bluuebunny/crossref_metadata_2025_split huggingface dataset:
PB1649 EXOSOMES‐MEDIATED DELIVERY OF RNA OLIGOS DIRECTED TO CHE‐1/AATF IMPAIRS BCP‐ALL VITALITY
Authors: Caforio M. , Sorino C. , Bertaina V. , Pitisci A. , Battafarano G. , Del Fattore A. , Fanciulli M. , Folgiero V. , Locatelli F. 
Published: June 2019

Background:Precursor B cell acute lymphoblastic leukemia (BCP‐ALL) is the most common childhood malignancy and represents the leading cause of cancer‐related death in children and young adults. BCP‐ALL arises from a monoclonal or oligoclonal expansion of malignant B cell precursors in the bone marrow and despite the overall progress in treatment relapse occurs across the whole spectrum of all subtypes with an overall survival of 30%. We recently found that Che‐1/AATF, an important RNA polymerase II binding protein involved in the regulation of gene transcription with anti‐apoptotic activity in different tumour contests, exerts a pivotal role in BCP‐ALL. Che‐1 is highly expressed in a cohort of BCP‐ALL patients at the onset of disease and at time of relapse, irrespective of genetic heterogeneity, but were barely detectable when patients obtained leukemia remission. Notably, Che‐1 depletion strongly affected growth of BCP‐ALL cells and sensitized to Adriamycin.Aims:With the aim to therapeutically inhibit Che‐1 expression, overcoming the difficulty of the nuclear localization, and to find a technical approach available in in vivo models we focused on exosome‐mediated delivery of RNA oligos.Methods:To test this hypothesis, peripheral blood obtained from healthy donors was used for monocytes isolation and differentiation to immature dendritic cells. Supernatants were harvested and submitted to exosomes extraction procedure. Vesicles were electroporated with FITC‐conjugated oligos to set up experimental conditions. We observed high oligos loading and a 100% efficiency of oligo delivery in BCP‐ALL cell lines and in primary blast cells upon cellular co‐culture. In the same experimental conditions, we tested the efficacy of a panel of FITC‐conjugate oligo targeting Che‐1.Results:The exosome‐mediated delivery of combination of two oligos resulted in downregulation of Che‐1 expression in BCP‐ALL cell lines. The obtained result produced also an increase in PARP cleavage and an higher amount of cells in subG0‐1 phase.Summary/Conclusion:Since part of this procedure is an already approved GMP‐grade procedure, we will test the cooperation between exosome‐mediated Che‐1 downregulation and the current therapeutic treatments with the aim to develop a new applicable clinical approach, particularly in BCP‐ALL relapsed patients.
PB1731 ELEVATED FETAL HEMOGLOBIN (HBF) IN ELDERLY AML PATIENTS RECEIVING HYPOMETHYLATING AGENTS: ENHANCEMENT OF HBF INDUCTION BY RETINOIC ACID?
Authors: Stomper J. , Bissé E. , Lübbert M. 
Published: June 2019

Background:We recently reported elevation of fetal hemoglobin (HbF) as a potential predictor of outcome in elderly AML/MDS patients treated with DNA‐hypomethylating agents (HMA). HbF elevation prior to decitabine (DAC) treatment (Lübbert et al., Br. J. Haematol. 2017; 176:609‐617) as well as HbF induction following 2 courses of DAC treatment (Stomper et al., Haematologica 2019; 104:59‐69) were associated with superior outcome of AML/MDS patients. Interestingly, HbF elevation was shown to be associated with cytogenetic remissions and to be reversed at relapse, suggesting that HbF is preferentially induced in non‐clonal erythroid cells during HMA therapy.Preclinical work suggests that epigenetically active agents such histone deacetylase inhibitors (HDACi) can be combined with retinoic acid to induce HbF.Aims:We now investigated the effect of the add‐on drugs all‐trans retinoic acid (ATRA) and valproic acid (VPA, an HDACi) on HbF induction during DAC treatment in AML patients.Methods:The DECIDER trial addresses the effects of the add‐on of ATRA or VPA to DAC (Grishina et al., BMC Cancer 2015; 15:430). We serially studied HbF levels in 16 AML patients ≥60 years old that received >2 cycles of treatment within the DECIDER trial. Four patients received only DAC, 5 patients DAC+VPA, 5 patients DAC+ATRA, and 2 patients DAC+VPA+ATRA. HbF levels were measured in peripheral blood erythrocytes by HPLC before treatment and sequentially, i.e. after the end of each treatment course. HbF >1.0% was considered induced.Results:In this albeit small cohort, continued treatment appeared to result in variations in maximally attained levels of HbF depending on the type of drug add‐on. As to VPA, the median peak HbF level attained was 1.5% (range, 0.4 ‐ 5.0%) in 9 patients not having received VPA compared to 1.0% (range, 0.2 ‐ 4.8%) in 7 patients having received VPA. The median peak HbF level in the absence of ATRA (9 patients) was 0.8% (range, 0.2 ‐ 2.8%) compared to 2.1% (range, 0.3 ‐ 5.0 %) in 7 patients having received ATRA.Summary/Conclusion:Given that the add‐on of ATRA (but not VPA) to DAC resulted in superior outcome (Lübbert et al., ASH 2016), these preliminary results suggesting a higher induction of HbF in the presence of ATRA warrant prospective, serial HbF determinations in a planned randomized validation trial. Also, RNA‐sequencing studies in AML cell lines treated with DAC ‐/+ ATRA are addressing de‐repression of the gamma‐globin locus in vitro.
PB1848 CAN VON WILLEBRAND ANTIGEN LEVEL AT THE INITIAL PRESENTATION BE ABLE TO PREDICT THE INHIBITOR DEVELOPMENT IN PATIENTS WITH SEVERE HEMOPHILIA A?
Authors: Aytac S. , Gumruk F. , çetin M. 
Published: June 2019

