bluuebunny/crossref_metadata_2025_split huggingface dataset:
Post-Thaw Viability of Cryopreserved Hematopoietic Progenitor Cell Grafts Influences Patients' Predisposition towards Infectious Complications in the Post-Transplant Period.
Authors: Vrhovac Radovan , Peric Zinaida , Jurenec Silvana , Kardum-Skelin Ika , Jelic-Puskaric Biljana , Siftar Zoran , Mesaric Jasna , Minigo Hrvoje , Jaksic Branimir 
Published: October 2019

Abstract
Abstract 4666
Cell viability in peripheral blood progenitor cell (PBPC) grafts and its influence on the clinical course following transplantation was evaluated in 81 consecutive transplantations (72 autologous, 9 allogeneic) performed in patients with hematological diseases. Viability of cells in PBPC grafts, assessed by trypan blue dye exclusion test immediately upon collection was 98.6±3.5%, after addition of dimethyl sulfoxide (DMSO) 73.3±21.8%, and post-thaw 65.2±16.1%. It did not differ significantly between patients with different diagnoses, gender, age, type of priming used, dose of G-CSF administered or number of CD34+ cells collected. However, grafts stored for more than 60 days showed lower post-thaw viability compared to the ones thawed in the 60 days following cryopreservation (56.6±15.2% vs. 67.6±15.5%, p=0.04). A strong, statistically significant correlation was found between pre-cryopreserved CD34+ cell dose and hematopoietic recovery in patients, expressed as time to reach ANC>1×109/l and platelets >20×109/l (R2=0.14 p=0.001, R2=0.12 p=0.005, respectively). Occurrence of febrile neutropenia and total number of febrile days did not differ significantly between patients depending on the dose of CD34+ cells infused. On the contrary, post-thaw graft viability did not influence engraftment time, but there was a predisposition towards infectious complications in the post-transplant period in patients receiving grafts with lower percentage of viable cells. These patients developed febrile neutropenia more often (72.2% vs. 50% of patients, p=0.05) and had more febrile days (2.4±2.6 vs. 1.5±2.3, p=0.05) following transplantation. Our results demonstrate that PBPC grafts are capable of long term engraftment regardless of the graft storage time or percentage of viable cells post-thaw, which confirms the robustness of CD34+ cells during the freeze/thaw procedures carried out in daily clinical practice. Granulocyte concentration in PBPC grafts could have an influence on infectious complications following transplantation. This is an intriguing finding that deserves further investigation on a larger number of patients, less heterogeneous in terms of underlying disease, type of transplantation or conditioning regimen used.

Disclosures:
No relevant conflicts of interest to declare.
HHV-6 Encephalitis in Pediatric Unrelated Umbilical Cord Blood Transplantation: Role for Ganciclovir Prophylaxis?
Authors: Cheng Frankie Wai Tsoi , Lee Vincent , Leung Wing Kwan , Chan Paul Kay Sheung , Leung Ting Fan , Shing Matthew MK , Li Chi Kong 
Published: October 2019

Abstract
Abstract 4667

Background
The role of ganciclovir as HHV-6 prophylaxis in unrelated hematopoietic stem cell transplant (HSCT) setting remains controversial.

Methods
We performed a 8-year retrospective review of patients received unrelated HSCT from January 2000 to September 2008. From January 2002, ganciclovir prophylaxis 5mg/kg twice daily for 7 days for all unrelated HSCT before transplant was adopted. The other transplant policies including antibacterial, antifungal, antiviral and graft-versus-host disease control policies remained unchange in that period. The prevalence of HHV-6 encephalitis was studied before and after the change in policy.

Result
Fifty-four unrelated HSCT were performed from January, 2000 to September, 2008. Total four cases (7.4%) of HHV-6 encephalitis were diagnosed. Two cases out of 16 cases (12.5%) diagnosed before adoption of the policy; 2 cases out of 38 cases (5.3%) diagnosed afterward. All of them were unrelated umbilical cord blood (UCB) transplant recipients. Two cases had significant residual neurological deficit and refractory seizure. The other two cases died of other transplant-related mortalities.

