bluuebunny/crossref_metadata_2025_split huggingface dataset:
Role of Serial Positron Emission Tomography (PET) Scans in Indolent Lymphomas' Management - Interim Results from an Ongoing Prospective Study at King Fahd Medical City, Riyadh, Saudi Arabia
Authors: Alshehry Nawal Faiez , Ahmed Musab , Iq bal Shahid , Gill Atta Munawar , Dawiama Mohammad E , Butt Ahmed Ali , Albtoosh Belal , Motabi Ibraheem H. , AlGhamdi Mubarak S. , Tailor Imran Khan , Altaf Syed , Zaidi Syed Ziauddin A. , Raja Shanker 
Published: October 2019

Abstract
Background:
Indolent lymphomas (ind-LYM) are a subset of B-cell lymphomas, characterized by slow growth, protracted course without treatment and a tendency to reoccur after therapy. The management of ind-LYM is varied and evolving. To-date reliable tools for imaging based prognostication and treatment strategies are limited. We explored the utility of serial FDG PET scans (baseline (BL), interim/6 months (INT) end of therapy/1 year (EOT)), in managing ind-LYM).
Methods:
From an ongoing prospective study, examining the role of PET scan in ind-LYM at our institution, we performed an interim analysis of all patients hitherto enrolled in our study. Patients diagnosed as ind-LYM and having undergone serial PET scans from 2015 to date (N=40, males= 27, females =13) had median age of 59.68 ± 14.5 (28-82 at diagnosis. All PET scans were obtained per accepted protocols. SUVmax and Deauville scores (DS) were obtained from five target lesions. The average of composite SUV (cSUV) and composite Deauville scores (cDS) were computed for each patient. Statistical analyses (using t-test, mean delta change) were performed with the cSUV and cDS.
Results:
The types of ind-LYM were CLL/SLL (17), Follicular (15), mantle cell (3), marginal zone lymphoma (3), and 1 each of MALT and lymphoplasmacytic lymphoma. The data were analyzed for two arms of the study treatment chemotherapy arm (CHEMO-22/40) and Rituximab + observation arm (OBSR-18/40). At BL, patients on CHEMO had significantly higher cSUV and cDS compared to those who were on OBSR (SUV: 6.99 vs. 4.32 p-value 0.0124; cDS: 4.37 vs 3.71 p-value 0.0075 respectively). Although there was a delta change in the cSUV and cDS in both arms after INT and EOT, both treatment lines showed no significant difference in the SUV mean and DS (p-value: 0.754 and 0.5721, receptively). A 2-tailed T-test was used for delta change of cSUV. BL to INT cSUV was statistically significant (p-valve 0.05) and difference in cSUV was not significant for BL to EOT (p-valve 0.98). Difference in cDS was not significant between BL, INT and EOT.
Conclusion:
The higher cSUV/cDS at BL for the treatment arm may be due to disease profile at the time of presentation and/or selection bias. At EOT no difference in both estimates were noted. Both arms showed similar trends in delta change from BL-INT-EOT. Our findings suggest that SUV and DS at BL maybe an independent criterion for treatment selection in ind-LYM.

Disclosures
No relevant conflicts of interest to declare.
Multi-Dimensional Humanistic Care for the Kids with Hematological Malignancies in Guangzhou Women and Children's Medical Center (GWCMC)
Authors: Huang Haiying , Liang Zhimin , Huang Yongxian , Zhang Hui 
Published: October 2019

