bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pre-Surgical Methylene-Blue “targeting” of Small Intrapulmonary Nodules In Patients with Haematological Malignancies: Preliminary Experience.
Authors: Ceesay M. Mansour , Jaffer Ouni , Lung Phillip FC , Marrinan Michael T , Deshpande Ranjit , Mullholland Nicola , Pagliuca Antonio , Mufti Ghulam J. , Desai Sujal R 
Published: October 2019

Abstract
Abstract 4551
The diagnosis of intrapulmonary nodules in patients with haematological malignancies is problematic as such lesions are often small and impalpable and “non-targeted” surgical biopsy is difficult. The aim was to evaluate the utility of image-guided “targeting” of small pulmonary nodules with methylene-blue before video-assisted thoracoscopic (VATS) biopsy. Eleven patients (8M:3F) with median (range) age of 48 (27-62) years with haematological malignancies (lymphoma, n=6, AML/MDS, n=3, ALL, n=1,Castleman's disease, n=1) were referred for VATS biopsy. Equal volume of iodinated contrast) was injected in the vicinity of the target lesion and along a track (including the pleural surface and the overlying chest wall), using a 20G needle. The platelet count, diameter of targeted nodules, “perpendicular” distance from the pleural surface and complications were recorded. Patients were transferred to surgery from the CT suite. The median (range) platelet count was 256×109/L (54-453). The mean (range) diameter of targeted nodules was 12.5(5-22) mm and these were at a mean distance of 14.3±8.3mm from the pleural surface. Complications included small pneumothoracis in 4/11 (36%) patients and pain in 1/11 (9%). A definitive histopathological/microbiological diagnosis was achieved in 10/11 (91%) patients and included: organising pneumonia (n=4), respiratory bronchiolitis (n=2), Kaposi's sarcoma (n=1), mycobacterium fortuitum infection (n=1) and chronic GVHD (n=1). There were no cases of angioinvasive aspergillosis. This preliminary data suggest that pre-biopsy methylene-blue targeting of intrapulmonary lesions is a safe and promising technique for the diagnosis of indeterminate lung nodules in patients with haematological malignancy.

Disclosures:
Mufti: Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau.
Massive Pleural Effusions and Anasarca After Allogeneic Hematopoietic Cell Transplantation.
Authors: Wirk Baldeep 
Published: October 2019

Abstract
Abstract 4556
A 37 year old male with T cell acute lymphoblastic leukemia with normal cytogenetics 46XY in second complete remission (CR2) after 8 cycles of HyperCVAD and 4 cycles of salvage nelarabine underwent myeloablative conditioning with cyclophosphamide TBI for a matched related donor allogeneic stem cell transplant from his brother. His day+100 bone marrow biopsy showed CR2 and was 100% donor. His post transplant course was unremarkable until he relapsed d+162. The immunosuppression was tapered off rapidly and 2 cycles of nelarabine and a donor lymphocyte infusion (1×107 CD3 cells/kg) were completed by d+254 and CR3 was achieved. He did well until d+608 when he presented with a month long history of dyspnea and recurrent bilateral large pleural effusions (despite multiple large volume thoracenteses) and anasarca including facial edema. He had gained 15 kilograms in 2 weeks. He had no fever, skin rash, sicca syndrome or lichen planus. Chest and abdomen CT showed massive bilateral pleural effusions, but no lung infiltrate, pericardial effusion or ascites or lymphadenopathy. The complete blood count, renal function and liver function tests were normal and there was normal hepatopedal flow in the main portal vein and its branches. The echocardiogram showed a left ventricular ejection fraction of 60% (normal) and there were no vegetations. The serum ANA, anti-Ro and anti-La were negative. The bone marrow biopsy showed no evidence of relapse of T cell ALL. The peripheral blood STR was 100% donor. The pleural fluid was transudative and cytology showed no malignancy. Pleural fluid flow cytometry showed no CD20+ B cells but did show polyclonal T cells with a CD4:CD8 ratio of 0.22. The pleural biopsy showed reactive mesothelial cells with mixed acute and chronic inflammation and no malignancy. Ebstein Barr virus in-situ hybridization and HHV-8 immunohistochemistry was negative on the pleural biopsy. All bacterial, fungal and viral (including CMV, EBV, HSV, adenovirus, VZV, HIV, BK) of the blood, urine and pleural fluid were unremarkable. A random skin biopsy of the forearm showed scleroderma. Methylprednisolone 2 mg/kg iv daily and therapeutic tacrolimus with extracorporeal photoporesis was begun with resolution of the pleural effusions and anasarca two months later. On d+903 he remains in CR3 and is on tapering courses of prednisone and tacrolimus without recurrence of the pleural effusions or anasarca. Conclusion: Isolated sterile pleural effusions with anasarca should be recognized as a rare feature of late onset chronic graft versus host disease so as to allow prompt initiation of immunosuppression. The patient shared the HLA antigens HLA DR15 and HLA DQW6 which are associated with autoimmune disease such as systemic lupus erythematosus suggesting that patients with this HLA combination may be more prone to this presentation.