Conclusion
We conclude that HHV-6 encephalitis is still a rare complication of unrelated HSCT and may be more common in unrelated UCB transplantation. Routine use of ganciclovir as HHV-6 prophylaxis in all unrelated HSCT recipients may not be justified.

Disclosures:
No relevant conflicts of interest to declare.
Pulmonary Infection After Allo-Transplantation: Fungus or Tuberculosis? 2 Case Report.
Authors: Yin Songmei , Xie Shuangfeng , Li Yiqing , Nie Danian , Wang Xiuju , Ma Liping , Xiao Jie 
Published: October 2019

Abstract
Abstract 4671

Introduction
Infection after allo-Stem cell transplantation (SCT) is a major cause for post allo-SCT deaths. The pathogens involved are diverse and sometimes difficult to be distinguished. Treatment is primarily based on clinical history, blood analysis, chest X-ray, computerized tomography (CT) examination and pathogen culture of sputum or bronchoaleolar lavage fluid. Empirical treatment is often used before the results of pathogen culture are available. Here, we reported 2 cases of allo-SCT with similar clinical background but infections due to different pathogens.

Clinical information
At the onset of the pulmonary diseases, anti-GVHD drugs (Including prednisone, CsA) were already withdrawn for both cases. There was no GVHD progression after withdrawal of the anti-GVHD drugs. Both cases had fever, ranging from 38 to 39 centigrade. Patients were short of breath. Oxygen inhalation was needed. Case 1 was in severe hypoxia. The oxygen saturation was down to 70%∼80% at the peak severity. Neither of the 2 cases was in need of mechanical ventilation. CT images showed that these 2 cases had similar lung injuries (Fig 1 and Fig 2). Tissue biopsy revealed that different pathogens were involved in these 2 cases, although they had identical disease history, similar duration after transplantation, same clinical symptoms and signs, even similar CT images. The histological findings of lung biopsies showed that the pathogen for case 1 was aspergillums, whereas that of case 2 was tubercle bacillus. Both cases responded well to the specific treatment, respectively. Patients are now in disease-free state.

Conclusions
Both tuberculosis and fungus infection could show diffused foci on CT image. The diffused lesions of tuberculosis tend to fuse, whereas little cavities were more frequently seen in fungus infections. After treatment, the lesions of fungus were much easier to be clear than tuberculosis. Diagnostic treatment might be used to distinguish these 2 diseases if biopsy cannot be performed or pathogen culture is negative.

Disclosures:
No relevant conflicts of interest to declare.
CHILDHOOD Biphenotypic ACUTE LEUKEMIA with High Incidence of Basophilic Differentiation: The CONTRIBUTION of Ultrastructural Methods to Diagnosis.
Authors: Resnitzky Peretz , Luria Drorit , Shaft Dina , Avrahami Gali , Jeison Marta , Stark Batia , Yaniv Isaac 
Published: October 2019

