bluuebunny/crossref_metadata_2025_split huggingface dataset:
PB2044 DIAGNOSIS OF IRON DEFICIENCY ANAEMIA AND PARENTERAL IRON THERAPY: CLINICAL AUDIT IN A DISTRICT GENERAL HOSPITAL
Authors: Lovato S. , Ali H. , Dahotia B. , Bhatkal B. 
Published: June 2019

Background:Iron deficiency anaemia is the most common cause of anaemia. Parenteral iron therapy in the UK has to be administered in hospital settings as it comes with risk of allergic reactions and anaphylaxis. Clear procedures should be established in each hospital to ensure that parenteral iron therapy is prescribed according to the national guidelines ans audited regularly.Aims:The aim of this audit was to estabilish if if the diagnosis of iron deficiency was performed according to the guidelines and if patients were adequately monitored after receiving parenteral iron.Methods:Pharmacy provided the list of IV iron prescriptions issued in a period of 12 months. A clinical audit was performed to understand if patients had a documented diagnosis of iron deficiency (low haemoglobin, low ferritin or low transferrin saturation according to the local laboratory ranges); if there was a follow up blood test including the same parameters and if patients who were still iron deficient were prescribed further iron.Results:A total of 233 prescription for 227 patients were analysed. Of those 99% had a blood test previous to the iron infusion (99% had full blood count, 94% had ferritin level, 63% had transferrin saturation). Only 80% of patients had confirmed iron deficiency, in 2 % of the patients there was no iron deficiency and in 1 patient there were laboratory signs of iron overload, in the remaining 18% iron status was incomplete as transferrin saturation was not performed.Follow up was missing in 16% of the cases, in 66% of the patients was done between 2 weeks and three monts, in 20% of the cases after that. All the patients had full blood count, only two thirds had ferritin level done and less than a quarter had transferrin level done. Thirty nine patients (17% o) were found to be still iron deficient but only a fifth of them received further iron therapy. Only 10% had normal iron studies, in the remaining cases iron status was not evaluable.Summary/Conclusion:Several issues were identified that will require improvement. First of all we found that some of the prescriptions were unnecessary (2%) or controindicated (0.5%). In a fifth of the cases as iron studies were incomplete, was not possible to establish of the therapy given was appropriate. The main problem was lack of follow up or follow up with incomplete iron studies that made impossible to interpret the iron status in tre quarter of the patients, and missed iron therapy in five out of six patient with documented iron deficiency. Resolving these problem, as they are not isolated to a single department, will be a challenge. Solutions should be found to ensure that there are no inappropriate parenteral iron prescriptions and that patients are monitored adequately and given further therapy when required. Establishing an iron deficiency service to monitor patients could be one of these solutions, but it will require major institution re‐organisation.image
PB2058 THE PROGNOSTIC ROLE OF MYOCYTE‐SPECIFIC ENHANCER FACTOR 2 C (MEF2 C) IN PATIENTS WITH DIFFUSE LARGE B‐CELL LYMPHOMAS (DLBCL)
Authors: Anastasiou M. , Tsakiraki Z. , Spathis A. , Bouchla A. , Papageorgiou S. , Panayiotides I. , Pappa V. , Foukas P. 
Published: June 2019