Abstract

Objective: To evaluate the effects of multi-dimensional humanistic care on kids with hematological malignancies and their parents and facilitate the effective nursing experience and professional nursing in such clinical care.
Methods: A total of 567 children with cancer and their parents were enrolled in this study. From January to December in 2017, multi-dimensional humanistic care was systematically implemented to provide care for all these patients and their family members. A warm and comfortable in-patient atmosphere was created with regular playing-games, health education meetings, and personal palliative care support were provided to all newly-diagnosed pediatric cancer patients and their parents who admitted to our department. In the meanwhile, case management were implemented by nurses. Children and parents in demand were referred to game therapists and social workers for visits, psychological counseling and emotional support. Financial assistance was also provided to care for those well-off families to support their systemic cancer treatment. Follow-up visits to hospitals were also offered.
Results: The implementation of multi-dimensional humanistic care measures significantly reduced the anxiety level of hospitalized children with cancer and their parents, which in turn improve their treatment compliance. Next, more easier caregiving ability and compliance were also recorded. The results of satisfaction survey showed that the satisfaction to nursing care rose from 85.6% in 2016 to 96.9% in 2017 after the implementation of multi-dimensional humanistic care in our hospital. The nurses' service attitude, medication guidance, hospitalization guidance, timely bedside services, and nurses' operating technology satisfaction also increased by 10.86%, 12.17%, 8.3%, 12.80%, and 12.15% respectively.
Conclusion: The multi-dimensional humanistic care effectively reduces the anxiety of kids with hematological malignancies and their parents, improves the caregiver's caring ability and compliance, and their satisfaction to nursing care. All these results point out the significance of systemic care services in the childhood cancer therapy, it is noteworthy to pour more attention and capacity to the clinics which may facilitate the cancer treatment.
Figure. Figure.

Disclosures
No relevant conflicts of interest to declare.
Cell Intrinsic and Extrinsic Mechanisms Mediate the Role of c-Myc Haploinsufficiency in Controlling HSC Fate
Authors: Sheng Yue , Yu Chunjie , Ma Rui , Qian Zhijian 
Published: October 2019

Abstract
It has been shown that loss of c-Myc leads to accumulation of hematopoietic stem cells (HSCs) and severe cytopenia as a consequence of a blockage of HSC differentiation. Here we report a role of c-Myc haploinsufficiency in regulating HSC quiescence and self-renewal. We showed that c-Myc haploinsufficient mice displayed decreased white blood count and number of lymphocytes with normal myeloid cell differentiation. The number of HSCs and hematopoietic progenitor cells (HPCs) were all decreased significantly in c-Myc haploinsufficient mice as compared with control mice. We found that c-Myc haploinsufficiency inhibited HSC self-renewal capacity, increased proliferation and decreased quiescence of HSCs in vivo. By transplantation assays, we showed that c-Myc haploinsufficiency has extrinsic and intrinsic effects on the maintenance of HSCs in vivo. Our study suggests that loss of c-Myc activity and reduced dosage of c-Myc have distinct effects on HSC functions.
c-Myc is a critical downstream mediator of the Wnt/b-catenin pathway. We showed that c-Myc haploinsufficiency is sufficient to prevent severe anemia in Apc heterozygous mice, and to significantly prolong the survival of Apc heterozygous mice. In addition, treatment of Apc haploinsufficient mice by a c-Myc inhibitor significantly reversed anemia in Apc-deficient mice.
By transplantation assay, we further demonstrated that reduced expression of c-Myc in the bone marrow niche is responsible for prevention of severe anemia in Apc-deficient mice. However, we found that reduction of c-Myc by loss of a single allele of c-Myc did not rescue defective self-renewal capacity of Apc haploinsufficient HSCs. Taken together, our studies indicate that c-Myc mediates the function of the Wnt/b-catenin signaling pathway in bone marrow niche but not in HSCs.

