bluuebunny/crossref_metadata_2025_split huggingface dataset:
Herpesvirus Infections of Intestinal Tract in the Patients with Intestinal Graft-Versus-Host Diseases: Laboratory Diagnosis Based on DNA Detection By Real-Time Quantitative PCR in Feces Samples
Authors: Lin Ren , Liu Wenjun , Huang Fen , Luo Tingyue , Mo Wenjian , Gu Yingying , Xu Na , Chang Yuan , Fan Zhiping , Liang Xinquan , Wu Yuanbin , Wang Shunqing , Du Jing , Hui Liu , Wang Caixia , Sun Jing , Liu Qifa 
Published: November 2021

Abstract
Background: Intestinal herpesvirus disease remains one of the major causes of morbidity and mortality after allogeneic hematopoietic stem cell transplantation (allo-HSCT). There is lack of useful methods for etiological diagnosis of intestinal herpesvirus diseases. Here, we evaluated the efficiency of detecting herpesvirus in feces samples via real-time quantitative PCR (RQ-PCR) for diagnosis of intestinal herpesvirus diseases after allo-HSCT.
Methods: This was a multicenter, prospective study. Patients with refractory diarrhea after intestinal graft-versus-host diseases (GVHD) were enrolled in this study. Laboratory tests which consisted of morphologic examination, immunohistochemistry, in situ hybridization, and RQ-PCR of tissue homogenate were used to detect viral pathogens including cytomegalovirus (CMV), epstein-Barr virus (EBV), herpes simplex virus (HSV)-I, HSV-II, varicella zoster virus (VZV), adenovirus (ADV) and human herpes virus (HHV)-6, HHV-7. These viruses aforementioned were also detected in feces and blood samples.
Results: One hundred and seven patients with refractory diarrhea after intestinal GVHD were enrolled between January 2016 and December 2020. Based on the detection of viruses in biopsy specimens, 75 patients were diagnosed as intestinal infectious diseases including 64 accompanying with intestinal GVHD. CMV was the most frequent pathogen of intestinal infectious diseases (53.8%), followed by EBV (36.5%), bacteria (3.4%) and others (6.3%). For diagnosis of intestinal CMV diseases, the sensitivity and specificity of RQ-PCR in feces samples were better than those of blood (sensitivity: 96.9% v.s. 72.5%, p=0.004; specificity: 93.6% v.s. 75.8%, p=0.035). Similarly, the sensitivity of RQ-PCR in feces and blood samples were 88.2% and 21.9% (p&lt;0.001) and the specificity were 98.5% and 86.3% (p=0.032) for diagnosis of intestinal EBV diseases.
Conclusion: Intestinal infectious diseases were one of the main causes of refractory diarrhea after intestinal GVHD. Herpesviruses, especially CMV and EBV, were the most common pathogens. Herpesvirus-DNA detection by RQ-PCR in feces samples was a useful diagnostic method for intestinal herpesviruses diseases.

Disclosures
No relevant conflicts of interest to declare.
Venetoclax 400mg Combined with Bortezomib and Dexamethasone Is Efficacious and Feasible for Plasma Cell Dyscrasia
Authors: Lu Jin 
Published: November 2021

Abstract
【Abstract】 Objective: To investigate the efficacy and safety of BCL-2 inhibitor Venetoclax (Ven) 400mg combined with bortezomib and dexamethasone in plasma cell dyscrasia with t(11,14). Methods: The data of twenty patients with plasma cell dyscrasia with t (11;14) were retrospectively analyzed.The majority of patients received Venetoclax 400mg combined with bortezomib and dexamethasone. The baseline clinical information, treatment efficacy and adverse effects after Ven-based regimen. Results: Seventeen multiple myeloma patients, two light-chain amyloidosis and one primary plasma cell leukemia (pPCL) patients were studied. Among seventeen MM patients, the median follow-up was 9.0 (0.5-27) months and the median treatment cycles was 4 (1-12);fourteen patients have been evaluated for response rate. The overall response rate for evaluable patients (ORR) was 85.7%, among that one patient (7.1%) achieved CR, four patients (28.6%) achieved VGPR and 7 (50%) achieved PR. The median progression-free survival (PFS) was11.0 months (95%CI 2.1-19.9); the median Overall survival (OS) was 14.0 months (95%CI 6.9-21.1). Two amyloidosis patients achieved VGPR and PR respectively, while one pPCL patient achieved CR. The most common grade 3 or worse treatment-emergent adverse events were thrombocytopenia (15%), infection (10%), neutropenia (5%), diarrhea (5%) and peripheral neuropathy (5%). There was no treatment-related death. Conclusion Ven (400mg) combined with bortezomib and dexamethasone is feasible, tolerated and efficacious in plasma cell dyscrasia.
【Key words】Plasma cell dyscrasia; Venetoclax; Efficacy; Safety

