bluuebunny/crossref_metadata_2025_split huggingface dataset:
“Lymphomatous and Leukemic Meningitis – Patterns of Cytomorphology and Value of MRI and Protein Analysis”.
Authors: Strik Herwig Matthias , Perske Christina , Proemmel Peter , Nagel Ingelore , Nagel Holger 
Published: October 2019

Abstract
Abstract 5011

Introduction
Lymphomatous and leukemic meningitis (LM), although a well known and relatively frequent complication of aggressive lymphoma and leukemia, are still difficult to detect. With cytomorphology, neoplastic lyphocytes are difficult to distinguish from inflammatory lymphocytes. We evaluated here if specific morphological criteria can improve this differentiation. Moreover, we assessed the sensitivity of MRI and protein analysis for the detection of LM in comparison with CSF-cytology.

Patients and Methods
To establish cytomorphological criteria, 42 cytospin preparations of CSF from patients with confirmed CSF involvement by aggressive lymphoma or acute leukemia were compared with 26 samples of inflammatory diseases. CSF cytology was analyzed morphologically for pre-selected parameters of cell, cytoplasm and nucleic appearance and the presence of mitoses or apoptoses. For the comparison of cytology and MRI, 38 patients with leukemic or lymphomatous meningitis were evaluated retrospectively for MRI-signs of neoplastic meningitis and for CSF-protein abnormalities (total protein, oligoclonal bands, lactate, ferritine).

Results
as expected, none of the cytomorphological parameters sharply discerns neoplastic and inflammatory transformation. However, neoplastic cells were significantly larger than inflammatory lymphocytes with a mean of 3.0 as opposed to 1.8 times the size of normal small lymphocytes (p=0.0001). Moreover, irregular shape, pointed borders of the cytoplasm, and deep notches in the nucleus were significantly more often found with neoplastic than with inflammatory lymphocytes.
The total cell count was elevated in 68% of cases of lymphomatous meningitis. While cytomorphology could achieve approx. 90% sensitivity for the detection of LM, spinal and/or cranial MRI only detected 71% of cases with normal and 52% with elevated cell counts. Total protein was elevated in 77% of cases, lactate in 55% and ferritine in 48%. Oligoclonal IgG was found in 11% isolated in the CSF and in 18% in CSF and serum identically. Only 3/38 patients (8%) had completely normal CSF cell count and proteins.

Conclusions
CSF cytology is more sensitive than MRI for the detection of LM, but application of both methods clearly enhances the sensitivity by approx. 10%. No single cytomorphological parameter is sufficient to detect neoplastic lymphocytes. Considering a combination of cell size and irregular shape of cell and nucleus may improve the diagnostic accuracy of CSF dissemination by aggressive hematological malignancies.

Disclosures
Strik: Mundipharma : Consultancy, Honoraria, Research Funding, Speakers Bureau; Essex/Shering-Plough/Merck: Consultancy, Honoraria, Speakers Bureau; Medac: Research Funding.
FDG-PET for Staging and Follow-up of HIV-Infected Patients with Non Hodgkin Lymphoma and Hodgkin Lymphoma: A Single Center Experience.
Authors: Cantoni Silvia , Ravelli Erika , Moioli Maria Cristina , Rusconi Chiara , Zilioli Vittorio Ruggero , Basilico Claudia Maria , Gargantini Livio , Nosari Annamaria , Volonterio Alberto , Rossetti Claudio , Morra Enrica 
Published: October 2019

Abstract
Abstract 5014

Introduction
Risk of developing non Hodgkin lymphomas (NHL) is known to be increased among patients (pts) infected by HIV-1 and sporadic non-HIV related cases of Hodgking lymphomas (HL) are also described. HIV-positive pts also feature a virus-related systemic lymphoadenopathy which makes nodal involvement by lymphoma difficult to evaluate using conventional imaging. The role of positron-emission tomography using 18F-fluorodeoxyglucose (FDG-PET) in the staging and evaluation of response to treatment of pts with NHL and HL is well established in immunocompetent pts, while only limited information is available on lymphomas arising in the setting of HIV infection. We report on a retrospective analysis of FDG-PET results in a group of HIV pts with lymphoma, both NHL and HL, followed-up at our hospital.