Abstract
Abstract 4698
The diagnosis of Biphenotypic Acute Leukemia (BAL) is still a challenge in clinical hematology. In spite of the use of the score formulation of the European Group for the Immunological Classification of Leukemias (EGIL) there are still cases difficult to define. We assessed the contribution of ultrastructural morphology and cytochemistry to the diagnosis of BAL in pediatric leukemic patients. Twenty six patients diagnosed at Schneider Children's Medical Center of Israel between the years 1989 to 2004 have been classified as BAL in a retrospective analysis evaluated by various combinations of light-microscopy (LM) morphology, immunophenotype flow-cytometry, cytogenetics and electron-microscopy (EM) including myeloperoxidase (MPO) and platelet peroxidase (PPO) reaction. The identification of myeloid features by EM was based on the presence of 1) MPO positive granules and MPO reactivity in the nuclear membrane, profiles of endoplasmic reticulum (ER) and in the membranes of the Golgi system; 2) PPO reaction in the nuclear membrane and profiles of ER, and 3) the presence of primary basophilic granules in the cytoplasm of the blasts. The EGIL scoring system has been used with the addition of the ultrastructural findings for the definition of BAL. In 24 cases the morphologic appearance and cytochemistry by LM of the leukemic cells were that of undifferentiated blasts. By cytogenetic evaluation abnormal karyotypes were detected in 16 patients, normal in 4 and unknown in 6 patients. Out of 26 patients 15 had the combination of T-ALL with myeloid phenotype and 11 had the B-lineage with myeloid features. Unexpectedly the blasts of 9 of the 26 BAL patients had basophilic differentiation as indicated by the presence of typical primary basophilic granules with MPO reactivity in a scattered pattern as previously reported in basophylic leukemia. Interestingly 7 of these 9 cases had a T lymphoid component. By contrast among 15 patients who had FAB M0, 9 had the B lineage markers. The remaining 2 patients had M1 and M7 features with T lymphoid phenotype. The contribution of EM studies enabled to establish the diagnosis of BAL in 11 out of 26 patients, in other 6 patients it allowed for the refinement of the AML subgroup such as basophilic leukemia and in the remaining 9 patients EM confirmed the diagnosis of BAL as defined by flow cytometry.

Conclusions
Our study identified a subgroup of children with acute leukemia in whom BAL could be suggested only by the addition of ultrastructural studies. EM could further refine and confirm the diagnosis of BAL in all the other cases. Of interest is the high incidence of basophylic differentiation among BAL pediatric patients, and its association with T lymphoid phenotype.

Disclosures:
No relevant conflicts of interest to declare.
Molecular Profiling of Cancer Testis Antigens in Chronic Lymphocytic Leukemia.
Authors: Dubovsky Jason A , Berchmans Emmanuel , Powers John J. , Hui-Yi Lin , Gao Yang , Sotomayor Eduardo , Pinilla Javier 
Published: October 2019

Abstract
Abstract 4701

Background
Chronic Lymphocytic Leukemia (CLL) is characterized by the progressive accretion of long-lived mature B-lymphocytes. Although the classical Rai and Binet staging is still commonly used, a new molecular understanding has identified specific signatures which could help predict disease progression and survival. Given the recent success of immunotherapeutic strategies and immunomodulatory drugs in the treatment of CLL we sought to identify potentially immunologically relevant targets and their relation to well known disease criterion.

Methods
Our study characterized the mRNA expression of 29 known cancer-testis antigens (CTAs) in 66 patients with CLL at varying stages of disease using a RT-PCR based expression panel. Relevant clinical criterion such as RAI stage, B2m, ZAP-70, IGVH mutational status, CD38, cytogenetics by FISH analysis, WBC count, age, gender, and treatment among others were then taken into account. The binary RNA expression data associated with the clinical and demographic factors were evaluated using chi-square or Wilcoxon rank sum analysis.

Results
Of the cancer-testis antigens tested, the MAGE family of CTAs revealed statistically significant correlations with multiple clinical criteria. Our analysis reveals a correlation between previous chemo-immunotherapy treatment and MAGE-A1, B2, E1, MAD-CT-2, SPA-17, and PAGE-5 expression. Beyond treatment, total white blood cell count was shown to have a significant association with MAGE family members A1, A3, and B2 expression. In addition, MAD-CT-2 and MAGE-B2 were significantly correlated with the expression of FMC-7 and SSX-4 and LAGE-1 correlated with the presence of B-cell symptomatology.

Conclusions
Preliminary RT-PCR based CTA phenotyping has unveiled interesting correlations to clinical criteria, opening multiple avenues for future immunotherapeutic interventions as well as possible prognostic value in CLL. Further investigation to better understand the biological value of this information in warranted.