Disclosures
No relevant conflicts of interest to declare.
Post-Transplant Blockade of CXCR4 Improves Complete Remission Rates and Donor Stem Cell Engraftment without Aggravating Gvhd
Authors: Su Long , Fang Ming Hui , Zou Jun , Gao Su Jun , Gu Xiao Yi , Meng Xian Di , Wang Xue , Hu Zheng , Yang Yong Guang 
Published: November 2021

Abstract
Allogeneic hematopoietic cell transplantation (allo-HCT) is a promising therapeutic option for hematological malignancies, but relapse resulted predominantly from residual disease in bone marrow (BM) remains the major cause of treatment failure. Using immunodeficient mice grafted with laboratory-generated human B-ALL, our previous study suggested that leukemia cells within the BM were resistant to graft-versus-leukemia (GVL) effects, and mobilization with CXCR4 antagonist may dislodge leukemia cells from BM, rendering them destroyed by GVL effects. In this study, we extended this approach to patient-derived xenograft (PDX) and murine T-ALL and AML models for determining its clinical relevance and effects on GVHD and donor hematopoietic engraftment. We found that post-transplant treatment with CXCR4 antagonist AMD3100 significantly improved eradication of leukemia cells in the BM in PDX mice grafted with B-ALL cells from multiple patients. AMD3100 also significantly improved disease-free remission rates in murine T-ALL and AML models, and promoted donor hematopoietic engraftment in mice following non-myeloablative allo-HCT. Furthermore, post-transplant treatment with AMD3100 had no detectable deleterious effect on acute or chronic GVHD. These findings provide important preclinical data supporting the initiation of clinical trials exploring combination therapy with CXCR4 antagonist and allo-HCT.

Disclosures
No relevant conflicts of interest to declare.
Prophylactic Treatment of Severe Haemophilia Á Patients with Inhibitors to FVIII with Peglip-FVIII
Authors: Timofeeva Margarita , Zozulya Nadezhda I. , Pospelova Tatiana , Kosinova Marina V , Kurtov Igor , Tuddenham Edward , Ling Gavin 
Published: November 2021

Abstract
Background: FVIII replacement therapy is ineffective for severe haemophilia A (HA) patients who develop inhibitors to FVIII. Patients with intractable inhibitors currently require FVIII mimetics and/or bypassing agents to prevent bleeding. PEGylated liposomes (PEGLip) have been shown to protect FVIII from anti-FVIII antibodies in ex-vivo human studies and in combination with FVIII may present an option for the prophylactic treatment of inhibitor patients.
Aims: To (a) demonstrate that PEGLip-FVIII administered intravenously (IV) to severe HA patients with history of inhibitors to FVIII enhances their clotting activity, (b) compare the number of bleeding episodes before and after PEG-Lip treatment, and (c) demonstrate that PEGLip-FVIII is well tolerated with no increase in inhibitor titres.
Methods: Stage A: Four patients with a history of inhibitors were given single IV injections of PEGLip-FVIII (simoctocog alfa) at a dose of 22mg/kg PEGLip + 35 IU/kg FVIII and assessed for clotting activity at 0 hours (pre-injection) and at 20min, 1, 2, 4, 8, 24 hours, and daily thereafter up to 7 days using Rotational Thromboelastometry. Stage B: Patients received IV injections of PEGLip-FVIII for 6-weeks at a frequency determined by the investigator based on results obtained during Stage A. Inhibitor titres were monitored throughout.
Results: Results are shown below.
Treatment with PEGLip-FVIII was highly tolerated with no clinically significant changes in inhibitor titres. No Adverse Drug Reactions were reported. The mean frequency of administration of PEGLip-FVIII was every 5.7±1.4 days. The mean number of bleeding episodes reported during Stage B was 0.5±0.9 per month (due to 1 patient) compared with 0.9±0.4 per month recorded during the 24 weeks prior to enrollment.
Conclusion: PEGLip-FVIII in inhibitor patients demonstrated efficacy in preventing spontaneous bleeds without increasing inhibitor titres, indicating a novel FVIII-based treatment for this cohort. Planned studies in a larger cohort may confirm our findings.
Figure 1 Figure 1.