Background:DLBCL is the most common subtype of non‐Hodgkin's lymphomas. However, the pathogenesis of DLBCL is not fully understood. Transcription factors or signaling pathways involved in normal B cell development and function might represent future therapeutic targets. Such a transcription factor is MEF2 C contributing to B cell activation and germinal center formation.Aims:This study aims at investigating the role of MEF2 C as prognostic biomarker in DLBCL.Methods82 patients with DLBCL were enrolled in our study. We assessed the expression of MEF2 C by performing immunohistochemistry (IHC) on paraffin slides of 62 tissue blocks and results were evaluated by using the H‐score semiquantitative approach, with a range from 0 to 300. Additionally, we analyzed clinical [sex, age, stage of DLBCL, performance status, extranodal sites, B symptoms, International Prognostic Index (IPI), age‐adjusted IPI, revised‐IPI, National Comprehensive Cancer Network (NCCN)‐IPI], laboratory [lactate dehydrogenase (LDH), hemoglobin (Hb), white blood cells (WBC), neutrophils, lymphocytes, monocytes, platelets and beta‐2‐microglobulin] and pathologic characteristics (CD10, BCL6, MUM‐1, Ki‐67) of patients in relation to overall (OS) and disease free survival (DFS).Results:Mean and median value of MEF2 C H‐score was 120 ± 58. We observed a statistical significant correlation with age (p= 0.021) and a tendency to correlate with LDH (p = 0.18). The expression of MEF2 C was not associated with other clinical or laboratory values. MEF2 C positivity >80% was correlated with borderline inferior OS (p = 0.083). Among patients, who survived more than 12 months after initial diagnosis, those with MEF2 C H score <120 had a significant better OS comparing with those with MEF2 C H score >120 (p = 0.009).Summary/Conclusion:High IHC expression of MEF2 C showed a negative prognostic influence in patients with OS more than 12 months after initial diagnosis. However, these results should be confirmed in larger groups of DLBCL patients and the underlying oncogenic mechanism of MEF2 C in DLBCL should be further explored.
PB2068 THE CASTLEMAN DISEASE: HISTOLOGICAL VARIANTS, POEMS‐SYNDROME AND PRODUCTIVE PLASMA CELL VASCULITIS
Authors: Mihailov A. , Bessmeltsev S. , Rugal V. , Semenova N. , Khmelnitskaya N. 
Published: June 2019

Background:The Castleman disease (CD) is a rare, little‐studied disease characterized by lymphadenopathy with follicles hyperplasia and active neoangiogenesis. Occurs in the form of two histological variants: plasma cell and hyaline‐vascular. The total vasculitis in the vessels of internal organs, previously not noted by researchers, was revealed in the analysis of 2 sectional cases of CD.Aims:To study the state of microcirculatory vessels in patients with plasma cell and hyaline‐vascular type of CD in sections of biopsied lymph nodes.MethodsSections of biopsied lymph nodes were used. It was used hematoxylin‐eosin and reaction to antibodies to CD138 to identify plasma cells. In all patients with plasma cell variant cells were painted with antibodies to HSV‐8. Vessels estimated in perinodular tissue of capsule and fat. We examined 15 patients with CD. According to histology and CD138 content, the plasma cell variant was diagnosed in 8 patients, 7 men and 1 woman aged from 40 to 70 years. In 5 patients approved POEMS syndrome by the presence of M‐protein, disorders of neuro‐muscular conduction according to the electro‐neuromyography, and other symptoms. In 7 patients was diagnosed hyaline vascular type of CD, including 5 women and 2 men aged from 30 to 60 years.Results:In 1 patient with plasma cell variant of CD revealed HSV8 reaction with intranuclear staining antibodies. Vasculitis in the form of vascular walls thickening of the microcirculatory bloodstream with a decrease or obliteration of their lumen, wall fibrosis and plasma cell infiltration was found in all 15 patients. The most pronounced changes in the form of fibrosis, complete vascular obliteration and massive perivascular infiltration CD138+ cells by type of massive colonies of hundreds of cells were found in patients with the POEMS‐ syndrome. They also noted the location of single CD138 + cells inside the intima of the sclerosal vessels. Fibroplastic vascular changes in patients with POEMS‐syndrome were weirdly shaped in the form of “mood masks”. It coincided with massive osteosclerotic changes of the vertebrae on radiographs. Massive development of fibrosis corresponds to the POEMS pathogenesis. All patients with its presence later died.Summary/Conclusion:The Castleman disease, regardless of the histological variant, includes in its morphological pattern productive plasma cell vasculitis, most pronounced in the plasma‐cell variant with POEMS‐ syndrome.
PB2102 A SAME DAY ASSAY USING CYTOCHROME C RELEASE DETERMINES SENSITIVITY TO COOPERATIVE BCL‐2 AND MCL‐1 TARGETING IN MULTIPLE MYELOMA CELL LINES AND PRIMARY SAMPLES
Authors: Grundy M. , Cull J. , Al‐Kaisi F. , Williams C. , Smith D. , Seedhouse C. 
Published: June 2019