Disclosures:
Pinilla: Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Bristol-Myers Squibb: Research Funding; exelixis: Research Funding.
Application of SENP-1, HIF-1α and VEGF Gene Expressions in Prognostic Prediction for Normal Karyotypic Acute Leukemia Patients with NPM1 + and FLT3-ITD-.
Authors: Huang Binbin , Xiu Bing , Liang Aibin 
Published: October 2019

Abstract
Abstract 4723
In our study, 26 BM species from 23 normal karyotypic acute leukemia patients (non-APL) with NPM+ and FLT3-ITD- gene mutation were collected in our department. Compared to healthy controls, SENP1, HIF-1alpha and VEGF mRNA expression in ALL and AML patients were elevated to 10.0, 13.2, 16.6 and 43.1, 97.75, 240.0 folds, respectively, by RT-real time PCR. The levels of SENP1, HIF-1αand VEGF mRNA in AML patients were greatly higher than those in ALL (p<0.05). SENP1 and HIF-1alpha expression levels were positively and significantly correlated (linear regression analysis, r = 0.88, p<0.05) both in ALL and AML. The correlation between HIF-1alpha and VEGF mRNA level was statistically significant (linear regression analysis, r = 0.34, p<0.05). Among AML patients, SENP1, HIF-1alpha and VEGF gene expressive level in non-response (NR) patients (n=7) were higher than patients with CR (n=9), p<0.01. For ALL patients, the expressive level (‘X±S) of SENP1, HIF-1alpha, VEGF gene in NR(n=3)were slightly higher than those in CR (n=4): 10.5±2.7, 6.8±3.4; 13.2±16.6, 3.9±3.0; 13.1±10.1,11.1±12.1. Elevated gene expression of SENP1, HIF-1alpha and VEGF indicate shorter survival time of patients, p<0.01.The levels of SENP1, HIF-1alpha and VEGF gene decreased after treatment in 3 AML patients. Thus, higher SENP1, HIF-1alpha and VEGF gene levels might be associated with shortened survival and worse clinical process. Therefore, although higher expression of SENP1, HIF-1alpha and VEGF gene might throw an impact on the prognostic prediction in acute leukemia patients, confirmation of this hypothesis need to be done in more large population.

Disclosures:
No relevant conflicts of interest to declare.
Viral Antigens Trigger Granzyme B Secretion by Human CD5+ B1 Cells in the Presence of Interleukin 21.
Authors: Sontheimer Kai , Blackwell Sue , Hagn Magdalena , Ebel Verena , Beyer Thamara , Simmet Thomas , Jahrsdoerfer Bernd 
Published: October 2019

Abstract
Abstract 4729
CD5+ B1 cells are thought to play a key role in innate immune responses by producing and secreting natural immunoglobulins, which bind to a wide range of bacterial, viral antigens as well as auto-antigens. Here we demonstrate that B1 cells from human cord blood are able to express the pro-apoptotic serine protease granzyme B (GrB) in response to viruses including tick-borne encephalitis virus, rabies virus, and hepatitis B virus. Using pharmacological tools we reveal that this response depends on B cell receptor stimulation, toll-like receptor 9 engagement and interleukin 21 (IL-21), a cytokine primarily found in the acute phase of viral infections. While up to 35% of freshly isolated B1 cells directly respond with GrB expression to stimulation with inactivated viruses in the presence of IL-21, similar, though lower reactions in CD5- B2 cells are only found after, but not before vaccination of the donor against the respective virus. Of note, GrB-expressing B1 cells feature a homogeneous CD19+CD5+GrB+CD20+CD27-CD38-IgD- phenotype and B1 cell-derived GrB is secreted in an enzymatically active state, reaching levels comparable to those secreted by activated cytotoxic cells. GrB induction requires activation of similar signaling pathways as in CTL and NK cells including members of the JAK/STAT pathway. Our findings suggest GrB secretion by B1 cells represents a novel innate immune response mechanism. GrB-secreting B1 cells may play a role in early anti-viral immune defense, and may contribute to elevated serum GrB levels found in various viral diseases. Further studies will elucidate whether CD5+ B1 cells, possibly in co-operation with NK cells, exhibit cytotoxicity towards virus-infected as well as tumor cells.