Disclosures
No relevant conflicts of interest to declare.
Survey of Compliance to Infection Control Measures and Its Impact on Healthcare of Patients in a Hematopoietic Stem Cell Transplant Unit
Authors: Yarlagadda Naveen , Krishnan Gayatri , Mohan Meera , Johnsrud Andrew , Wolfe Frankie , Kothari Atul 
Published: October 2019

Abstract
Background:
Isolation precautions are used in hospitals to interrupt the chain of transmission of nosocomial pathogens. There are several reports that isolation negatively impacts the care given to patients. Isolation protocol compliance has been reported between 40-70% in several studies.
Methods:
We conducted an anonymized survey of healthcare providers assessing the knowledge, practice and perceived impact of isolation precautions. The survey was conducted in a hematopietic stem cell transplant unit and a medical unit in an academic medical center. Surveys were given to nursing staff and resident physicians working on those units. Results were analyzed using chi-square test.
Results:
A total of 106 responses were received, 60 from nursing staff and 46 from resident doctors. Self- reported compliance to hand hygiene practices was 59.9%, this was significantly higher on leaving as compared to entering patient rooms amongst nurses (72% vs 50%, p=0.015). Overall adherence to isolation precautions was 60.3%, surprisingly nursing staff in the transplant unit had a significantly lower rate as compared to nurses in the medicine unit (44% vs 83%, p=0.025). 70.7% of respondents felt that patients on isolation precautions have to wait longer for non-emergent care. Only 56.6% of respondents felt that patients were educated about the reasons for isolation precautions; this number was significantly lower in residents as compared to nurses (41.3% vs 68.3%, p=0.005). 77.3% felt that patients in isolation are less satisfied in the care they received. 86.9% of resident physicians felt that isolation precautions helped reduce the spread of infection vs 68.5% of nurses (p=0.025). 82% of respondents expressed overall satisfaction with infection control practices.
Conclusions:
In our survey, we observed a low compliance of hand hygiene and isolation practices. While respondents felt that isolation adversely impacted patient satisfaction and care, they also opined that these practices help reduce the spread of infection. Surveys can be an important tool to assess knowledge and impact of infection control practices; and can be used to direct quality improvement initiatives.

Disclosures
No relevant conflicts of interest to declare.
Genomic and Immune Profiles of Multiple Myeloma Revealed By Whole Genome and Transcriptome Sequencing
Authors: Yoon Christopher J. , Song Hyojin , Song Seulki , Park Hyejoo , Shin Dong-Yeop , Hong Junshik , Kim Inho , Lee Hyun Jung , Kim Byung-Su , Lee Jung Lim , Yoon Sung-Soo , Ju Young Seok , Koh Youngil 
Published: October 2019

Abstract
Introduction:
We analyzed genomic profile in line with immune checkpoint molecule expression in multiple myeloma using whole genome sequencing (WGS) and whole transcriptome sequencing (WTS) data.
Methods:
We performed WGS of CD138+ selected tumor and the matched normal from saliva of multiple myeloma patients at 90-60x and 30x respectively from 37 patients. At the same time, we performed WTS using both tumor (CD138+) and immune milieu (CD138-) samples from these patients. Structural variations were called with Delly2 and Manta and the intersect of two call sets were used as the final SV calls. Copy number analysis was done with Sequenza and custom scripts. Somatic single nucleotide variants were identified with Mutect1 and Strelka and filtered against the panel of normal. RNA-seq was aligned using STAR algorithm and gene expression was quantified using RSEM algorithm. We extracted the expression of 21 immune checkpoint-related molecules (LAG3, PD-L1, IDO1, TIM3, CD27, CTLA-4, ICOS, TIGIT, PD-1, PD-L2, VISTA, and their ligands). To compare cell populations within a set of CD138-sorted MM samples, we used CIBERSORT algorithm to estimate predict fractions of leukocyte RNA.
Results & Discussion:
A total of 1,359 somatic structural variants were identified, with a median of 28 structural variant events per patient. The most common translocation event was t(4;14) (n=6, 16.2%). We identified novel recurrent deletions in CCSER1 (n=5, 13.5%) either deleting exon 10 (n=3) or exon 6 (n=2). CCSER1 has been proposed to a have a role in cell division with defects leading to cytokinetic defects. We observed an enrichment of whole-genome duplicated samples with CCSER1 deleted patients. We propose that CCSER1 deletion may have a role in whole-genome duplication events seen in multiple myeloma. Chromothripsis was also seen in 7 patients (18.9%). A total of 9 chromothripsis events were observed and chromosome 6 was most frequently involved (n=3). Recurrent mutation in IGKV4-1 chr2: 89185484 and 89185485 (p.Ala60) was observed suggesting dysfunctional antigen recognition in myeloma cells.
From immune checkpoint perspective, expression of Galectin-9, a ligand of TIM3, was outstandingly high in immune milieu suggesting potential role of TIM3 inhibitor in myeloma. On the other hand, VISTA was highly expressed in tumors. When we matched the transcriptomic profiles with genomic variants, NRAS G61R mutant showed high expression of TIM3/Galectin-9 axis suggesting characteristics immune milieu of RAS mutant myeloma.
Conclusions:
We could identify novel CCSER1 recurrent deletion and IGKV4-1 mutation in multiple myeloma using WGS. WTS immune milieu analysis suggest potential role of TIM3 inhibitor in myeloma, especially in RAS mutated cases.
Figure. Figure.

