bluuebunny/crossref_metadata_2025_split huggingface dataset:
PB2085 ENVIRONMENTAL AND OCCUPATIONAL DETERMINANTS OF MYELODYSPLASTIC SYNDROMES: EXPOSURE, ASSOCIATION AND RISK: A CASE CONTROL STUDY FROM PAKISTAN
Authors: Anwar N. , Arshad A. , Fatima N. , Sharif S. , Zaidi M. , Shamsi T. 
Published: June 2019

Background:Myelodysplastic syndromes are heterogeneous group of haematopoietic stem cell disorders and have a variable reduction in the production of red cells, platelets, and mature granulocytes. Previous studies have emphasised the possible association of disease with environmental and occupational factors.Aims:In Pakistan and the surrounding regions, patients do not have access to prompt diagnostic and treatment facilities. Moreover, the characteristics of many patients, such as a low literacy rate, exposure to hazardous chemicals, inadequate access to milk and water, and habitual narcotics use, make them more vulnerable to diseases like MDS at an early age compared with patients in the western world. In this regard, we hypothesised to sketch a roadmap for our patients to identify risk factors in their daily routines and make them aware of related causal factors that ultimately could lead to life threatening disorders like MDS and thus minimise their disease burden. With this background and rationale, we conducted a case control study that evaluated environmental and occupational determinants as risk factors for MDS patients. To the best of our knowledge, this is the first study conducted in Pakistan in this context.MethodsThis was a case control study carried out at the National Institute of Blood Diseases and Bone Marrow Transplantation. The participants included 153 de novo MDS cases and 447 age and sex matched controls. Disease characteristics, sociodemographics and exposure to chemicals were collected through a questionnaire. The chi squared test was applied for finding associations between categorical variables, and binary logistic regression was applied to find odds ratios for significant variables.Results:Among the study participants (n = 600), there was a significant association between cases and controls regarding marital status, type of job, educational status and arsenic (p < 0.0001). There was also significant difference found in study group with language (p = 0.037) and benzene (p = 0.021). The association with residency in rural and urban areas, and milk and water source was not found significant.Summary/Conclusion:We concluded that people in developing countries such as Pakistan could be at higher risk than those in industrialized countries of getting diseases like MDS owing to the unrecognised exposure to perilous environmental and occupational factors. This study will be helpful to understand the aetiology of MDS in Pakistani population.
PB2086 LOW RISK MYELODYSPLASTIC SYNDROMES (LRMDS) RESPONSE TO ERYTHROPOIETIN MIGHT BE ENHANCED BY DIFFERENT IRON FORMULATION INFLUENCING BONE MARROW METILATION PATTERNS AND MACROPHAGES POLARIZATION
Authors: Giordano G. , Lucchesi A. , magri M. , niro G. , gasperi M. 
Published: June 2019

Background:Iron status influences dna methylation. External factors as liposomes may switc‐off bone marrow macrophages M1 polarization that is related to inflammatory status. These things are important in ineffective hemopoiesis in LRMDS.Aims:To see if sucromial iron and sodium ferrigluconate support in LRMDS shows different dna metilation patterns and macrophages polarization in bone marrow.MethodsThis study is a retrospective nonrandomized study. 45 patients with low risk refractory anemia receiving support with erythropoietin 40000 UI two times/week, b12 300 mg/day and folate 15 mg/day were divided in 3 group of 15 patients. Group A received i.v. sodium ferrigluconate 65 mg/day for 7 days/month, group B received sucrosomial iron tablets every other day, group C don’t received iron. No significant differences among median Hb level (9.5 g/dl), median age (65 yo), sex, karyotype, sEpo, ferritin, Tsat, IPSS, transfusion need, were in the three groups.Follow‐up period was 6 months.The bone marrow M1 proinflammatory macrophages (iNOShigh/CD163low/CD14 + ) and M2 antiinflammatory (iNOSlow/CD163high/CD14‐) were analyzed by cytofluorimetry and dna methylation with methylation‐specific PCR.Bone marrow aspiration, M1 and M2 count, dna methylation, Hb level, transfusion need, ferritin and tsat level, CRP were recorded bimonthly.Results:All results were recorded at time 0, 2, 4 and 6 months.M1% was 1, 0.8, 0.7, 1 in group A, 1.2, 0.9, 0.6, 0.4 in group B, 0.8, 0.8, 0.9, 1 in group C.M2% was0.4, 0.5, 0.3, 0.4 in group A, 0.4, 0.5, 0.5,0.6 in group B, 0.3, 0.3, 0.4,0.3 in group C.% of methilated cytosine was 6% in group A, 3% in group B, 5% in group C.CRP (ng/ml) was 6, 8, 10, 12 in group A, 7, 5, 3, 2 in group B, 8, 6, 5, 5 in group C.Hb concentration (g/dl) was 9, 9.8, 11.5, 11.8 in group A, 9, 10.2, 11.5, 12.5 in group B, 9.5, 10, 10.5, 10.9 in group C.Transfusion need (units) was 2 in group A, 2 in group B, 2 in group C.Summary/Conclusion:In LRMDS iron support improves erythropoietin effectiveness and reduces dna methylation. Sucrosomial iron reduces macrophages M1 polarization and CRP, improving effective hemopoiesis.image
PB2106 LOCKED NUCLEIC ACID MODIFIED OLIGONUCLEOTIDE MIMICKING MIR‐15A SUPPRESSES TUMOR CELLS PROLIFERATION IN VITRO
Authors: Li Z. , Lai Y. , Qiu L. , Hao M. 