Background:There is a large heterogeneity in bleeding events and arthropaty among patients with severe Hemophilia A which is multifactorial. Mostly FVIII gene mutations seems to influence phenotype however underlying prothrombotic risk factors and FVIII half life may both have an affect on the heterogeneity.VWF is the specific carrier of factor VIII in plasma and protecs it from proteolytic degradation,prolonging its half life in circulation and efficiently localizing it at the site of vasculary injuiry.Aims:Here, we want to evaluate von Willebrand antigen levels of the children with severe Hemophilia A at the initial diagnose and want to figure out whether low initial von Willebrand antigen (VWF:Ag) levels may asssociated with a frequent bleeding phenotype or not, retrospectively.Methods:We retrospectively evaluate charts of 40 children with severe hemophilia A who was diagnosed in between 1997 and 2017 at the Hacettepe University, Department of Pediatric Hematology. All of these patients were receiving prophylaxis and among those 40 patients only 6 had a history of inhibitor in which 2 of them still persist.Results:Mean VWF:Ag levels were found to be 114 ± 40 (32‐200)IU/dL. Ten out of 40 children VWF:Ag levels was found to be under 100IU/dL and from those 5 out of ten were found to be under 80IU/dL. Interestingly none of them were have the blood group ’O’. Initial bleeding age were found to be lower (median 6 months)in patients with low VWF:Ag (<100IU/dL) than that of the patients with high VWF:Ag (≥100IU/dL)(median 18 months)(p = 0.05).2/10 had a history of inhibitor (1 low titer 1 high titer) development and 7/10 had a target joint which requires radiosyneviectomy during the follow up period.On the other hand 4 out of 30 patients with VWF:Ag>100IU/dL had a history of inhibitor development (4 high titre inhibitor: 2 was still found to be positive) and 5/30 had a target joint.Summary/Conclusion:Despite we do not have the half lifes of FVIII, a significant shorter half life in patients with a low VWF:Ag level was previosly reported. Although there is no follow up of VWF:Ag levels in this small group of patients with a frequent bleeders initial VWF:Ag levels may give some clues about the clinical outcome.
PB1849 WHEN DO WE HAVE TO SUSPECT AND DIAGNOSE VON WILLEBRAND DISEASE?
Authors: Hyun S.Y. , Lee K.S. 
Published: June 2019