Disclosures:
No relevant conflicts of interest to declare.
Irradiation-Based Myeloablative Cord Blood Transplantation for Hematologic Malignancies In Adults.
Authors: Liu Huilan , Wang Xingbing , Geng Liangquan , Ding Kaiyang , Tang Baolin , Tong Juan , Yao Wen , Wang Zuyi , Sun Zimin 
Published: October 2019

Abstract
Abstract 4583
We retrospectively analyzed of the engraftment, Transplant-related complications and survival after unrelated cord blood transplantation (UCBT) using irradiation-based myeloablative conditioning in adult with hematologic malignancies. Between September 2006 and June 2010, 29 consecutive adult patients with hematological malignancies were treated with UCBT, Thirteen of them were advanced-stage disease and 11 of them were high risk or refractory disease. All patients received four fractionated 12 Gy TBI, total dose 12 g/m2 cytarabine and total dose 120 mg/kg cyclophosphamide as myeloablative conditioning. The median age was 21 years; the median weight was 57 kg. Double or multiple UCB grafts were used for 17 patients, while single UCB graft for 12 patients. the median number of nucleated cells was 3.83×107/kg and 5.25×107/kg. All patients were given a combination of cyclosporine A (CsA) and mycophenolate mofetil (MMF) for graft-versus-host disease (GVHD) prophylaxis. All patients obtained engraftment. Median time to neutrophil≥0.5×109/L was 20 days (range 14–37) and platelet engraftment in 25 patients (≥20×109/L) was 35 days (range 25–49). Chimerism was assessed by PCR analysis of short tandem repeat (STR) sequences on whole blood or bone marrow weekly in cases who were fully donor chimeric from 7 days to 21 days after transplantation. 16 cases developed acute GVHD, more than grade II in three cases. Six of twenty-four patients who survived more than 100 days developed limited chronic GVHD.17 cases were alive and in hematologic remission at a median follow-up of 504 days (range 49 ~ 1245). The probability of over survival at 3 years was 58.6%. Five cases relapsed. Nine of twelve cases died of transplant related complications and infection. These results suggest that UCBT after TBI-based myeloablative conditioning could be safely and effectively used for adult patients with hematologic malignancies.

Disclosures:
Sun: the Fund of the Key Medical Project of Anhui Provincial healthy department (2010A005): Research Funding; the Clinical Technology foundation of Anhui Provincial healthy department (2008A011): Research Funding; the Fund of Anhui Provincial “115” Industrial Innovation Program: Research Funding.
Stem Cell Transplantation for Relapsed and Refractory Burkitt Lymphoma.
Authors: Kwon Steven , Steinberg Amir , Bresee Catherine , Franco Mercedes , Lopez Angela M. , Lim Stephen , Lill Michael 
Published: October 2019

Abstract
Abstract 4589

Background:
Burkitt lymphoma is a highly aggressive and rapidly proliferating hematologic malignancy. Various chemotherapy regimens (HyperCVAD, CODOX-M/IVAC, REPOCH) have been shown to improve overall survival rate. However, in instances of relapsed or refractory disease, there is no clear-cut standard of care. Hematopoietic stem cell transplantation (HCT) has shown benefit in these patients. Here, we report our institutional experience using HCT for relapsed/refractory Burkitt lymphoma.

Methods:
Between February 1994 and January 2010, 13 patients (10 males, 3 females) with refractory or relapsed Burkitt lymphoma were retrospectively evaluated. The patients in question were administered a particular conditioning regimen followed by stem cell transplantation (11 autologous, 2 allogeneic). The average age at transplant was 41.8± 3.4 years (range 24 to 67). Stem cell source was from peripheral blood in all transplants including allogeneic (2 HLA-identical sibling transplants). The conditioning regimens for HCT consisted of the following: TBI/Rituximab/Cytoxan/VP16, TBI/Cytoxan/VP16, BEAM, Cranial Spinal boost/TBI/Cytoxan/VP16 or Cranial boost/TBI/Cytoxan.