Published: June 2019

Background:Recent studies have highlighted not only the importance of these genetic events but also epigenetic aberrations including DNA methylation, histone modifications, and non‐coding RNAs in the biology of multiple myeloma (MM). Our previous study has shown that non‐coding RNA miR‐15a inhibited the proliferation and promoted the apoptosis of MM cells. The level of miR‐15a was down‐regulated in MM cells and correlated with poor survival of myeloma patients. So, we speculated that up‐regulation the level of miR‐15a would promote MM cells death and prolong patient survival.Aims:To identify whether oligonucleotide mimicking miR‐15a (OMM‐15a) would be worked as an effective agent in the treatment of multiple myeloma and other cancer cells.MethodsOMM‐15a was artificial synthesized in two different forms, the native form and the modified form with locked nucleic acid at the both end of native OMM‐15a (LNA‐OMM‐15a). The anti‐tumor proliferation effects of OMM‐15a and their modified ones were detected in MM cell lines ARP1, OCI‐My5 and breast cancer cell line MCF7. The OMM‐15a was transfected into these cells. At the different time point after the transfection (24 hrs, 48 hrs and 72 hrs), the cell proliferation and apoptosis was detected. The quantitative real‐time PCR and western blot were performed to detect the down‐stream signaling pathway of miR‐15a.Results:Our data indicated that the native form of OMM‐15a could work as hsa‐miR‐15a, but its function was weak and short duration. It could only downregulate part of the target genes expression of hsa‐miR‐15a, PHF19 and BCL2. Only PHF19 in one (ARP1) of the 3 cell lines was downregulated in the protein level at the 24 hrs point after transfection. It could not suppress tumor cells proliferation and increase their apoptosis. However, LNA modification at the both ends of the native form OMM‐15a could increase the stability and the function of OMM‐15 and prolonged their anti‐tumor effects. After modification, VEGFA were downregulated in addition to PHF19 and BCL2. And what's more, the proteins of PHF19 and BCL2 were all downregulated in all the 3 cell lines. Moreover, the LNA‐OMM‐15a showed significant effects on suppression of the tumor cells proliferation and on promotion of cells apoptosis.Summary/Conclusion:Treatment with LNA‐OMM‐15a significantly inhibited the proliferation of tumor cells. Cell apoptosis were up‐regulated notably in MM and other tumor cells. This preclinical study indicates that the LNA‐OMM‐15a would be work as a potential effective agent for tumor treatment.
PB2141 FEATURES OF THE DIRECT ANTIGLOBULIN TEST IN PATIENTS WITH MULTIPLE MYELOMA
Authors: Poponina E. , Butina E. , Yovdiy A. , Zaitseva G. , Vaneeva E. , Paramonov I. 