Patients and methods
Twelve HIV-positive male pts with a diagnosis of lymphoma (7 high grade and 1 follicular NHL, 4 HL) underwent a total of 22 PET scans. PET results were compared with those obtained by computed tomography (CT). Nine PET were performed at staging, 7 at restaging following chemotherapy, and 6 at follow-up. At diagnosis of lymphoma: median CD4 count was 200 cells/mcL (range 98-451); HIV genome was undetectable in 5/9 pts, in the remaining 4 pts for whom the data was available viral loads ranged from 103 to 1,452,720 copies/mL; 10/12 pts were already receiving HAART, while the remaining 2 pts started treatment upon diagnosis of lymphoma.

Results
In the majority of cases (17/22 = 77%) results of PET, CT scan and clinical status were concordant, being diagnostic of either lymphoma presence (11/17) or absence (6/17). No false positive results were recorded at follow-up. In 5/22 cases (23%) PET and CT scan were discordant. In 4 cases PET yielded a false negative result; in 2 cases at diagnosis (2 pts with HL) and in 2 cases at follow-up (both in the pt with follicular lymphoma). In the remaining case, a PET-negative CT-positive adenopathy was demonstrated which proved to be reactive in nature at biopsy.

Discussion
Our results suggest that FDG-PET is useful in the evaluation of lymphoma in the setting of HIV infection, similarly to what has been observed among immunocompetent pts. Although the number of patients is limited, in our experience PET proved to be able to discriminate between reactive and lymphomatous involvement of lymphoid tissue as demonstrated by absence of false positive results in pts evaluated at follow-up. These results need to be confirmed by larger clinical trials.

Disclosures
No relevant conflicts of interest to declare.
Ex-Vivo Expanded Peripheral Blood Stem Cells (EVEC) Compared with Un Manipulated Peripheral Blood Stem Cells (PBSC) Autologous Transplantation for Multiple Myeloma: A Pair Match Analysis.
Authors: Milpied Noel-Jean , Marit Gerald , Dazey Bernard , Boiron Jean-Michel , Ivanovic Zoran , Foucaud Carine , Bijou Fontanet , Bouabdallah Krimo , Schmitt Anna , Sauvezie Mathieu , Cailliot Christian , Reiffers Josy 
Published: October 2019

Abstract
Abstract 502

Autologous stem cell transplantation with PBSC after high-dose chemotherapy remains standard therapy for patients with symptomatic Multiple Myeloma (MM). Strategies to minimize complications could significantly reduce the morbidity of that procedure. One possibility could be to shorten the duration of induced neutropenia through the injection of an ex-vivo expanded graft. Nineteen patients (pts) received EVEC after high-dose Melphalan (HDM) (200 mg/m2) as the only graft. The ex-vivo expanded procedure has been described elsewhere (Boiron et al. Transfusion 2006 and Ivanovic et al. Transfusion 2006). Briefly, thawed peripheral blood CD 34+ cells collected after G-CSF mobilisation and selected with immunomagnetic devices were incubated for 10 days in a serum free medium (Maco Biotech HP01) with Stem Cell Factor (Amgen), G-CSF (Amgen) and TPO (Amgen: 7 pts; Cellgenix:12 pts). The expanded cells were then thoroughly washed and injected 48h after the HDM injection. The ex-vivo expansion lead to a median fold of 5,4 for CD34+ cells (1,3-11,8); 118 for CD33+ (1-703880); 3386 for CD14+ (4-101075); 28,5 for CD13+ (10-703880) and 13 for CFUs (6-21). The median N° of CD34+ cells injected was 14×10e6/kg (5,3-48). The results of these transplants were compared to those achieved in 38 pts who received unmanipulated PBSC after HDM. Pts and controls were matched for age, sex, stage of the disease, first line chemotherapy ( VAD or VD) status of the disease at time of transplant, year of transplant, time between diagnosis and transplant, CD34+ mobilisation technique (HD cytoxan + G-CSF or G-CSF alone) and the median N° of total nucleated cells and of CD34+ collected. The results are summarized on the table:
There was no secondary neutropenia in the patients who received EVEC. With a median FU of the entire cohort of 30 m, the median OS for pts who received their first transplant with EVEC and with PBSC is 69 m and not reached respectively (p=NS), the median PFS is 18 m and 27 m (p = NS) and the median time to progression is 14 m and 15 m (p=NS).

Conclusion:
EVEC is feasible, safe and reduce significantly the morbidity of autologous stem cell transplantation after HDM for multiple myeloma.