Results:
On average, patients received transplant 299 ± 36 days after initial diagnosis (range 153 to 582). All patients achieved engraftment. For the 5/13 deceased patients (38%), cause of death was attributed to relapsed/refractory disease (n=2) and treatment related causes (n=3). Using the Kaplan-Meier method, the average survival time after transplant was computed at 27.7 ± 5.3 months and 75% were alive 2-years after transplant. Likely due in part to the small sample size, no covariates (age, gender, conditioning regimen, HIV status, presence of B symptoms, and CNS or bone marrow involvement) were found to be predictive of survival rates.

Conclusion:
Patients with Burkitt lymphoma, known for its rapid growth, can achieve long-term complete remission (CR) with intense, combination chemotherapy. Despite successful long-term remission rates, a substantial portion of patients die from uncontrolled disease. At the first sign of refractory or relapsed disease, resources should be mobilized to proceed with HCT. Our study, though limited in size, provides further compelling evidence that long-term CR, and potentially cure, may be achieved using HCT as a treatment modality.

Disclosures:
No relevant conflicts of interest to declare.
Autologous Hematopoetic Stem Cell Transplantation as An Intensive Consolidation Therapy for Adult Patients in Remission from Acute Myeloid Leukemia.
Authors: Genadieva-Stavrik Sonja G , Pivkova Alexandra , Stojanoski Zlate , Krstevska-Balkanov Svetlana , Georgievski Borce 
Published: October 2019

Abstract
Abstract 4595
Despite advances in our understanding of its pathogenesis, acute myeloblastic leukemia remains difficult to treat. Although initial complete remission can be achieved in a high percentage of patients, relapse occurs in 70–80% of the patients. Two main approaches have been the attempt to eradicate the leukemic clonal cells population via chemotherapy with or without autologous stem cell rescue or to pursue a combined approach using an antileukemic therapy combined with an antileukemic immune response via allogeneic bone marrow transplantation. Autologous transplantation compares favorably against allogeneic bone marrow transplant in several ways. Autologous transplantation can be used as a consolidation therapy in the older population, and lack of a matched donor does not preclude the patients from this treatment.
We report a retrospective analysis on 48 patients diagnosed with de novo AML, who did not have an available histocompatible donor, and who underwent autologous transplantation between years 2000–2009 at the University hematology Clinic, Skopje, Macedonia. All patients had ECOG score 1 or less. The patient's age ranged from 17 to 65 years with the median age 41 years. There were 26 males and 22 females. For stem cell mobilization patients received chemotherapy or chemotherapy plus G-CSF. The preparative chemotherapy regimen prior to autologous transplantation consisted of BuCy in 24 patient, BEAM in 22 and BuCyMel was used in the remaining 2 patients. We used bone marrow as primary source of stem cells in 18 patients, and peripheral blood stem cells in remaining 30 patients.
The five years overall survival was 52% and the 5 years disease progression free survival were 42%. We analyzed sever factors that can influence the overall survival and the disease free survival such as: age, disease status, stem cell source, chemotherapy regiments prior to transplantation, conditioning regiments, number of mobilized stem cells. Advanced age and bone marrow stem cell source seems to be more influent factors.
We report that the clinical results of autologous hematopoietic stem cell transplantation are sufficiently encouraging to warrant future trials that include autologous transplantation as an option for appropriately selected patients with AML in CR1. We conclude that autologous hematopoietic stem cell transplantation is a reasonable and save intensive consolidation for patients with acute myeloblastic leukemia who do not have a suitable HLA–matched donor.

Disclosures:
No relevant conflicts of interest to declare.
Research on the Characteristics of IGHV Gene In Chronic Lymphocytic Leukemia of China.
Authors: Qiao Chun , Miao Kourong , Li Jianyong 
Published: October 2019

Abstract
Abstract 4609

Objective
The usage, mutation status and prognostic impact of immunoglobulin heavy chain variable (IGHV) gene in Chinese patients with chronic lymphocytic leukemia (CLL) is unclear. We set out to define the characteristics of IGHV gene and its relevance to clinical and biological parameter in our patients.

Methods
IGHV gene mutations were detected by multiplex PCR in 202 Chinese CLL patients and the purified PCR amplification products were sequenced. IGHV somatic hypermutation status and gene usage were analyzed by IMGT/V-QUEST software. The association analysis between IGHV somatic mutation status and the clinical and biological features, including Binet staging, immunophenotype, cytogenetic aberrant, were also emphasized in this study.