Disclosures:
No relevant conflicts of interest to declare.
Prognostic Implications of Procalcitonin and NT-ProBNP in Neutropenic Patients.
Authors: Young Kim Sun , Han Hye Young , Jeong Dae-Chul 
Published: October 2019

Abstract
Abstract 4743

Background
Procalcitonin (PCT) has been increasingly used as an inflammatory marker to identify patients with systemic infection. N-terminal pro brain natriuretic peptide (NT-proBNP) elevation can be used to predict future cardiac events and survival. The aim of this study was to evaluate the role of PCT and NT-proBNP measurements in febrile neutropenic patients in terms predicting outcomes in these patients.

Methods
Neutropenia was defined as neutrophil count of 500 cells/mm3 or less or a count of < 1,000 cells/mm3 with a predicted decrease to < 500 cells/mm3. Fever in a neutropenic patient is defined as a single measurement of oral temperature of more than 38.3 °C or a temperature of 38.0 °C for 1 hr. From July 2008 and May 2009, immunocompromized patients with neutropenia were screened for PCT, NT-proBNP at the time of diagnosis, 3 days later and 3 days after fever subsided.

Results
A total of 32 patients aged between 2.5 and 13.5 years (17 boys and 15 girls) were admitted because of neutropenic fever at the Chungnam National University Hospital. PCT levels were not significantly different among 3 different times of measurements, but NT-proBNP was significantly higher at 3 days after admission compared with those of at diagnosis and after fever was subsided. PCT and NT-proBNP levels at the time of diagnosis were significantly correlated with each other. Three patients with higher NT-proBNP showed symptoms of heart failure and arrhythmia but PCT was not significantly elevated in these patients.

Conclusion
PCT and NT-proBNP at the time of diagnosis were correlated with each other. PCT levels were not significantly changed among 3 different times of measurements but NT-proBNP was significant index of heart failure especially 3 days after fever developed.

Disclosures:
No relevant conflicts of interest to declare.
Mathematical Modeling in Optimizing Methotrexate-Based Chemotherapy.
Authors: Kasenda Benjamin , Rehberg Marcel , Franzem Melanie , Fritsch Kristina , Markert Anna , Finke Jürgen , Lebiedz Dirk , Illerhaus Gerald 
Published: October 2019

Abstract
Abstract 4766

Introduction
Optimization of doses and administration schedules for anticancer drugs is crucial for effective and safe treatment. Since chemotherapy (CT) remains based predominately on empiric data, the creation of a mathematical model describing the complex interplay between dosing, tumor-response, agents' clearance, and toxicity, presents the opportunity to optimize treatment strategies of established but also new drugs. Primary central nervous system lymphoma (PCNSL) is a rare disease whose incidence is rising. Standard treatment of methotrexat (MTX) based CT has been approved in several studies. Here we report the most recent development of a real-life mathematical model describing the relationship between MTX serum levels and myelosuppression to optimize current treatment protocols.

Materials and Methods
We retrospectively analyzed 38 patients (pts) diagnosed and treated for PCNSL from 2005-2009. Pts <65 yrs of age were treated according to the high-dose MTX induction protocol (MTX 8g/m2/4hrs followed by leucovorin rescue), whereas treatment of pts >65 yrs of age followed the elderly protocol (MTX 3g/m2/4hrs followed by leucovorin rescue). Leukocyte and MTX serum levels were documented. We used an extended version of the mathematical model by Friberg et al. (J Clin Oncol 2002) as basis for our computations. The model was fitted to the data by using a least-squares-error approach.

