Hospital between 2006 and 2010. The clinical characteristics, laboratory results and bone marrow findings were recorded.

Results
There were 185 HIV-infected patients with a median age of 41 years (range 24-75). At the time of bone marrow examination, 84.3% of patients had fever and/or cytopenia in which 48% of them had bicytopenia/pancytopenia. Abnormal bone marrow findings were found in 77 (41.6%) patients, including dysplastic changes (22.1%), bone marrow infection (12.4%) and lymphoma involving bone marrow (2.7%). The bone marrow infection were independently associated with CD4 counts of less than 50/microlitre [OR 5.5 (95%CI: 1.21-25.46), p-value = 0.02], hepatosplenomegaly [OR 4.16 (95%CI: 1.40-12.34), p-value = 0.010] and fever > 38.5°C [OR 3.90 (95%CI: 1.06-14.28), p-value = 0.040]. Among patients with disseminated fungal infection, blood and bone marrow cultures were positive in 67.6% and 67.6%, respectively while only 37.8% of patients, fungi can be demonstrated microscopically in Wright-stained bone marrow smears. For patients with disseminated mycobacterial infection, blood and bone marrow cultures were positive in 44.4% and 77.8%, respectively while only one-third of patients, acid-fast bacilli can be detected microscopically in bone marrow smears.

Conclusions
Indices of suspected bone marrow infection among patients with HIV infection were lower CD4 cell counts of less than 50/microlitre, hepatosplenomegaly and high-grade fever. Blood and bone marrow cultures were more sensitive than microscopic examination of bone marrow in detection of disseminated fungal or mycobacterial infection. For feverish HIV patients, the specific antimicrobial therapy can be initiated promptly after microscopic detection of microorganism in the bone marrow smear.

Disclosures:
No relevant conflicts of interest to declare.
Quantitative Defects Of Cellular Immune Responses In Patients With Newly-Diagnosed Diffuse Large B-Cell Lymphoma
Authors: Rujirojindakul Pairaya 
Published: October 2019

Altered immune status in non-Hodgkin lymphoma is characterized by undesired autoimmune phenomena and frequent occurrence of infections. The immune defects may be responsible for the initiation, maintenance and progression of malignant clone. We therefore evaluated immune effector cells between 35 patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL) and 34 age- and sex- matched healthy controls using three-color flow cytometry. For patients with DLBCL, there were 19 males and 16 females with a mean age of 59.9 ± 15.6 years. There were 6, 17 and 13 patients with ECOG > 2, stage III-IV and high intermediate to high International Prognostic Index, respectively. We found significant decreases in CD3+CD4+, CD4/CD8 ratio, CD4 central memory (CD4+CD45RO++CD27+) and B cells (Figure 1). From conditional logistic regression, only CD4/CD8 ratio showed significant association with being cases with the odds ratio of 0.29 (95% CI 0.12, 0.68).

Disclosures:
No relevant conflicts of interest to declare.
Fungus Bloodstream Infection In Patients With Haematological Malignanciest
Authors: Feng Ru , Jing Hui , Wei Yongqiang , Huang Fen , Zhang Yu , Li Xiaofang , Wei Qi , Dai Min 
Published: October 2019

Objective
To investigate clinical characteristics, fungal species, predisposing and prognostic factors of hematological patients with fungemia. Method: The clinical data of clinical features, distribution of fungus, risk factors of 47 hematological patients with fungemia in our department were retrospectively analyzed. Results: All patients suffered from fever and received broad-spectrum antibiotic treatment. Agranulocytosis occurred in 42(89.4%) patients. Thirty-two (68.1%) patients were nosocomial infections. Forty-three (91.5%) patients were complicated by infections of other sites, the most common site of infections was from respiratory(78.6%). 29 (61.7%) patients with more than 15 hospitalized days before fungemia. Candida tropicalis (57.1%)was the most frequently fungal isolate. Among Of the 47 patients, 12 (25.5%) patients were dead. By multivariate logistic regression analysis, the duration of agranulocytosis, presence of shock, and the initiation of antifungal therapy are the independent prognostic factors for mortality. Conclusion: To pay attention to antifungal prophylaxis for hematological patients with the predisposing factors of fungemia. To treat fungemia promptly and appropriately, shorten duration of agranulocytosis and prevent shock to improve the prognosis.

Disclosures:
No relevant conflicts of interest to declare.