Results
The results showed that 129 patients had mutated (M) IGHV, and the remaining 73 patients had unmutated (UM) IGHV according to the cutoff value of accordance rate 98%. The most frequent VH gene family was found to be VH3 (47.5%), followed by VH4 (34.7%), VH1 (11.4%), VH2 (2.5%), VH5(1.5%), VH7(1.5%) and VH6(0.9%) gene families, which was similar to other Asian populations. The overall survival (OS) time of UM IGHV group was significant shorter than M IGHV group (P=0.025). Significance was found in the expression of CD38 and ZAP-70 between patients with and without IGHV mutations (P<0.0001 and P=0.015, respectively). Binet staging was significantly different with IGHV mutation status (P<0.001). “Unmutated” sequences had significantly longer heavy chain complementarity-determining region 3 (HCDR3). Seven of these patients used VH1-69, which was similar to other Asia countries, but in striking contrast to those in Western countries, where VH1-69 was one of the most frequently used genes. FISH was performed in 117 cases, del(11q22) was considered as high risk factors, and 10(10/42, 23.8%) cases with UM IGHV gene. On the other hand, there were 7(7/75, 9.3%) cases with M IGHV gene (P=0.033). No significance was found in del(17p),del(13q),del(6q),add(12),IGH translocation between IGHV mutation and unmuatioan patients. A total of five stereotyped BCR were identified, IGHV3-21/IGHD3-9/IGHJ6, IGHV4-34/IGHD2-15/IGHJ6, IGHV1-3/IGHD6-19/IGHJ4, IGHV4-59/IGHD3-22/IGHJ6 and IGHV4-39/IGHD6-13/IGHJ5.

Conclusions
The usage of IGHV gene families indicates significant difference in Chinese CLL patients compared with Western patients, suggesting involvement of ethnic and/or environmental factors in CLL disease initiation. In the development course of CLL, BCR play an important role in the immunological recognition and selection. There are intimate relationships between mutation status of IGHV gene and prognosis. The usage of IGHV provides enlightment for the occurrence mechanism of CLL.

Disclosures:
No relevant conflicts of interest to declare.
Detection of Cytokine Protein Expression In Immune Thrombocytopenic Purpura Using Protein Arrays
Authors: Zou Shan Hua , Zhang Xuejiao , Wang Weiguang , Cheng Yunfeng 
Published: October 2019

Abstract
Abstract 4673

Introduction
Immune thrombocytopenic purpura (ITP) is an autoimmune disease characterized by low platelets and bleeding. The mechanism of ITP has historically been attributed to platelet autoantibody production and the resultant platelet destruction. More recent evidence suggests a multifactorial pathogenesis. Patients show impaired immune regulation manifested by increased proliferation of helper T lymphocytes and cytotoxic T lymphocytes from patients can lyse platelets in vitro. A complex picture of the immune processes involved in autoimmunity has emerged over the last decade with the identification and characterization of immunoregulatory elements (receptors, cytokines, and other signaling molecules) and cell trafficking patterns. Protein arrays are rapidly becoming established as a powerful means to detect proteins, monitor their expression levels, and investigate protein interactions and functions.

Method
During August 2009 to April 2010,17 newly diagnosed patients with ITP were enrolled. The mean platelet count at onset is 25*109/L. Seventeen health adults were as control group. We detected the changes of 507 kinds of cytokines, receptors and other signaling molecules in patients with ITP at onset, remission and relapse using the RayBio® Biotin Label-based Human Antibody Array I. The expression level differed by more than 2-fold from that observed in control group was as abnormal. We analyzed these proteins by cluster analysis.

Results
Compared with the healthy volunteers, the ITP patients at onset showed 35 elevated and 130 decreased proteins, the ITP patients at relapse showed 99 elevated and 189 decreased cytokines, the patients at remission showed 94 elevated and 144 decreased cytokines. This study shown that Th1 cytokines, JAK-STAT signaling pathway molecules, TGF-beta signaling pathway molecules, chemokine signaling pathway molecules, MAPK signaling pathway molecules and TLR signaling pathway molecules maybe closely related to the pathogenesis in ITP.

Conclusion
An understanding of the interplay of cytokines, receptors and signaling molecules in the breakdown of self-tolerance has brought to light unrecognized mechanisms of the autoimmune destruction of platelets in ITP and potential targets for future therapeutic advances. These identified proteins may constitute novel biomarkers of ITP and might hold great potential as surrogate markers for monitoring the patients with ITP.

Disclosures:
No relevant conflicts of interest to declare.
The Importance of a Bone Marrow Biopsy to Distinguish Primary Immune Thrombocytopenia From Indolent Haematological Malignancies
Authors: Gudbrandsdottir Sif , Hasselbalch Hans Carl , Frederiksen Henrik 
Published: October 2019

Abstract
Abstract 4676

Background
Primary immune thrombocytopenia (ITP) is characterised by an immune-mediated destruction of platelets and impaired platelet production [1, 2].
The diagnosis is one of exclusion, and any disorder presenting with isolated thrombocytopenia can mimic ITP [3].