Disclosures:
Milpied: Amgen France: Honoraria.
Adaptor Protein Lnk Binds to JAK3 and Negatively Regulates a Mutant Activating Allele Associated with Megakaryocytic Leukemia.
Authors: Koren-Michowitz Maya , Gery Sigal , Nowak Daniel , Koeffler Phillip H 
Published: October 2019

Abstract
Abstract 5044
The adaptor protein Lnk is known to associate with hematopoietic cytokine receptors such as cKIT, MPL and PDGFR, as well as, non-receptor tyrosine kinases such as JAK2, and is considered to have an inhibitory effect on these signaling pathways. JAK3 is expressed mainly in the hematopoietic system and its absence is associated with autosomal recessive severe combined immunodeficiency (SCID). Recently, activating mutations of JAK3 were described in transient myeloproliferative disorder (TMD) and acute megakaryocytic leukemia (AMKL) in Down syndrome (DS) patients as well as adult non-DS AMKL. JAK3 mutations were also rarely described in solid tumors and B-ALL. The 50% homology between JAK3 and JAK2 has led us to study the association between Lnk and JAK3.293T cells were co-transfected with cDNAs encoding either wild-type (WT) JAK3 or JAK3 harboring an activating A572V mutation (JAK3 A572V), as well as the WT V5-tagged Lnk. Whole cell lysates were used for immunoprecipitation with either V5-tag or JAK3 antibodies. Binding of Lnk and JAK3 was detected by Western blot probed with JAK3 or V5-tag antibodies. To determine which domain of Lnk is responsible for the binding, we constructed a series of V5-tagged Lnk mutants including a mutation in the SH2 domain (R392E), deletion of the SH2 domain (del SH2) and deletion of the PH and SH2 (del SH2/PH) domains. Our results show that WT Lnk binds to WT JAK3, as well as JAK3 A572V. The R392E and del SH2 Lnk mutants retained JAK3 binding capacity while deletion of both SH2 and PH domains of Lnk abolished JAK3 binding. In order to study the biological effect of Lnk binding to JAK3, we infected CMK cells, a megakaryocytic leukemia cell line harboring JAK3 A572V, with a bicistronic retroviral MSCV-IRES-GFP (MIG) WT Lnk vector. Effect on growth was assessed in GFP positive sorted cells by cell count and colony formation in methylcellulose. CMK cells infected with MIG WT Lnk grew slower in liquid culture and had decreased clonogenic growth in soft agar culture compared to cells infected with MIG vector alone.
In summary, we show for the first time that Lnk can bind to WT and mutant JAK3 and slow the growth of leukemic cells harboring an activating JAK3 mutation. Developing a small molecule mimetic of Lnk may have a therapeutic role in the treatment of hematopoietic malignancies associated with a variety of activated tyrosine kinase receptors and non-receptor tyrosine kinases including JAK3, as well as secondary signaling proteins.

Disclosures
No relevant conflicts of interest to declare.
The Effect of siRNA Down-Regulating XIAP On the Apoptosis and Chemo-Sensitivity of K562 Cells in Vitro.
Authors: Xie Shuangfeng , Yin Songmei , Li Dan , Nie Danian , Li Yiqing , Ma Liping , Wang Xiuju , Xiao Jie 
Published: October 2019

Abstract
Abstract 5053

Introduction
Failure for chemotherapy in leukemia patients is often due to innate or acquired multi-drug resistance of leukemia cells. The X-linked inhibitor of apoptosis protein (XIAP) is a potent inhibitor of apoptosis and is also involved in drug resistance. The relationship between XIAP and drug resistance is not fully clarified. Here, we manipulated the expression of XIAP in K562 human chronic myelogenous leukemia cells and explore the changes in cell apoptosis and sensitivity to cytarabin.

Methods
Small interfering RNA (siRNA) targeting XIAP was created, K562 cells were either transfected with XIAP siRNA or control siRNA by Nucleofector transfection. The siRNAs were labelled with Cy3. Real-time RT-PCR and Western blot were used to determine the expression of XIAP in K562 cells. Flow cytometry was used to detect apoptotic cells and 50% inhibiting concentration (IC50) of cytarabin was also determined.

Results
The transfection rate was 87% in general. The transfection was also confirmed by fluorescence microscopy. After 48h, the expression levels of XIAP mRNA and protein were much lower in XIAP siRNA-transfected cells than in control siRNA-transfected cells (mRNA, 0.37±0.10 vs. 1.41±0.13, P<0.05 ; protein, 0.39±0.03 vs. 0.99±0.08, P<0.05). There was no significant difference in the fractions of apoptotic cells between these two groups at 48h after transfection (37.04%±1.77% vs. 47.43%±1.13%, P>0.05). Cytarabin was added in different concentrations right after Nucleotransfection. After 48h, the IC50 of Cytarabin in the XIAP siRNA-transfected cells was 2.28-fold lower than that in the control siRNA-transfected cells (82.60±21.56μg/ml vs. 188.67±44.48μg/ml, P<0.05). The percentage of apoptotic cells was much higher in the XIAP knockdown cells than in the control cells (47.43%±1.13% vs. 37.04%±1.77% P<0.05).