Background:Multiple myeloma is an incurable haematological malignancy with remarkable clonal and genetic heterogeneity. Although both MCL‐1 and BCL‐2 are necessary for myeloma survival, most myelomas are dependent on MCL‐1 for survival such that BCL‐2 inhibition alone only yields significant cytotoxicty in a minority and cooperative inhibition of both proteins is required. Knowing which patients will respond can be challenging since cytotoxicty assessment of primary patient samples is significantly hampered by the lack of longevity of those cells in culture ex vivo.Aims:We aimed to study whether a short term flow cytometric assay could be used to determine cytotoxicity in myeloma cell lines and primary samples after cooperative inhibition of BCL‐2 and MCL‐1 by the BH3 mimetics (venetoclax and S63845).MethodsMyeloma cell lines and patient samples were treated with venetoclax and S63845 alone and in combinations. Sub‐toxic doses of drugs were determined for each cell line. Samples were fixed after 4 hours drug incubation thus precluding the need to keep those cells alive in culture for prolonged periods and then assayed for cytochrome c release using flow cytometry. The Bliss independence model was used to demonstrate synergy.Results:The cytochrome C release assay demonstrated that the combination of venetoclax and S63845 was synergistic as compared to controls and single agent treatment in all six cell lines tested (Combination index values 7.8‐80). All three cyclin D2 translocated cell lines were particularly sensitive to the combination and synergy was p53 independent. Furthermore, the same day assay was used on CD138‐selected primary myeloma cells also demonstrating effective cooperative targeting in patient samples.Summary/Conclusion:The attractiveness in this assay lies in its ability as a predictor of apoptotic response to chemotherapy and molecular targeting agents providing rapid results. Here, we have demonstrated for the first time in myeloma that using the cytochrome C release assay we can quickly predict apoptosis in cell lines. Importantly we are now demonstrating that this assay can also be used in primary samples. This can set the steps for an individualised assay to determine patient responses to targeted molecular therapies.
PB2145 POMALIDOMIDE AND DEXAMETHASONE IN RELAPSING POEMS SYNDROME: A FRENCH REPORT OF 5 CASES
Authors: Golfier C. , Chaubard S. , Sciortino D. , Salles G. , Viel S. , Garnier L. , Lazareth A. , Karlin L. , Jaccard A. 
Published: June 2019

Background:Significant improvements have been made in the management of POEMS (polyneuropathy, organomegaly, endocrinopathy, monoclonal gammapathy and skin changes) syndrome, but patients (pts) still experience relapses or refractoriness. Immunomodulatory drugs are effective agents in the treatment of plasma cells dyscrasias. Lenalidomide has shown interesting activity in POEMS syndrome, but no data on pomalidomide have been published so far.Aims:We report the use of pomalidomide and dexamethasone in five patients with relapsing POEMS syndrome after lenalidomide regimen.MethodsDemographics: 5 patients (3 men), median age 74 years old (range, 67–77), median of 2,6 previous lines received (range, 2–4). All patients had received lenalidomide as previous therapy.Results:Hematological overall response rate (ORR) was 3/5 (60%): all 3‐responding patients experienced complete response (CR) according to local evaluation based on IMWG criteria, leading to clinical improvement of neuropathy in all of them, endocrinopathy and peripheral edema (2 of 2 pts). Other clinical responses concerned resolution of papilledema (2 of 2 pts) and improvement of pulmonary hypertension (1 of 1 pt). Noteworthy, serum Vascular Endothelial Growth Factor (sVEGF) level normalized after only one cycle of treatment in those 3‐responding patients (figure 1). No emergent toxicity was observed. As expected, adverse events were mainly hematological but of mild intensity and easily manageable. At this time, the 3‐responding patients are alive, including 2 without relapse after 11 months of follow‐up for both of them. The 2 other patients died, one of them from rapidly progressing disease, the other from heart disease not related to POEMS.Summary/Conclusion:In conclusion, pomalidomide and dexamethasone appears to be a safe and effective option in relapsing POEMS syndrome after lenalidomide regimen, demonstrating rapid and durable responses.image
PB2151 HEPATITIS B VIRUS INFECTION MIGHT CONTRIBUTE TO MULTIPLE MYELOMA PROGRESSION THROUGH 1Q21 AMPLIFICATION
Authors: Peipei X. 
Published: June 2019