Disclosures
No relevant conflicts of interest to declare.
Lysine Histone-Induced Thrombocytopenia in Zebrafish Depends on Endothelial Von Willebrand Factor
Authors: Zheng Liang , Zheng X. Long 
Published: October 2019

Abstract
Thrombotic thrombocytopenic purpura (TTP), a potentially fatal blood disorder, is caused by severe deficiency of plasma ADAMTS13 activity, primarily resulting from acquired autoantibodies that inhibit ADAMTS13's ability to cleave von Willebrand factor (VWF). However, severe deficiency of plasma ADAMTS13 activity alone is often not sufficient to cause an acute episode of TTP; additional environmental or genetic factors may be required for the development of acute TTP. Here, we report a creation and characterization of a novel zebrafish model of TTP and use the model to identify a potential mechanistic link between an innate immunity and onset of TTP. Using CRISPR/cas9, we generated adamts13-/-,vwf-/-, and adamts13-/-vwf-/-zebrafish on a double transgenic (Fli1-eGFP/Gata1-dsRed) background in which erythrocytes, thrombocytes, and endothelial cells were uniquely labeled with an endogenously expressed fluorescent protein. Our results demonstrated that adamts13-/-zebrafish larvae (5-dpf) had an increased rate of developing occlusive thrombi in the caudal venues after FeCl3 injury; also, adamts13-/- adult zebrafish (3-4 months) exhibited ~27% reduction of their total or mature thrombocyte counts with a significantly increased number of fragmented erythrocytes; moreover, an intraperitoneal administration of a lysine-rich histone resulted in severe and more persistent thrombocytopenia with an increased mortality in adamts13-/-zebrafish than their wild-type littermate; finally, both spontaneous and histone-induced thrombocytopenia and thrombotic microangiopathy in adamts13-/-was eliminated when endothelial vwf was genetically deleted from zebrafish. Together, these results provide experimental evidences to support a mechanistic link of acute infection or inflammation to acute onset of TTP in patients lacking plasma ADAMTS13 activity.

Disclosures
Zheng: Alexion: Research Funding, Speakers Bureau.
Clinical Significance of Germ Line and Acquired Somatic Mutations of 30 High Frequency Genes in Hematologic Malignancies
Authors: Zhang Nanchen , Gong Yuping 
Published: October 2019