Background:Although von Willebrand disease (vWD) is the most common hereditary coagulation disorder, most of patients do not pay attention to their daily lives. While it is easy to treat already diagnosed vWD patients, it is also a characteristic of the disease that it is not easy to suspect and diagnose. The patient does not tell the doctor easy bruise as a major symptom because he (or she) does not know that this may have been caused by coagulation disease. It is very important to ask the patient whether he suffers from ’easy bruise or intractable nosebleed?’, ’ever suffered from poor stop‐bleeding on the injection site?’ or ’a family history of bleeding disorders?’ to determine the pressure time (10 minutes or more) to stop the injection site bleeding in cases of invasive procedure such as vaccination, blood collection or injection even when the patient is diagnosed and treated with other diseases. Menorrhagia or hypermenorrhea, delivery history and family history of coagulation disorder is hard to get medical history without specially asking. The reason why we are difficult to suspect and diagnose vWD: Many think easy bruise is not a disease. No one considered a repeat intractable nosebleed after stop as a result of basically coagulation defect. It seems to accept menorrhagia or hypermenorrhea as a mother's similarity and to solve only by gynecological treatment. Most doctors fail to treat iron deficient anemia because they do not pay attention for etiology. Do not recognize repeat test may be necessary because exercise and stress will make false positive result of vWF.Aims:Objective of this study was to examine the icidence and clinical features of VWD among the patients with easy bruising in the setting of primary care clinic.Methods:The screening test and the primary specific test for vWD (FVIIIc, vWF:RiCoF and vWF:Ag) and iron deficiency anemia (IDA) were done in 182 patients with bleeding symptoms (menorrhagia, easy bruising, etc.) among the patients who visited one private physician's clinic (Han's Clinic) for 4.5 years.Results:Twenty‐one patients were confirmed as vWD (vWF:RCo or vWF:Ag value was less than 30 or vWF:RCo/vWF:Ag < 0.6) and 23 had vWF values less than 50. All except two were female. Median age was 34.7 (13‐71) years. Six of 21 patients had a family history. Most of them had iron‐deficiency anemia of moderate to severe. The main symptom was easy bruise in 16, anemia in 10, menorrhagia in 7, hypermenorrhea in 5, easy epistaxis in 2 and dizziness in 1. Iron deficiency anemia was confirmed in 8 of 21 patients. Four patients received prophylactic therapy with Minirin® effectively and 1 had treated with Immunate® for tooth extraction and 50 days’ menstruation. The menstrual period lasting for one month was reduced to normal with DDAVP inhalation and vWF infusion could stop bleeding soon after tooth extraction.Summary/Conclusion:Because accidents or emergency surgery can happen in life time to anyone, early suspicion and diagnosis will save life and reduce sequelae.
PB1859 PROSPECTIVE COHORT STUDY OF KOREAN PATIENTS WITH BONE MARROW DISORDERS WITHOUT LARGE PNH CLONE TO DEFINE FACTORS ASSOCIATED WITH PNH CLONE EXPANSION
Authors: Koh Y. , Yoon S.‐S. , Lee J.W. , Jang J.H. , Lee J.‐H. , Kim J.S. , Choi S.E. , Kim S.‐H. 
Published: June 2019

Background:Factors associated with PNH clone evolution is not well described in the Asian population.Aims:In this prospective cohort study, we recruited Korean patients with bone marrow disorder to define factors associated with an increase in PNH clone size.Methods:We included patients with aplastic anemia (AA) or myelodysplastic syndrome (MDS) if PNH clone is not absent at the time of screening. We also included patients who have small PNH clones (<10%) regardless of bone marrow pathology except for hematologic malignancies. Patients should be free of complement inhibitor treatment for at least 8 weeks before study enrollment. PNH clone size testing was performed using high‐resolution flow cytometry and FLARE.Results:We enrolled 227 patients (Male:Female 121:106, mean age 53 years) from 6 centers in Korea. PNH clone was ≥ 1% in 28 patients, 0Table1 Characteristics of 5 patients who experienced more than 10% of PNH clone expansionSummary/Conclusion:We constructed a prospective cohort of Korean patients with AA, MDS or small PNH clones. PNH clone distribution had a distinctive pattern according to underlying bone marrow pathology. We expect to construct a precise model for PNH clone expansion using this cohort.image
PB1957 EVALUATION OF HEMATOLOGICAL AND NONHEMATOLOGICAL COMPLICATIONS OF IMATINIB MESILATE (IM) IN PATIENTS WITH PHILADELPHIA POSITIVE CHRONIC MYELOGENOUS LEUKEMIA (PH+ CML)
Authors: Ter‐Grigoryan A. , Melkikyan N. , Danelyan S. 
Published: June 2019