Background:Hepatitis B virus (HBV) is not only a hepatotropic virus but also a lymphotropic virus. The association between HBV and hematologic malignancies has also been described, but the correlation between HBV infection and multiple myeloma (MM) has remained controversial.Aims:This study aimed to assess the prevalence of HBV infection in patients with MM and investigate their characteristics and prognostic significance.MethodsThe clinical data of 165 patients with MM receiving at least four cycles of chemotherapy from April 2008 to February 2017 in Nanjing Drum Tower Hospital were collected. HBV markers were determined by an enzyme‐linked immunosorbent assay.Results:The rates of an acute or chronic HBV infection and resolved HBV infection in patients with MM were 12.12% and 26.06%, respectively. The gain of 1q21 was statistically significant in HBV‐positive and HBV‐negative patients (54% vs. 38.2%, P = 0.048), and the level of alanine transaminase (ALT) in HBV‐infected patients was significantly higher than that of the non‐infected group (63.29 vs. 24.66 U/L, P = 0.043). Lactate dehydrogenase, serum creatinine, and serum calcium levels were found as significant risk factors of overall survival. The progression‐free survival (PFS) of HBV‐positive patients was shorter than that of HBV‐negative patients (18.97 vs. 29.67 months P = 0.006), and HBV positive was considered an independent prognostic factor of PFS.Summary/Conclusion:HBV infection might contribute to MM progression through 1q21 amplification, and HBV markers should be closely monitored in patients with MM.
PB2154 TIME TO FIRST PLATEAU AS A PROGNOSTIC PREDICTOR IN MULTIPLE MYELOMA
Authors: Kirkizlar O. , Umit E. , Baysal M. , Bas V. , Gulsaran S. , Demirci U. , Demir A. M. 
Published: June 2019

Background:As novel treatments emerge, prognostic assessment has become the backbone of patients with multiple myeloma (MM). Depth and duration of response have been associated with survival and recently, evaluation residual disease status has been related with both progression free and overall survival.Aims:We aimed investigated the relation with time to plateau, which has been proposed by MayoClinic with survival in our patient group.MethodsData of 105 patients with MM, diagnosed and treated at our clinic between 2015 and 2018 were enrolled in a retrospective manner. All patients received bortezomib‐cyclophosphamide and dexametazone as first line therapy. Time to plateau was defined as best response date to the first line therapy.Results:Mean age was 65,86 years (28‐93). 49 patients were female (46,7%) while 56 were male (53,3). 29 patients had IgA disease while 74 were Ig G and 2 were light chain MM. 68 patients had International Scoring System (ISS) III disease (64,8%) while 27 had ISS II (25,7%) and 10 had ISS I disease (9,5%). Mean time to plateau was 6,74 months (4‐15) while mean overall survival was 44,87 months (8‐145). As all patients who were physically fit and <70 years of age have moved to autologous stem cell transplantation, we could not evaluate a duration of initial response.Patients who required less than 6 months (65 patients) to reach a plateau status had a mean survival of 47,51 months while patients requiring 6‐12 months had 41.23 months and patients who needed more than 12 months had a mean survival of 36 months.Summary/Conclusion:Despite the observation of MayoClinic, we did not observe a relation with slow responders and prolonged survival. On the contrary, we observed that patients who respond to first line therapy had a longer survival, probably related with more chemosensitive disease.
PB2174 EPIDEMIOLOGY OF MULTIPLE MYELOMA (MM) IN MOSCOW (RUSSIA)
Authors: Ptushkin V. , Vinogradova O. , Chernikov M. , Kochkareva Y. , Zherebtsova V. , Kobzev Y. , Markova E. , Shikhbabaeva D. 
Published: June 2019