Published: June 2019

Background:The direct antiglobulin test (DAT) is used to detect autoantibodies that are fixed on the surface of red blood cells. A differentiated DAT allows to estimate the amount of absorbed immunoglobulins, describe their class and subclass, and detect the components of the complement on the membrane of red blood cells. This information helps to predict the risk of hemolysis and suggest the cause of anemia in a particular patient.Aims:To study the frequency and features of positive DAT in patients with multiple myeloma (MM).MethodsThe results of differentiated DAT were analyzed in 80 patients first hospitalized at the Institute clinic in 2018–2019 with the diagnosis MM. DAT was performed by gel method using anti‐IgG/C3d, DC‐Screening I and DAT IgG1/IgG3 cards (BioRad, USA). The frequency of positive DAT in patients was compared with the same in 200 healthy residents of the region–donors of blood components.Results:All blood donors were DAT‐negative. Autoantibodies to red blood cells were detected in 27.5% (22) of patients with MM (p < 0.05).The intensity of the reaction (+) was observed in 50.0% (11) of patients with positive DAT, (++)–in 50.0% (11). DAT (++ + ), (++ + +) was not revealed. In the 100% of cases immunoglobulins G subclasses 2,4 were fixed on the surface of red blood cells, associated with a low risk of immune hemolysis. None of the patients was positive due to immunoglobulins classes A, M and complement components, which could contribute to the development of hemolytic complications. No clinical and laboratory signs of hemolysis were observed in the patients with positive DAT.Positive DAT was more frequently found in the group of patients with MM older than 60 years (48.0%), whereas in the group of patients younger than 60 years it was 18.2% (p <0.05).When observing patients with MM with positive DAT, it was noted that in one third of patients receiving chemotherapy, the result of DAT becomes negative within 5 months.Autoantibodies can interact with test and donors red blood cells, being detected in an indirect antiglobulin test (IAT). Positive IAT was in 9.1% of patients with positive DAT and in 3.4% ‐ with negative. These patients had difficulties in donor's selection due to non‐specific agglutination.Summary/Conclusion:Even though positive DAT is often found in patients with MM, not in every case it should be regarded as a sign of autoimmune hemolysis. To correctly assess the risk of hemolysis, physicians should analyze other laboratory and clinical data. Positive DAT may be correlated with the difficulties of selection of the donor for such patient.
PB2143 HEPATITIS B VIRUS INFECTION MIGHT CONTRIBUTE TO MULTIPLE MYELOMA PROGRESSION THROUGH 1Q21 AMPLIFICATION
Authors: Xu P. , Guo D. 
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.
PB2156 RISK FACTORS ASSOCIATED WITH EARLY MORTALITY IN PATIENTS WITH MULTIPLE MYELOMA
Authors: Novikova A. , Nakastoev I. , Balzhanova Y. , Ryzhko V. , Grachev A. , Danilina A. , Kanaeva M. , Klyasova G. , Gribanova E. 
Published: June 2019

Background:Early mortality (EM) in multiple myeloma (MM) ranges from 4% to 25% mostly depending on the patients included and on treatment options. EM tends to be lower in clinical trials including younger, transplant‐eligible patients or in bortezomib‐ and lenalidomide‐based regimens in comparison with elderly patients and conventional chemotherapy treatment.Aims:To estimate risk factors associated with EM in patients with newly diagnosed MM.MethodsPatients with newly diagnosed MM were included into the study (from Jan 2013 to Feb 2019). EM was defined if it occurred within 1 year of entry into the study. Adverse cytogenetic abnormalities were specified as gain(1q), t(4;14), t(14;16), t(14;20) or del(17p).Results:A total of 174 patients with newly diagnosed MM (82 male, 92 female; median age 61 years) were involved in the study. Follow‐up period was 1‐71.4 months (median 8 months). The majority of patients developed an advanced stage of disease (Duriе‐Salmon stage 3–141 (81.1%), ISS stage 3–99 (56.9%)). All patients received chemotherapy regimens containing proteasome inhibitors as first‐line therapy and immunomodulatory drugs, intensive and conventional chemotherapy regimens as second‐ or next‐line therapy. During follow‐up period fatal outcome was observed in 45 (25.9%) of 174 patients, of them 16 (9.2%) patients with EM. Median early mortality was 4.7 months. The age of patients with EM and patients survived > 1 year was comparable (median age 64.5 vs. 61, respectively). A larger proportion of patients with EM had Durie‐Salmon stage 3 (93.8% vs 79.7%), ISS stage 3 (75.0% vs 55.1%). Fish in situ hybridization analysis was conducted in 126 (72.4%) patients, adverse cytogenetic abnormalities were present in 4/8 (50.0%) patients with EM and 33/118 (27.9%) patients survived >1 year. Risk factors assotiated with EM were ECOG performance status ≥ 3 score (87.5% vs 40.5%, p = 0.0003), C‐reactive protein level > 10 mg/L (62.5% vs 26.6%, p = 0.007), high lactic acid dehydrogenase activity (81.3% vs 46.2%, p = 0.008), platelet count < 150 × 109/L (43.8% vs 18.9%, p = 0.047) (tab.). For the 16 patients with EM, 11 (68.8%) of deaths were related to MM progression, 4 (25.0%) were due to infections and 1 (6.2%) ‐ heart failure.Summary/Conclusion:EM in patients with newly diagnosed MM was 9.2%. Risk factors associated with EM were poor performance status, elevated serum LDH activity, low platelet count, high serum C‐reactive protein.image
PB2160 REAL LIFE EXPERIENCE OF TREATMENT WITH POMALIDOMIDE, CYCLOPHOSPHAMIDE AND DEXAMETHASONE COMBINATION IN ADULT PATIENTS WITH RELAPSED AND REFRACTORY MULTIPLE MYELOMA
Authors: Alarcón‐Payer C. , Sánchez M. E. Clavero , Collado C. García , Chacón M. Jurado , Morales A. Jiménez 
Published: June 2019

Background:Multiple myeloma is a plasma cell malignancy that accounts for 1% of all cancers. Despite available therapies, the disease remains uniformly fatal, and patients who have received prior lenalidomide and bortezomib have a median overall survival of 9 months. Pomalidomide and low‐dose dexamethasone (PomDex) is standard treatment of lenalidomide refractory myeloma patients who have received >2 prior therapies. Combination therapy is often used in clinical practice in an attempt to overcome drug/clone resistance.Aims:Evaluate in daily clinical practice the effectiveness and safety of the combination pomalidomide, cyclophosphamide and dexamethasone (PomCyDex) in adult patients with relapsed and refractory multiple myeloma (RRMM).MethodsFour‐year prospective observational study on 33 cases of RRMM. To measure the health outcomes obtained with the PomCyDex combination in a third level hospital we used the median progression free survival (PFS) as the main variable to assess if the combination is effective. Age, number of previous treatment lines and most frequent adverse reactions were also measured.Results:33 RRMM cases were analyzed, (57.6%: women; 42.4%: men). The mean age was 68 years. The health outcomes measured in our clinical practice were as follows: 39.4% of the patients were treated with PomCyDex in the 3rd line, 15.1% in the 4th line, 24.3% in the 5th line, 18.2% in the 6th line and 3% in the 7th line. The mean number of PomCyDex cycles received was 9. The median PFS was 5.5 months. PomCydex combination was shown to improve PFS by an additional 1.5 months compared to PomDex‐only patients receiving a 4 month PFS (MM‐003). The most frequent adverse reactions observed were neutropenia (38%), anaemia (11%) and thrombocytopenia (5%).Summary/Conclusion:Treatment with PomCyDex is an effective combination in the treatment of adult patients with RRMM. Also, PomCyDex combination is well tolerated in most patients and is therefore considered a safe treatment.
PB2162 INCIDENCE & SEVERITY OF BORTEZOMIB‐INDUCED PERIPHERAL NEUROPATHY WITH THE USE OF GENERIC BORTEZOMIB IN MONOCLONAL GAMMOPATHIES: A PROSPECTIVE STUDY FROM INDIA
Authors: Nath U. K. , Vaniyath S. , Chetia R. , Chattopadhyay D. 