Background:Chronic myelogenous leukemia (CML) is caused by the BCR‐ABL tyrosine kinase, the product of Philadelphia chromosome. Imatinib mesylate (IM) is a selective inhibitor of this kinase.Aims:The objective of this study was to determine the hematological and non‐hematological complications of IM in patient with CML in Armenian population.Methods:The object of the study were patients of the Hematology Center of the Ministry of Health of the Republic of Armenia, registered from 2000 to 2017. During this period 377 patients with a diagnosis of Ph+ CML were observed. Total of 326 (86%) patients treated with IM were involved in research (45.4% male and 54.6% female, who were at the age of 7‐81 years). The 282 patients (86.5%) were in chronic phase, 44 patients (13.5%) ‐ in phase of acceleration and blast crisis. The doses of IM were 400 mg daily for the chronic phase and 600‐800 mg daily for the accelerated and blast phase of disease. The patients were thoroughly monitored for both hematological and non‐hematological complications, in some cases temporary dose adjustment was necessary.Results:213 patients experienced various side effects which, in decreasing order of frequency were: peripheral edema, bone pains, joint pains, allergic reactions, muscle cramps, nausea, vomiting, hepatic enzyme elevation, gastric pain and headaches as non‐hematologic complications (table 1) and leucopenia, thrombocytopenia and anemia as hematological complications (table 2).Three patients developed grade IV complications in form of toxic hepatitis, anasarca and allergic reaction, which required treatment discontinuation.Cytopenias developed in cases of 48 patients, and CHR/complete hematological response/ within the first 4 months from the start of therapy was observed in 65.3% of their cases. At the same time, in the group of patients who did not have these complications, CHR was achieved in 84% of cases (p = 0.0207).It is noteworthy that in case of patients with cytopenias, CCR/complete cytogenetic response/ was achieved in 15.3% of cases, whereas in case of patients without these complications‐ in 32.4% of cases (p = 0.0754). Thus, hematological complications in the form of cytopenias, which require a temporary cessation of treatment, reduce the likelihood of CHR and CCR.Such statistics show that hematological complications, quite possibly, were originally due to patients belonging to a higher prognostic group. And the group of patients, who in the first 4 months did not reach the CHR, requires a broader cytogenetic examination according to the karyotype and, if necessary, sequencing.Summary/Conclusion:Imatinib mesylate is a well‐tolerated drug with some adverse events that rarely require treatment discontinuation.image
PB2000 OUTCOME OF PEDIATRIC NODULAR LYMPHOCYTE PREDOMINANT HODGKIN LYMPHOMA, IS ABVD THE BEST REGIMEN? 10 YEARS SINGLE CENTER EXPERIENCE, REPORT FROM CHILDREN CANCER HOSPITAL, EGYPT.
Authors: Madney Y. , abdallha A. , Ahmed S. , romeih M. , fikry S. , zaghloul M. , taha H. , Mohammed E. , attia I. 
Published: June 2019

Background:Nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) is an uncommon subtype of Hodgkin lymphoma (HL) in children and accounts for 5–10% of all pediatric HL.Aims:The aim of the study to analyze the clinical characteristics and treatment outcome of Pediatric NLPHL.Methods:Retrospective study including all newly diagnosed patients less than 18 years old with NLPHL and treated in children cancer hospital Egypt CCHE between 2007 and 2017.Results:Among 43 pediatric NLPHL patients, 29 had early stage (18 with stage I, 11 with stage II). Fourteen patients had advanced stage (7 with stage III & 7 with stage IV). Eleven patients had a mediastinal disease, 8 patients had splenic involvement, 2 patient had bulky disease and 10 patient had B symptoms at diagnosis.28 Patients with Early‐stage disease treatment; surgery and observation 6 patients, Chemotherapy 6 patients and Combined modality 17 patients. Relapse was seen in 7(25%) patients, 1 observation arm, 3 from chemotherapy arm (ABVD) and 3 from the combined arm (ABVD+IFRTH). 14 advanced stage patients received treatment; Chemotherapy (ABVD) 6 patients, Combined (ABVD+IFRTH) 8 patients, Relapse in 7 (50%) patients (all stage 4 disease), 6 from chemotherapy arm and 1 from the combined arm. 2 patients died (stage IV) from progressive disease and sepsis. B symptoms, mediastinal and splenic involvement had a significant impact on DFS on univariate analysis while combined treatment modality (Chemotherapy and Radiotherapy) had an impact on the outcome of both univariate and multivariate analysis.5 Years DFS, OS for whole group was 64% and 94% respectively, while 5y DFS for early stage 83% and advanced stage 45% (p‐value = .01) and 5 Years OS for early stage was 100% and advanced stage 87 % (p‐value = .08).Summary/Conclusion:Early stage NLPHL had a better outcome but unexpected higher relapse in chemotherapy treatment arm raising a question about the role of radiotherapy while advanced stage disease had poor outcome rising a question of what should be the best chemotherapy regimen for pediatric NLPHL patients.
PB2144 PRESCRIPTION PATTERNS AND OUTCOMES OF FIRST‐LINE THERAPY FOR NON‐TRANSPLANT ELIGIBLE MULTIPLE MYELOMA REAL‐LIFE PATIENTS ACCORDING TO AGE: A RETROSPECTIVE ANALYSIS OF THE 2012‐2016 PERIOD
Authors: Cejalvo M. J. , Sureda A. , González E. , Vázquez‐Álvarez J. , García R. , Ramírez Á. , Pérez‐Persona E. , Abella E. , Garzón S. , García A. , Jarque I. , González M. S. , Sampol A. , Motlló C. , Martí J. M. , Alcalá M. , Duro R. , González Y. , Sastre J. L. , Sarrà J. , Lostaunau G. , López R. , de la Rubia J. 
Published: June 2019