Disclosures
No relevant conflicts of interest to declare.
Liposome-Encapsulated Cytarabine and Daunorubicin (CPX-351) Induces Remission in Newly Diagnosed Pediatric Secondary Myeloid Malignancies
Authors: Caldwell Kenneth J , Hu Yixin , Onciu Mihaela , Federico Sara M , Salek Marta , Lewis Sara , Lei Shaohua , Zhang Jinghui , Nichols Kim E. , Takemoto Clifford M , Triplett Brandon M , Farrar Jason E , Rubnitz Jeffrey E. , Ribeiro Raul C , Wlodarski Marcin W. 
Published: November 2021

Abstract
Secondary myelodysplastic syndromes and acute myeloid leukemia (sMDS/AML) are rare myeloid neoplasms in children/adolescents and have a dismal prognosis. The mainstay therapy is hematopoietic cell transplantation (HCT) but there has been little therapeutic innovation for decades and outcomes remain poor. CPX-351, a fixed 5:1 molar ratio of liposomal cytarabine/daunorubicin, has shown favorable safety and efficacy in elderly individuals with sAML and children with relapsed de novo AML, which led the FDA to recently expand the label of CPX-351 to include pediatric patients with secondary AML, however, no data has been reported in this patient group. We report the outcomes of seven young patients with newly diagnosed sMDS/AML uniformly treated with CPX-351. Five patients had previously received chemotherapy for osteosarcoma, Ewing sarcoma, neuroblastoma, or T-ALL; one had predisposing genomic instability disorder (Cornelia de Lange syndrome); and one presented with MDS-related AML and multi-organ failure. The median age at diagnosis of myeloid malignancy was 17 (13-23) years. We identified somatic mutations and copy-number changes across 16 leukemia driver genes in six cases (including TP53 in two), abnormal karyotypes in six cases and rearrangements involving MECOM or NIM1K-TERT in two patients. Additional genomic studies identified pathogenic germline mutations in CHEK2 and SMC3 each in a single patient . Patients received 1-3 cycles of CPX-351 (100 units/m 2 on days 1, 3, and 5) resulting in complete morphologic remission without overt toxicity or treatment-related mortality. This approach allowed for adding FLT3 inhibitor as individualized therapy in one patient. Six patients were alive and leukemia-free at 0.51-3.25 years after HCT. One patient died from disease progression before HCT. Concluding, CPX-351 is an effective and well-tolerated regimen for cytoreduction in pediatric secondary myeloid malignancies warranting further investigation
Figure 1 Figure 1.

Disclosures
Triplett: Miltenyi: Other: Travel, meeting registration.
A Clinical Study of 15 Acute Leukemia Patients with Plasmacytoid Dendritic Cells Expansion
Authors: Zhou Ya-Lan , Wei Yan , Liu Xiaohong , Wang Jing , Jia Jinsong , Shi Hong-Xia , Chang Ying-Jun , Zhao Xiao-Su , Liu Yan-Rong , Ruan Guo-Rui , Huang Xiao-Jun , Jiang Hao 
Published: November 2021

Abstract
Objective: To improve the understanding of acute leukemia with plasmacytoid dendritic cells (pDCs) expansion. Method: Bone marrow smears and flow cytometry immunophenotyping results of patients with acute leukemia and pDCs expansion at diagnosis in our clinical center from August 2018 to January 2021 were retrospectively analyzed. The clinical and biological characteristics were analyzed. Results: Among the 1039 patients with acute leukemia, 15 (1.4%) had pDCs expansion at diagnosis, with a median age of 55 (28-99) years old. The ratio of men to women was 3 to 2. The median proportion of pDCs accounting for all the nucleated cells in bone marrow smear and flow cytometry immunophenotyping were 12.0% (6.0%-50.0%) and 16.6% (4%-28%), respectively. There were 12 cases of acute myeloid leukemia (AML), 11 of them had mutations in RUNX1 and 10 were morphologically classified as AML-M4 or M5. Notably, CD56 was mostly negative (only 1 of the 15 patients expressed CD56 antigen partially) and one of these 15 patients had definite skin lesions, which were significantly different from Blastic plasmacytoid dendritic cell neoplasms. 3 cases were diagnosed as acute lymphoblastic leukemia (ALL), of which 2 cases had mutations in NOTCH1 and RAS signaling pathways. 9 out of the 15 cases had consecutive prognostic information and the median follow-up time was 14.9 (2.1-31.9) months, of which 6 received allogeneic hematopoietic stem cell transplantation(allo-HSCT) and all were in continuous remission. However, among the 3 non-transplanted patients 2 cases relapsed. Conclusion: Acute leukemia with pDCs expansion is a group of patients with characteristic mutation profiles and relatively poor prognosis, more common in AML with abnormal expansion of the mononuclear system. Allo-HSCT may improve the clinical outcomes of these patients.
Figure 1 Figure 1.