Aims
To identify and describe patients initially diagnosed with ITP and included in an on-going clinical trial, when further diagnostics revealed other underlying disorders as the aetiology to the low platelet counts.

Methods
Patients were identified from the on-going clinical trial ‘A randomised fase III study of the efficacy of rituximab in combination with dexamethasone vs dexamethasone in newly diagnosed patients with ITP’. All patients had given their written informed consent. The diagnosis of ITP was defined as isolated thrombocytopenia, normal bone marrow biopsy, no splenomegaly assessed by ultrasound, normal TSH-levels and exclusion of secondary immune-, viral- or drug-induced thrombocytopenia.
Patients who were enrolled in the study but subsequently diagnosed with other underlying disorders and excluded from the protocol are described in the following.

Results
116 patients had been enrolled in the clinical study at the time of these analyses. 9 patients were subsequently diagnosed with other disorders and excluded from the study.
The median time from inclusion in the ITP-protocol to diagnosis of the underlying disorder was 11 days (range 3 – 486 days).
4 patients were diagnosed with other haematological disorders (debut symptoms, see figure 1).
4 patients with CMV presented median platelet count of 6 ×109/L (range 4–12 ×109/L), petechiae (4 patients) and mucosal bleeding (3 patients). 1 patient had flu-like symptoms and elevated leucocyte count. CMV was diagnosed by positive IgM titer after a median of 17,5 days (range 7 –29).
1 patient was diagnosed with antiphospholipid syndrome 17 days after inclusion. Conclusion
The diagnosis of ITP is one of exclusion, and it is essential that patients presenting with isolated thrombocytopenia be thoroughly tested for underlying disorders. The present study has shown that a bone marrow biopsy may be a prerequisite and the only diagnostic tool to distinguish ITP from MDS or other low-grade malignancies. A bone marrow biopsy is recommended in all elderly patients in whom indolent haematological malignancies initially may mimick ITP.

Disclosures:
Gudbrandsdottir: GlaxoSmithKline: Research Funding; Amgen: Research Funding. Frederiksen:GlaxoSmithKline: Membership on an entity's Board of Directors or advisory committees.
Successful Treatment of An Elderly Patient with Refractory Chronic Immune Thrombocytopenic Purpura with Combination Therapy of Rituximab and Corticosteroids: A Case Report
Authors: Ling Yun , Cao Xiangshan , Qian Xinyu 
Published: October 2019

Abstract
Abstract 4686
Immune thrombocytopenic purpura (ITP) is an autoimmune disorder. A corticosteroid, usually prednisone is often the first line treatment for ITP. However, the problem is that about 70 percent of adult patients experience a relapse after discontinuation of corticosteroids. And approximately 20–30% of patients with chronic ITP do not respond to corticosteroids therapy. Rituximab has been proven effective in refractory chronic ITP, but the timing of response is slower than expected, at least three months might be necessary to observe an effect. And the response duration to rituximab remains relatively short in some patients. So, sometimes it is necessary to use combination therapy including rituximab, according to different patient conditions. Here, we report an 82-year-old man with chronic ITP who had thrombocytopenia (platelet count <10 × 109/L) for more than 6 months and relapsed on a prednisone taper. He presented sustaining blood-tinged sputum, bleeding in skin and steroid-induced diabetes, the result of short-term prednisone. He didn't want splenectomy and other immune suppressive drugs. His blood glucose got control after insulin therapy. We gave the patient intravenous infusions of rituximab 375 mg/m2 weekly for 4 weeks combined with dexamethasone (10 mg intravenously weekly for 4 weeks). After first dose of dexamethasone followed by rituximab, within 24 hours his platelet count had increased to 65 × 109/L and bleeding symptoms were significantly improved. During the next 3-week period of treatment, his platelet counts fluctuated between 30 × 109/L and 60 × 109/L. And then the platelet count dropped back to a minimum of 19 × 109/L. Consider the slow responses to rituximab and prevention of bleeding, we still gave the patient maintenance therapy with 15mg prednisone daily and he had been no bleeding. Two months after starting rituximab and dexamethasone, his platelet counts began to gradually recover to normal. Although we need to further observe the patients's duration of response, this case suggests that combination therapy of rituximab and corticosteroids may be a promising treatment for refractory chronic ITP.

Disclosures:
No relevant conflicts of interest to declare.