Abstract
Objective: To analyse germ line and acquired somatic mutations of 30 high frequency genes and explore their clinical significance in hematologic malignancies. Methods: A total of 254 patients with hematologic diseases (145 males and 109 females) from Jan 2017 to Apr 2018 in the Southwest China were included and the samples from bone marrow and oral mucosa were collected, and the gene mutations of germ line and acquired somatic cells were examined by the next-generation sequencing technology or PCR. The frequency and locus of germ line and acquired somatic mutations of 30 high frequency genes, as well as their clinical significance to the diagnosis and classification in hematologic diseases were analysed. Results: 1.The frequency and locus of germ line and acquired somatic mutations, and their clinical significance: no mutation was detected in 24 cases (9.4%), and a total of 659 genetic locus mutations were detected in 230 cases (90.6%), including 520 somatic cell mutations (78.9%) and 139 germ line mutations (21.1%). The results of gene mutations are listed in order: the number of acquired somatic mutation: the number of germ line mutation: common mutation locus: the type of hematological disease for the patients diagnosed in the West China hospital, as described in Table 1. 2.Characteristics of acquired somatic and germ line mutations: the genes of WT1, U2AF1, TP53, TET2, STAG2, RUNX1, PIGA, NRAS, KIT, IDH2, EZH2, DNMT3A, CBL and BCOR were dominated by acquired somatic mutations, while the genes of ZRSR2, JAK2 and BCORL1 were dominated by germ line mutations, the genes of SRSF2, SF3B1, SETBP1, PTPN11, NPM1, PHF6, KRAS, IDH1, FLT3-ITD, ETV6 and CEBPA were detected only in acquired somatic mutations, BCOR and ASXL1 have a similar proportion of acquired somatic and germ line mutation; only 42-4C>A of ZRSR2 mutation was existed in both somatic and germ line, however, the mutation sites of the acquired somatic and germ line of other genes have not been found to be existed at the same time. 3.The clinical significance of the acquired somatic and germ line mutation: It was found that the genes of TP53, SF3B1, EZH2 and DNMT3A tend to appear in MDS, the genes of ZRSR2, WT1, U2AF1, TET2, RUNX1, NRAS, NPM1, KRAS, KIT, IDH1/2, FLT3-ITD, CEBPA and BCOR tend to appear in AML, and the similar probability of the STAG2, PTPN11, PHF6, ETV6, CBL, BCORL1, ASXL1 and NF1 genes appear in AML and MDS, while the genes of PIGA tend to appear in PNH, and BCOR in AA. Conclusion: The acquired somatic and germ line mutations are significantly different in the frequency, mutation site and the type of hematological disease, and the further research will clarify their potential roles in the pathogenesis of hematological tumors, and have important clinical significance for the classification and prognosis of the hematological diseases.
Key words: gene mutation, somatic, germ line, hematologic malignancies
Table 1. Table 1.

Disclosures
No relevant conflicts of interest to declare.
Donor KIR3DL1/Receptor HLA-Bw4-80I Combination Reduce Acute Leukemia Relapse after Umbilical Cord Blood Transplantation without in Vitro T-Cell Depletion
Authors: Fang Xinchen , Sun Zimin , Liu Huilan , Xia Lijun 
Published: October 2019