Disclosures
No relevant conflicts of interest to declare.
CARD19, a Novel Negative Regulator of B-Cell Tolerance
Authors: Zheng Yongwei , Yu Mei , Chen Yuhong , Xue Liquan , Zhu Wen , Fu Guoping , Burns Robert , Morris Stephan , Wen Renren , Wang Demin 
Published: November 2021

Abstract
The CARD11-Bcl10-Malt1 (CBM) signalosome controls TAK1 activation to regulate B-cell receptor (BCR)-induced NF-κB activation and B cell biology. The biological function of caspase recruitment domain family member 19 (CARD19), originally identified as a BCL10-interacting CARD protein (BinCARD), is not known. Here we found CARD19 strongly interacted with TAK1 but not BCL10 or other CBM components and prevented TAK1's association with TAB2, thereby inhibiting TAB2-mediated TAK1 ubiquitination and activation and subsequent NF-κB activation. CARD19 was ubiquitously expressed in hematopoietic lineages but its deficiency in mice had no effect on hematopoiesis, including B cell development and humoral immune response. CARD19 deficiency enhanced clonal deletion, receptor editing and anergy of self-reactive B cells, thus reducing autoantibody production in vivo. Mechanistically, CARD19 deficiency led to an increase of BCR/TAK1-mediated NF-κB activation. Activation of NF-κB, such as c-Rel, was responsible for the up-regulation of BCR-induced expression of the transcription factor early growth response genes 2 and 3 (Egr2, Egr3) and the E3 ubiquitin ligases, c-Cbl and Cbl-b, the important inducers of B-cell tolerance in B cells. Further, high-throughput RNA sequencing analysis revealed that CARD19 deficiency did not affect the overall antigen-induced gene expression in naïve B cells but suppressed BCR signaling to increase hyporesponsiveness of self-reactive B cells. Consequently, CARD19 deficiency prevented Bm12-induced experimental systemic lupus erythematosus (SLE) and autoimmunity in a B cell-intrinsic manner. Taken together, CARD19 negatively regulates BCR-induced NF-κB activation via blocking TAK1/TAB2 interaction and its deficiency leads to NF-κB-induced expression of Egr2/3 and c-Cbl/Cbl-b in self-reactive B cells, which enhances B-cell tolerance and thus prevents autoimmunity.

Disclosures
No relevant conflicts of interest to declare.
Clinicopathological Characteristics of Subcutaneous Panniculitis-like T-Cell Lymphoma in Asian Population: A Retrospective Cohort of 48 Patients
Authors: Ponvilawan BEN , Likasitwatanakul Pornlada , Sitthinamsuwan Panitta , Siritanaratkul Noppadol , Khuhapinant Archrob , Chairatchaneeboon Manasmon , Samutpradit Danai , Phikulsod Ployploen 
Published: November 2021

Abstract
Background: Subcutaneous panniculitis-like T-cell lymphoma (SPTCL) is a rare subtype of cutaneous T cell lymphoma. Despite its higher prevalence in Asia than other regions, the clinicopathological data of SPTCL in Asian population is scarce.
Materials and Methods: Patients who were diagnosed with SPTCL in Siriraj Hospital, Thailand, from 2010 to 2021 were identified. Demographic, clinical, and laboratory data were retrospectively collected from the hospital database. All statistics were performed in IBM SPSS Statistics Version 23. All continuous variables were reported as medians and their associated ranges.
Results: A total of 48 patients, comprising of 13 males and 35 females, were included in this study. The median age of the cohort was 30 years old. Seven (14.6%) patients had previous or concurrent autoimmune diseases. Seven (14.6%) patients presented with concomitant hemophagocytic lymphohistiocytosis (HLH) at diagnosis. Out of 14 patients who were tested for T-cell receptor (TCR) gene rearrangement, 9 were positive for at least one of monoclonal TCR-β, -γ, or -δ gene rearrangement. The summary of characteristics, presentations, and laboratory results of patients were shown in Table 1. 34 and 14 patients received immunosuppressant therapy (IMT) and chemotherapy (CMT) as their first line of treatment, respectively. The response rates were comparable in both groups.
Conclusions: Clinical presentations of SPTCL in patient's cohort in Asian population are similar to those reported in Western population except a higher rate of autoimmune features. IMT and CMT resulted in similar short-term outcome. Further studies on long-term outcome and the predictive markers for treatment response will be beneficial for this rare subtype of T-cell lymphoma.
Figure 1 Figure 1.