Conclusions
XIAP siRNA can specifically down-regulate the expressions of XIAP mRNA and protein, promote the drug-sensitivity to cytarabin and increase the cell apoptosis in K562 cells. This might be a novel choice for leukemia treatment.

Disclosures
No relevant conflicts of interest to declare.
Pediatric Venous Thromboembolism: Redefining Epidemiology.
Authors: Setty Bhuvana A , O'Brien Sarah H. , Kerlin Bryce A. 
Published: October 2019

Abstract
Abstract 5055

Introduction
Pediatric venous thromboembolism (VTE) is a multifactorial disease most commonly seen in children with complex medical conditions. The data regarding associated conditions in children is sparse. The most comprehensive source regarding these associations is derived from the Canadian registry of 137 children with VTE collected from 1990-1992.

Objective
To refine the spectrum of pediatric VTE associated illnesses, utilizing a large, comprehensive claims database.

Methods
The Healthcare Cost and Utilization Project (HCUP) Kids' Inpatient Database (KID) 2006 was utilized to identify children <18 years old with in-hospital VTE. These children were identified by the presence of at least one of the following ICD-9-CM diagnosis or procedure codes: 325, 452, 453(.0, .2-.42), 453 (.8-.9), 415 (.0-.11), 38 (.05, .07, .09), or 99.10. The remaining diagnostic ICD-9-CM codes were then utilized to assign a preliminary Complex Chronic Condition (CCC) category for each patient, using previously defined criteria. This categorization was further refined by a manual translation of the diagnostic codes by one of the investigators (BAS or BAK). The incidence of in-hospital VTE by geographic region, hospital type, age, gender, ethnicity, and median household income was estimated.

Results
4,731 children met the inclusion criteria (1.76/1,000 discharges). The major underlying illnesses were cardiovascular (18%), malignancy (17%), neuromuscular disease (11%), gastrointestinal (8%), hematology/immunology (7%), and metabolic disease (6%). Trauma and surgical interventions were present in 5 % while 5% of VTE was idiopathic. Renal, respiratory, and autoimmune diseases were less commonly associated with VTE (<5%). Interestingly, the incidence of VTE was highest in the Midwest (2.12/1,000 discharges) and lowest in the South (1.60/1,000 discharges). As seen in previous studies, VTE was more commonly seen in infants and adolescents. There was a slight predominance of males with VTE (1.22:1). 4.2% of the VTE were associated with in-hospital death.

Conclusion
Pediatric VTE is rarely an idiopathic illness. More commonly it is associated with a chronic underlying medical condition. These data refine our understanding of the spectrum of underlying health conditions in children with VTE. This is limited by the inability to take into account the use of various medications and outpatient interventions that may have contributed to the occurrence of the VTE. Future studies should focus on the epidemiology of VTE within each associated disease category.

Disclosures
No relevant conflicts of interest to declare.
Evaluation of the Gene Encoding Calcium Diacylglycerol Guanine Nucleotide Exchange Factor I (CalDAG-GEFI) in Human Patients with Congenital Qualitative Platelet Disorders.
Authors: Puetz John , Boudreaux Mary 
Published: October 2019

Abstract
Abstract 5078
Normal platelet function is dependent on an orchestrated series of interactions resulting in primary hemostasis. Dysfunction in any step of platelet activation and aggregation results in abnormal platelet function and abnormal mucocutaneous bleeding. Defects in agonist/receptor interactions, membrane phospholipid and cytoskeleton structure, signal transduction, storage pool content and release have all been described. While some congenital qualitative platelet function disorders such as Bernard-Soulier syndrome or Glanzmann thrombasthenia are well characterized at the molecular and genetic level, the majority of congenital platelet function disorders are not. Recently, insights into the molecular and genetic causes of platelet signal transduction and secretion pathway disorders have been found in animals. Dogs and cattle with recurrent abnormal mucocutaneous bleeding symptoms and abnormal in vitro platelet aggregation have been found to be caused by a mutation in the calcium-diacylglycerol guanine nucleotide exchange factor I (CalDAG-GEFI) gene. Genetic ablation of CalDAG-GEFI in mice has resulted in abnormal platelet function and bleeding. Polymorphisms in the human CalDAG-GEFI gene have been linked to Kindlin-3/ FERMT3 mutations resulting in a leukocyte adhesions defect associated with platelet dysfunction (LAD-III or LAD-1/variant syndrome). To date, mutations in the CalDAG-GEFI gene in humans associated with abnormal platelet function and bleeding have not been described. To determine if mutations in the human CalDAG-GEFI gene are associated with abnormal mucocutaneous bleeding and platelet aggregation dysfunction, we have begun sequencing the CalDAG-GEFI gene in human patients with a congenital qualitative platelet function disorder of unknown etiology. As control groups, we will also evaluate the CalDAG-GEFI gene sequence of unaffected family members and unrelated blood donors known to have normal platelet aggregation. Preliminary results of our analysis will be presented.