Results
First order elimination proves sufficient for describing the pharmacokinetics of MTX. The average elimination rate is 0.25 h-1 with similar inter-patient and inter-therapy variation: the STD is 0.03 h-1 among patients and 0.02 h-1 among treatments. Similar analysis of all present parameters highlights the overall robustness of our approach.

Conclusion
Our model makes it possible to predict myelosuppression after treatment with MTX following leucovorin rescue based on clinical data. The parameters estimated are in accordance with those provided by Friberg et al. and thus confirm the model's general relevance. Extensions of the model describing tumor size reduction by MTX will be implemented to describe the complex interplay between MTX serum levels, clearance and anti-tumor effect. Additionally, mathematical optimal control theory methods will be employed to compute optimized schedules, i.e. doses and timing for the drugs that minimize tumor size and do not violate toxicity constraints such as leukocyte count.

Disclosures:
No relevant conflicts of interest to declare.
LATE EFFECTS IN Hodgkin's POPULATION Treated BETWEEN 1980-2005 IN A SINGLE INSTITUTION.
Authors: Gini Guido , Caraffa Patrizia , Offidani Massimo , Trappolini Silvia , Bocci Caterina , Stronati Andrea , Corvatta Laura , Polloni Claudia , Gentili Silvia , Savini Agnese , Montanari Mauro , Capelli Debora , Poloni Antonella , Olivieri Attilio , Leoni Pietro 
Published: October 2019

Abstract
Abstract 4769
From 1980 to 2005 in our institution we've diagnosed and treated 361 patients (pts) affected by Hodgkin's disease. At the moment of diagnosis the median age of the patients was 29 years (range 13-69).About 72% of patients were in the stage I-II and 28% were in the stage III-IV. More than 54% of all patients received ABVD, 17% received MOOP, 10% MOOP/ABVD, 3% VBM and 1% received Stanford V scheme. Over 70% of all patients received radiotherapy (RT) with median dose of 4500 cGy (range 1000-16210). Over 94% of all patients obtained a Complete remission, however 11% relapsed. 130 patients among 361 are at this moment evaluable for late effects of chemo-radiotherapy.26 pts were treated in the period 1980-84 (25%) ; 6 pts treated 1985-89 (4,6%);21 pts treated in 1990-94 (16,1%); 24 pts treated in 1995-99 (19%) and 35 pts in the period 2000-2005 (27%). 50 pts among 130 (38,5%) present late effects related to the therapy. 24 pts (48%) present heart disease: 13 pts (40%) Valvulopathy,8 pts (25%) Ischemic heart disease, 7 pts (21%) Congestive heart failure, 4 pts (14%) Pericardic disease. Therapies of these patients were performed : In 1980-89 (11 pts), 6 pts (25%) received MOOP + RT,2 pts (8,3%) received M/A and 3 pts only RT. In 1990-99 (7 pts), 3 pts(12,5%) received ABVD +RT, 2 pts(8,3%) received MA+RT, 1 pt(4,1%) received ABVD and 1 pt(4,1%) received M/A. In 2000-05 (6 pts), 2 pts (8,3%) received ABVD+RT and 4pts(16,6%) received only ABVD. 18 pts present Endocrinological-disease, in all cases, represented by hypothyroidism; 16 pts among 18 had done Chemoteraphy and Radiotheraphy, while 2 pts received only Chemotheraphy. Besides 8 pts show both endocrinological and cardiological disease; in these cases 3 pts (37,5) had done ABVD+RT, 4 pts (50%) MOOP+RT and 1 patient (12,5%) only RT. Furthermore 26/130 (20%) developed a second neoplasm.

Conclusions
In our population 38% of patients had developed secondary late effects and we assess that about 15% of our Hodgkin's population die for a secondary late effect of therapies Although there are many variables for the development of a late effect we think that this analysis could lead to try to reduce the late toxicities of treatments.

Disclosures:
Offidani: Celgene: Honoraria; Janssen Cilag: Honoraria.