Disclosures
Khuhapinant: Astellas Pharma, Inc.: Research Funding.
An Accurate Prognostic Index Model for Adult HLH (HHLWG-HPI): A Multicenter Retrospective Analysis in China
Authors: Shen Ziyuan , Jin Yingliang , Sun Qian , Xu Linyan , Qiao Jianlin , Huang Shuiping , Xu Kailin , Sang Wei 
Published: November 2021

Abstract
Hemophagocytic lymphohistiocytosis (HLH) is an immune disorder with rapid progression and poor survival. Individual treatment strategy is restricted, due to the absence of precise stratification criteria. In this multicenter retrospective study, we aimed to develop a feasible prognostic model for adult HLH in China. A total of 270 newly diagnosed patients of adult HLH were retrieved from Huaihai Lymphoma Working Group (HHLWG), of whom 184 from 5 medical centers served as derivation cohort, and 86 cases from 3 other centers served as validation cohort. X-Tile program and Maxstat analysis were used to identify optimal cut-off points of continuous variables; univariate and multivariate Cox analysis were used for variables selection, and Kaplan-Meier curve was used to analyze the value of variables on prognosis. The C-index, brier score and calibration curve were used for model validation. Multivariate analysis showed that age, creatinine, albumin, platelet, lymphocyte ratio and alanine aminotransferase were independent prognostic factors. By rounding up the hazard ratios from 6 significant variables, a maximum of 9 points was assigned. The final scoring model of HHLWG-HPI was identified with four risk groups: low risk (≤3 pts), low-intermediate risk (4 pts), high-intermediate risk (5-6 pts), and high risk (≥7 pts), with 5-year overall survival rates of 68.5%, 35.2%, 21.3%, and 10.8%, respectively. The C-indexes were 0.796 and 0.758 in derivation and validation cohort by using bootstrap resampling program. In conclusion, the HHLWG-HPI model provides a feasible and accurate stratification system for individualized treatment strategy in adult HLH.

Disclosures
No relevant conflicts of interest to declare.
Epidemiology and Risk Factors for Infections in Myelodysplastic Syndromes
Authors: Poloni Antonella , Carturan Alberto , Pianelli Michelangelo , Morsia Erika , Lame Dorela , Olivieri Attilio 
Published: November 2021

Abstract
Background: Patients with MDS are at high risk of developing infections, which still represent the most frequent complications and the main cause of mortality and morbidity. We conducted a retrospective study with the aim of evaluating incidence, characteristics and outcome of infectious events in patients with myelodysplastic syndromes (MDS) and the risk factors associated with them.
Patients and methods: 200 patients with MDS or LMMC followed by the Ancona Hematology Clinic in the last 15 years were included. In this group, we evaluated severe infectious episodes and associated risk factors, relating to patient, disease and therapy.
Results: In a cohort of 200 patients, we detected 65 cases of infections of higher than third grade according to WHO. Pneumonia is the most frequent infection, especially on a bacterial basis. Risk factors that have shown significant association with infections ≥ G3 are: comorbidity (p = 0.0086), hemoglobin level (P = 0.0111), neutropenia (P = 0.0152), transfusion dependence during the course of disease (P &lt;0.0001) and hypomethylating therapy (P = 0.0014). A subanalysis confirmed comorbidities as risk factors for the development of pneumonia (P = 0.0322) and azacitidine therapy as a risk factor for sepsis (P = 0.0038). The overall survival of the cohort is approximately 7.5 months and the predictive factors of survival are patient age (P = 0.0005), WHO disease class (P = 0.001), R-IPSS (P &lt;0.0001) and transfusion-dependence during the course of the disease (P &lt;0.0001). Multivariate analysis confirmed age (P = 0.0002), R-IPSS (P = 0.0043) and transfusion-dependence (P = 0.0006) as predictors of survival. Infections above grade 3 do not impact survival. Otherwise, there was a trend of reduced survival in patients who had pneumonia (P = 0.0612) or sepsis (P = 0.0927).
Conclusion: Patients with MDS have a high probability of encountering an infectious problem in the course of the natural history of the disease. In one out of five cases, there are more than one infectious event. Particularly at risk of infection are patients with comorbidities, neutropenia (PMN &lt;800 / mm³), significant transfusion needs and on therapy with hypomethylating agents. These patients should be carefully monitored for infectious complications.

Disclosures
No relevant conflicts of interest to declare.