Disclosures
No relevant conflicts of interest to declare.
Association of Red Blood Cell Distribution Width (RDW) with Laboratory Parameters in Anemic Adults.
Authors: Means Robert T. 
Published: October 2019

Abstract 5083
RDW, a quantitative measure of anisocytosis, has been utilized for many years in the differential diagnosis of anemia. More recently, studies have reported that RDW varies with renal function and markers of inflammation, and that RDW is a predictor of mortality (Scand. J. Clin. Lab. Invest. 2009; 68:745-8; Arch. Pathol. Lab. Med. 2009; 133:628-32; Arch. Intern. Med. 2009; 169:588-94). However, these reports were based on studies of large populations of unselected outpatients, many of whom were hematologically normal. Utilizing a de-identified database of 32 anemic adult inpatients (17 male/15 female, 27 Caucasian) who had undergone diagnostic bone marrow examination as part of an earlier study (J. Clin. Lab. Haematol. 1999; 21:161-7), associations between RDW and clinical laboratory parameters in a more restricted patient subset were examined.
RDW values for 26/32 patients were in the highest quintile observed in the National Health and Nutrition Examination Survey (RDW > 13.8%). Significant differences between patients in the highest quintile and other patients were observed for hemoglobin concentration (9.9 g/dL vs. 11.6 g/dL, p = 0.01), serum soluble transferrin receptor (sTfR) (30.3 nM vs. 16.7 nM, p = 0.02), and serum interleukin (IL)-1 (1.6 pg/mL vs. 0.3 pg/mL, p =0.03). No other significant differences were observed in other automated hematologic markers, in biochemical indicators of iron status, renal function, or inflammation, or in marrow aspirate iron score. When the correlation between RDW and the other parameters studied was evaluated, the only statistically significant correlations found were with C-reactive protein (CRP) (r = -0.49, p = 0.009) and sTfR (r = 0.53, p = 0.002). The significance of the correlation between sTfR and RDW was independent of other indicators of iron status, CRP, and serum IL-1. In contrast, the significance of the correlation between CRP and RDW was dependent on variation in sTfR and serum ferritin concentrations. In this group of patients with who generally had either high-normal or high RDW values, CRP and RDW were inversely correlated.
In summary, associations between RDW and other laboratory or clinical parameters observed in unselected patient populations may not be applicable to complex anemic inpatients. The association between sTfR concentration and RDW appears to be independent of the relationship between sTfR concentration and patient iron status.

Disclosures
Means: Beckman Coulter, Inc.: Consultancy, Honoraria.
Haploidentical Hematopoietic Stem Cell Transplantation for Non-Hodgkin's Lymphoma with Bone Marrow Involvement.
Authors: Wang HengXiang , Xue Mei , Liu Jing , Yan Hong-Min , Duan Lian-Ning , Zhu Ling , Wang Zhi-Dong 
Published: October 2019

Abstract
Abstract 5124
Here, we report the preliminary results of haploidentical hematopoietic stem cell transplantation (Haplo-HSCT) with G-CSF mobilized bone marrow grafts without T cell depletion for 10 cases with refractory non-Hodgkin's lymphoma accompanied by bone marrow involvement. The patients were aged ranging 7 to 38 years and six were of T- and four were B-cell origin at diagnosis. Eight patients received a conditioning regimen consisting of high-doses of cytarabine and cyclophosphamide with total body irradiation, while two cases busulfan, thiotepa and cyclophosphamide. All patients had rapid engraftment with the mean time for neutrophil and platelet recovery was 16.6 days and 19.2 days, respectively. Three cases died within six months after transplantation from severe acute graft-versus-host disease, fungal infection or relapse. The others are currently alive at a median follow-up of 60.7 months (range: 44-81months). Therefore, haplo-HSCT might provide an opportunity of myeloablative therapy for refractory lymphoma with bone marrow involvement.

Disclosures
No relevant conflicts of interest to declare.