Background:Multiple myeloma (MM) affects elderly individuals with two‐thirds of patients aged >65 years at diagnosis, 35% ≥75 and 10% ≥80. In general, routine clinical practice is based on the results of large, multicenter, randomized clinical trials. However, despite efforts from cooperative groups, patients enrolled in trials are generally younger and presumably healthier than the typical older patient with MMAims:To describe prescription patterns for first‐line treatment of non‐transplant eligible MM patients in the setting of real‐life practice and to analyze treatment outcome according to patients’ ageMethodsRetrospective analysis of newly diagnosed MM patients not eligible for transplantation, who started anti‐myeloma treatment between 2012‐2016 in 20 Spanish hospitals. Variables collected included patients’ characteristics at diagnosis (ECOG, laboratory parameters, ISS, and cytogenetics/fluorescent in situ hybridization), characteristics of first‐line treatment, overall survival (OS), progression‐free survival (PFS), and overall response rate (ORR), defined as partial response or betterResults:The retrospective cohort included 421 patients with a median age of 76 years (41‐90); 203 (49%), 106 (26%), and 104 (25%) were ≤75, 76‐80, and >80 years old, respectively; 28 (12%) had ECOG >2. ISS staging was I, II, III in 57 (18%), 93 (30%), and 160 (52%) patients, respectively; 73 (25%) patients had high‐risk cytogenetics. The most frequently prescribed regimen was VMP (208 patients), followed by other bortezomib‐based regimens (130 patients) (Table 1). Overall, median treatment duration was 6 months (95%CI 5‐7) and the ORR was 74% (for patients ≤75, 75‐80, and >80 years old: 76%, 80%, and 62%; P = 0.025). Overall, 188 (45%) patients required a dose adjustment and 225 (81%) started second‐line treatment. Median OS and PFS were 32 (95% CI 29‐37) and 15 months (95% CI 14‐17), respectively. OS and PFS of patients ≤75, 75‐80, and >80 years old were 44 and 16 months, 28 and 17 months, and 23 and 12 months (P < 0.01 for age‐group differences in both OS and PFS).Summary/Conclusion:In real‐life practice, there is high variability in treatment regimens, being bortezomib‐based the most frequently prescribed regimens in the study period. Besides the clinical characteristics of MM patients, age influenced survival in our cohort of real‐life patients, suggesting that treatment choice for elderly patients should be based on a specific pre‐treatment assessment of risks and benefits.image
PB2172 THE EFFECTS OF CURCUMIN ADDITION ON REMISSION STATUS OF MULTIPLE MYELOMA PATIENTS
Authors: Santosa D. , Suharti C. , Riwanto I. , Dharmana E. , Pangarsa E. Adi , Setiawan B. , Suyono S. , Tobing M. Lumban 
Published: June 2019

Background:The standard treatment for multiple myeloma (MM) which ineligible transplant is melphalan prednisone (MP). Curcumin has anti‐inflamatory, anti angiogenesis, decrease proliferation and delay progression of monoclonal gammopathy undetermined significant or smoldering myeloma. There is no study of curcumin in MM patientsAims:To evaluate the effect of curcumin addition to remission status at MM patient with regiment MPMethodsThis experimental study was involved 35 patients which randomly into treatment (n = 17) and control (n = 16). The treatment group was given melphalan 4 mg/m2, prednisone 40 mg/m2 (MP) for 7 days and curcumin 8 gram daily for 28 days. The control group was given MP and placebo. Remision status was evaluated after 4 cycles treatment. The difference between two groups was analysed by Mann‐Whitney U‐Test. Trend analysis was evealuated by Friedman. Remission status was evaluated by Chi‐square. Multivariate analysis was evaluated by multiple logistic regression.Results:There was a significant decrease of NF‐KB, VEGF, TNF‐α, LDH levels in the treatment group compared with control. There was a decreasing trend of IL‐6 levels in the treatment group significantly. There was significant difference of remission status beetween the treatment and control group [(75 vs 33.3), X2 = 6.89,df = 1, p = 0.009]. There was significant correlation between TNF‐α levles and remission status [OR = 1.35; (95% CI = 1.03‐1.7.6), p = 0.03].Summary/Conclusion:The curcumin addition on MM patient with MP regiment improved the remision status through decreased of TNF‐α levels.