Abstract
Objective: How to reduce relapse is still a puzzle in the treatment of acute leukemia patients with allogeneic umbilical cord blood hematopoietic cell transplantation (UCBT). Donor natural killer (NK) cell alloreactivity in UCBT can control leukemic relapse, However, NK cell function is calibrated through education, that is governed by human leukocyte antigens (HLAs), our study aim to investigate the Graft-resistant leukemia effect after transplantation of KIR3DL1 and its different ligand HLA-B subtypes(BW6, Bw4-80T, Bw4-80I).
Design and method: we retrospectivly analysed single center of 232 acute leukemia patients who underwent UCBT(myeloablative conditioning without ATG). The killer immunoglobulin-like receptor (KIR) genotype of cord blood donors was detected by SSP method, they all contains KIR3DL1. There were 104 cases of acute lymphoblastic leukemia, 112 cases of acute myeloid leukemia, 16 cases of myelodysplastic syndrome. 168 cases of transplant patients in remission period, and 64 cases of non-remission. There were 122 males and 110 females with a median age of 13 years (2-45 years). The patients were divided into three groups according to HLA-B locus, 1.patients had BW6 in both two HLA-B locus(group 1, N=86) , which means uneducated; 2.patients had HLA-Bw4-80T in the HLA-B locus(group 2, N=68), which means educated; 3.patients had HLA- Bw4-80I in the HLA-B locus(group 3, N=77), which means highly educated. The receptors were followed-up from July 31, 2012 to December 30,2017, in graft failure, neutrophil engraftment, platelet engraftment, acute graft-versus-host disease (aGVHD), chronic graft-versus-host disease (cGVHD), relapse, overall survival (OS), and leukemia free survival (LFS).
Results: In group 3 patients, donor KIR3DL1 and receptor HLA-Bw4-80I combinations that were predictive of highly educated were associated with significantly lower relapse (hazard ratio [HR], HR = 0.49; P =0 .004) and better LFS (HR = 0.68, p = 0.014), compared with the educated(group2) and uneducated (group3) group, with no significant increase in aGVHD and cGVHD incidence. While no difference was observed in the other index in the three group.
Conclusion : Alloreactivity of NK cells demonstrated reproducible patterns of strong or weak graft-versus-leukemia (GVL) effect against leukemia blast, which is depend on donor KIR3DL1/receptor HLA-B subtype combinations. Our data suggests that donor KIR3DL1/receptor HLA-Bw4-80I combination in UCBT may achieve superior graft versus leukemia effects, lower risk for relapse among patients with acute leukemia.
Keywords: KIR, Umbilical Cord Blood Transplantation, UCBT, GVL

Disclosures
No relevant conflicts of interest to declare.
Prognostic Value of Epstein-Barr Virus (EBV)-Induced Gene 3 (EBI3) in Diffuse Large B Cell Lymphoma
Authors: Zheng Hong , Huang Juan 
Published: October 2019

Abstract
Background: Epstein-Barr virus (EBV)-induced gene 3 (EBI3) as a subunit for heterodimeric cytokines IL-27 and IL-35, plays important roles both in regulation of T cell proliferation and Th1,Th2 and Th17 cells differentiation. EBI3 was closely related with tumor prognosis. Diffuse large B-cell lymphoma (DLBCL) is the most common lymphoid malignancy in adults with cure-rates of 40-60%. However, Relapse and refractory rate remain in 40% or so. In the present study, we aimed to detect the expression of EBI3 in DLBCL and to analyze its relationship with prognosis.
Methods: We retrospective reviewed medical records of 51 newly diagnosed DLBCL patients in Sichuan People's Hospital between January 2010 and December 2016. Immunohistochemical (IHC) assay was used to detect the expression of EBI3 and PD-1 in DLBCL. The expression of CD5, CD30, Bcl-2, Bcl-6, C-myc and Epstein-Barr virus (EBV)-encoded RNAs (EBERs) in tumor specimens from 53 patients was also detected by IHC. The Kaplan-Meier method with log-rank test was used for univariate analysis. Cox proportional hazards model was used for multivariate analysis.
Results: Of the 51 patients, 40 (78.4%) were EBI3-positive in tumor specimens. And PD-1 expression (39/40) was almost in parallel with EBI3 in tumor specimens. EBI3 expression was common in the non-germinal center B-cell-like (GCB) subtype than in the GCB subtype. Patients with EBI3 expression in tumor were more likely to be resistant to first-line chemotherapy when compared with the patients without EBI3 expression in tumor microenvironment (P <0.05). EBI3 expression in tumor microenvironment was correlated with PD-1 expression (r = − 0.20, P = 0.04). Only one patient with EBI3 expression was no PD-1 expression. No correlations were detected between EBI3 expression and the expression of EBER as well as other markers: ALK, CD5, c-Myc and CD30. The complete remission (CR) rates were 7.5% (3/40) and 71.4% in patients with and without EBI3 expression in tumor cells (P = 0.02). EBI3 expression in tumor cells was an independent risk predictor for ORR (P < 0.05).
Conclusions: Our results indicate that EBI3 associated with poor prognosis and EBI3 may be a potential therapeutic target and prognosis marker.

Disclosures
No relevant conflicts of interest to declare.