Background:The incidence of MM varies greatly between countries, but since 1990 it has increased steadily. Despite improvements in the care of patients with MM, these advances have largely delivered better outcomes to patients in high‐income countries. Moscow is a big city (12.6 million inhabitants in 2018) with relatively identical protocols for the diagnosis, staging and treatment of MM.Aims:To evaluate the incidence and mortality of MM depending on age, gender and year of observation in Moscow in 2009–2019.MethodsData of 3,942 MM patients (pts) who reside in Moscow and were treated at Moscow City Hematology Center (Botkin Hospital) have been studied. It was collected from out‐ and in‐patient clinical records and state registries. The period from 2009 through 2019 was analyzed. The median follow up of patients since the diagnosis of MM was 34 (1 ‐ 423) months.Results:Among the registered 3,942 patients with MM, 1,707 were men (43%) and 2,241 women (57%). The median age at diagnosis was 65 (23–93) years. For men, it was 63 (23–93), for women ‐ 66 (29–92) years. Most of the patients were older than 65 ‐ 2047 (51.9%). Over the 10‐year period, the median age at diagnosis has increased by 3 years ‐ from 64 to 67 years.The average annual MM incidence recorded for 10 years increased by 60.52% ‐ from 1.9 to 3.05 per 100,000 population. However, such increase in the incidence was observed only for a cohort of patients older than 50 years, achieving a peak in the age range of 60 ‐ 69 years. Prevalence rate (PR) of MM has grown from 8.0 per 100,000 population in 2009 to 15.2 in 2018, mostly due to improved therapy outcomes. 2‐year overall survival was 76%, 5‐year ‐ 49%, and 10‐year ‐27%. Median overall survival of pts younger than 65 years of age at diagnosis was 79 months, 65 and older–48 months.Summary/Conclusion:Significant changes in MM epidemiology in the City of Moscow were observed. In the last 10 years, the incidence has increased mostly due to the increase of life expectancy, whereas improved MM diagnostics and treatment resulted in substantial increase in OS. In turn, this have caused MM PR increase, and this trend will most likely continue in the future.
PB2234 MUTATIONAL SIGNATURES AFFECT THE PHENOTYPIC PRESENTATION OF DISEASE SUBTYPES IN MPN PATIENTS FROM BOSNIA AND HERZEGOVINA
Authors: Islamagic E. , Kurtovic S. , Komic H. , Dizdarevic‐Rekic A. , Burekovic A. , Uzunovic A. , Kurtovic‐Kozaric A. 
Published: June 2019

Background: Philadelphia‐negative myeloproliferative neoplasms (MPNs), including PV, ET, PMF, and MPN‐U are a group of clonal myeloid disorders characterized by myeloproliferation without dysplasia. WHO 2016 revision lists the presence of driver mutations as one of several major criteria in the diagnosis of MPN patients. MPN subtypes have overlapping clinical symptoms and a common molecular basis.Aims:The aim of this study was to evaluate disease phenotypes and evolution in regards to the detected JAK2, CALR and MPL mutations in the population of MPN patients in Bosnia and Herzegovina. Also, we compared hematologic and clinical features of ET patients carrying either JAK2 or CALR mutations with JAK2 positive PV patients in order to determine the correlation of clinical features and disease evolution.Methods:A cohort of 138 patients diagnosed with MPN and treated at Clinical Center of the University of Sarajevo and Cantonal Hospital Zenica, in the period from January 2000 to June 2018 were included in this retrospective study. Analyzed patients were subcategorized according to BCR‐ABL negative MPN subtypes: ET (n = 41), PV (n = 56), PMF (n = 10), and MPN‐U (n = 31). Patients characteristics included full blood count, bone marrow characteristics, hepato/splenomegaly, overall survival as well as mutational status of JAK2, CALR, and MPL genes. Comparisons of quantitative variables between groups of patients were carried out by one‐way ANOVA. Correlation between numerical variables was tested by the Spearman's coefficient. Survival probabilities were estimated with the Kaplan‐Meier method and compared using the log‐rank test. Data were analyzed using IBM SPSS v.21.Results:In the present work, we compared hematologic and clinical features of patients with JAK2‐mutated ET with those of patients with CALR‐mutated ET and related the findings to features observed in patients with PV. Median follow‐up was 33 months (50, 45.5, 69 and 20 months for PV, ET, PMF and MPN‐U subtypes, respectively). We found that JAK2
V617F+ patients had higher values for RBC, Hb and Hct compared to CALR+ patients (p<0.05). MPL+ patients had higher values for Plt compared to JAK2
V617F+ patients (p<0.05). The mutant allele burden in JAK2
V617F+ PV and ET patients was directly correlated with hematological parameters (ρ = 0.36, ρ = 0.14, and ρ = 0.21 for Hb, RBC, and Hct, respectively) and inversely correlated with Plt count (ρ = −0.12). JAK2
V617F+ patients had worse survival compared to CALR+ and MPL+ patients, eventhough significant differences were not found (p > 0.05).Summary/Conclusion:Mutant allele burden is a determinant of the clinical phenotypic features in JAK2
V617F MPN patients. Mutational profile define clinical course and outcomes in MPN subtypes.