Published: June 2019

Background:The proteasome inhibitor Bortezomib is one of the most effective frontline drugs in the therapeutic armamentarium against monoclonal gammopathies. However, drug‐induced peripheral neuropathy is the major dose‐limiting toxicity and adversely affects quality of life. Generic preparations of bortezomib are mainstay of therapy in resource‐poor countries due to significantly higher cost of original brand of bortezomib.Aims:The present study aims to analyze the incidence & severity of bortezomib‐induced peripheral neuropathy (BIPN) in patients of monoclonal gammopathies receiving generic bortezomib in a resource‐poor setting.MethodsThis non‐randomized, prospective study enrolled total 73 bortezomib‐naïve patients of monoclonal gammopathies between July 2016 & February 2019. Both newly diagnosed & relapsed patients of symptomatic multiple myeloma (MM), Waldenstrom macroglobulinemia (WM) & primary amyloidosis, who had no baseline evidence of peripheral neuropathy were included. Patients having disease‐related neuropathy & patients who had earlier received thalidomide or other neurotoxic drugs were excluded. All study patients received one of the generic bortezomib brands available in India. Bortezomib was initially administered at 1.3 mg/m2 dose, by subcutaneous injection, on days 1,8,15,22 of each 28 days’ cycle. Patients were clinically evaluated for BIPN before each cycle, & at onset of BIPN symptoms. Bortezomib dose was modified according to grade of BIPN (Table 1). Bortezomib was discontinued in grade 3‐4 neuropathy, & restarted after BIPN symptoms improved to < grade 3.Results:Median patient age was 58 years (32‐76 years). Majority (62/73 patients, 85%) had MM, eight patients had WM & three patients had Primary Amyloidosis. Twenty‐seven patients in the study (37%) developed BIPN during treatment. Severity of BIPN in study is shown in Table 2. BIPN symptoms were reversible in 90% patients after discontinuation of bortezomib. Median follow up was 7 months (2‐18 months).imageSummary/Conclusion:In our study, approximately one‐third of patients with monoclonal gammopathies treated with subcutaneously administered generic bortezomib developed bortezomib‐induced peripheral neuropathy. The incidence of severe (grade 3‐4) BIPN was about 12%, leading to temporary/permanent discontinuation of bortezomib and also interfering with quality of life.image
PB2175 LONG TERM FOLLOW‐UP OF MAINTENANCE THERAPY WITH INTEREFRON ALPHA AFTER AUTOLOGOUS HEMATOPOIETIC STEM CELL TRANSPLANT IN MULTIPLE MYELOMA PATIENTS–SINGLE CENTER EXPERIENCE
Authors: Batinic J. , Bašić‐Kinda S. , Pulanić D. , Ostojić A. , Dreta B. , Hude I. , Sertić D. , Seiwerth R. Serventi , Duraković N. , Rončević P. , Bojanić I. , Gjadrov‐Kuveždić K. , Dubravčić K. , Batinić D. , Ilić I. , Aurer I. , Nemet D. 
Published: June 2019

Background:Maintenance therapy after autologous hematopoietic stem cell transplantation (AHSCT) in multiple myeloma (MM) patients was a matter of debate until recently, when lenalidomide in this setting proved to increase overall survival (OS). Before lenalidomide interferon alpha (IFN) was standard maintenance therapy.Aims:The aim of this analysis was to determine the impact of maintenance therapy after AHSCT on progression free survival (PFS) and OS in MM patients treated at our institution between 1993 and 2014.MethodsWe performed a retrospective analysis of outcomes of MM patients autografted at our institution between 1993 and 2014. We identified 274 pts. who had PFS at least 6 months posttransplant; median age was 57, range 28‐71, 48% were male. 124 of them received tandem and 150 single AHSCT. Median follow‐up was 62 mo. Posttransplant 200 patients received IFN, 44 thalidomide and 30 no maintenance according to physicians’ choice.Results:Patients receiving IFN had longer 5‐year PFS compared to patients receiving thalidomide or no maintenance (52% vs. 34% vs. 31%, respectively, p < 0.001). OS was best in the IFN group, intermediate in the thalidomide and worst in the no maintenance group (67% vs. 59% vs. 32%, respectively, p < 0.001). The difference was limited to patients receiving tandem transplants. In this group 5‐year PFS was 61% vs. 35% vs 0% (p < 0.001) and OS 85% vs. 67% vs. 65% (p = 0.003) in the IFN, thalidomide and no maintenance group respectively. In patients that received a single transplant 5‐year PFS was 43% vs. 33% vs 36% (p = 0.157) and 5‐year OS 70% vs. 75% vs. 54% (p = 0.06) in the IFN, thalidomide and no maintenance group respectively.Summary/Conclusion:Our results indicate that maintenance therapy has beneficial effects on OS and PFS in MM patients treated with tandem, but not single AHSCT. IFN is superior in this setting to thalidomide and could be considered as a treatment option when lenalidomide is not available.