bluuebunny/crossref_metadata_2025_split huggingface dataset:
PB2176 DIAGNOSIS AND MANAGEMENT OF SYSTEMIC AL AMYLOIDOSIS IN REAL WORLD
Authors: Sirvent M. , Ondarra L. , Segues N. , Sarasqueta C. , Alkorta A. , Hernandez M. , Caminos N. , Perez E. , Romero P. , Zeberio I. , Aranbarri A. , Otero I. , Lombardi C. , Iriondo J. , Altuna A. , Araiz M. 
Published: June 2019

Background:Light‐chain (AL) amyloidosis is the most common form of systemic amyloidosis, accounting for 70% of patients with amyloidosis. It is characterized by deposition of a misfolded monoclonal light‐chain that is secreted from a malignant plasma cell clone, and interferes with an organ's normal function. Clinical features depends on organs involved. To continue improving patient prospects, early and accurate diagnosis and meticulous treatment choices are essential. Immunohistochemistry of abdominal fat aspirates is the most widely available method for amyloid typing, and it has to be done by a highly specialized pathologist, combined with clinical data and genotyping, it may lead to accurate amyloidosis classification. Delayed diagnosis remains a major obstacle to initiating effective therapy.Aims:To describe retrospectively the diagnosis and management in our hospital, of twenty five patients with biopsy‐proven systemic AL amyloidosis (included between 05/2011‐01/2019).MethodsMedian age at diagnosis was 64 years (range 45‐84). 44% patients were male and 56% female. At baseline evaluation, λ free light chains was shown in 92%, median bone marrow plasma cells was 10.9% (5 patients had associated MM), 12% had unfavorable genetic. Mayo stage was distributed as follows: I (8%), II (20%), III (28%), IV (44%). 20 pts (80%) had cardiac involved and 12 (60%) had typical pattern of delayed gadolinium enhancement in magnetic resonance. Median left ventricle thickness was 16.7 mm.Results:The histological diagnosis was in 28% by renal biopsy, 20% minor salivary gland, 16% fat aspiration, 8% cardiac, and proceeds with mass spectroscopy in 2 patients. Fat aspiration was performed in 15 pts (60%), but only 4 (26%) were positive. 44% received one regimen of treatment [0‐6 lines]. Bortezomib and lenalidomide were the most used drugs in first and second line (80% and 32% respectively). 20% underwent ASCT (only 2 directly). 16% received doxycycline. The hematologic and organic response for each line and PFS is shown in table 1. Median PFS was decreasing with Mayo stage (1‐2 stage: 16 month, 3: 9.7 months, 4: 7 months. Median OS was 4 years [95% CI 1.5‐6.4] with median follow up of 7.8 years, and median OS in patients achieving RC/VGPR was 4.9 years [95% CI 1.7‐8].Summary/Conclusion:1) Our series PFS and OS are worse comparing with literature, in real world AL amyloidosis is still diagnosed late, in advance Mayo stage (72%), and cardiac involvement. 2) The fat aspiration is not the diagnosis tool in the most cases. 3) Early diagnosis is the key to managing the disease and improves de survival of these patients. 4) It could be recommendable to start therapy, if clinical‐analytic suspicious is high, although without histological confirmation, but it has to be provided in further studies.image
PB2186 IMPACT OF CYTOGENETIC ABNORMALITIES ON RESPONSE IN A COHORT OF INDIAN MULTIPLE MYELOMA PATIENTS–IS 13Q DELETION THE NEW 17P IN DISGUISE?
Authors: Mirgh S. P. , Mahapatra M. , Seth T. , Dhawan R. , Aggarwal M. , Saxena R. , Pati H. , tyagi S. , Kothari S. , Halder R. 
Published: June 2019

Background:R‐ISS (Revised International Staging System) incorporates cytogenetic abnormalities for risk stratification of multiple myeloma. High‐risk cytogenetic abnormalities in R‐ISS include 17p deletion, t(4;14),t(14;16). Detection of these abnormalities by interphase FISH (Fluorescence in‐situ hybridisation) has become a popular modality owing to its targeted detection ability in non‐mitotic cells.Aims:The aim of this study was to observe the frequency of cytogenetic abnormalities in the Indian setting and their co‐relation with treatment outcomes.MethodsRetrospective single‐centre study conducted at a single tertiary care centre from North India. Multiple myeloma FISH panel comprising of 5 abnormalities ‐ 13q deletion, 17p deletion, t(4;14), t(11;14), t(14;16) were done in all patients with multiple myeloma, either at diagnosis or when they were referred for relapse or progression of disease. Records of patients in the last two years (January 2016 ‐July 2018) were analysed.Results:Over a period of 30months, myeloma FISH panel was done in 49 patients. Of these, abnormalities were detected in 52% (n = 25) patients. 90% patients belonged to ISS stage‐3. FISH panel was done at diagnosis, first relapse and disease progression in 77.5% (n = 38), 7.3% (n = 3) and 19.5% (n = 8), respectively. The most common abnormality was 13q deletion (36.7%). 17p deletion,t(4;14) and t(11;14) were seen in 8.2%(n = 4),4%(n = 2) and 2.4% (n = 1) patients, respectively. Response to treatment could be evaluated in 46 patients which was graded as per IMWG (International Myeloma Working Group) response criteria. The overall response rate (CR/VGPR/PR) of patients in different groups–Normal, 13q deletion, 17p deletion was 79.2%, 50%, 50% respectively. This implied that nearly half of the patients (n = 8) in 13q deletion group did not respond to therapy. Of these, 4 patients (50%) had 13q deletion at baseline. The possible reasons for this may be ‐ detection of 13q deletion in relapsed/refractory patients, concomitant t(4;14) on FISH panel, associated 13q deletion detection on conventional karyotyping and lack of 1q amp detection in our panel which could have let to an unfavourable outcome.Summary/Conclusion:IgH translocations are rare in Indian patients. 13q deletions, akin to the 17p group, are associated with high beta‐2 microglobulin levels (ISS‐3), poor responses to bortezomib based therapy and are seen on disease progression.
PB2193 GENE EXPRESSION PROFILE IN PRIMARY MYELOFIBROSIS: ROLE OF ASXL1
Authors: Sosa S. Sánchez , Sieyro C. Bilbao , Ortega Y. Florido , Pérez E. González , Perdomo M. D. L. N. Saez , Stuckey R. , Santana G. Santana , Labarta M. T. Molero , Ferrer J. F. Loro , Casares M. T. Gómez 
Published: June 2019

Background:Primary myelofibrosis (PMF) is a BCR‐ABL1‐negative myeloproliferative neoplasm characterized by aberrant differentiation of all myeloid lineages and profound disruption of the bone marrow niche. The presence of JAK2, CALR or MPL [R1] mutation supports the diagnosis. In approximately 10% of cases classified as PMF, the genetic cause remains unknown and they are known as triple negative. Recent prognostic scores like GIPSS or MIPSS recommend the analysis of other mutations in non‐driver genes, such as ASXL1, SRSF2, EZH2, IDH1/2 and U2AF1Q157, since they influence the risk stratification.Aims:To analyze the mRNA expression profiles of EZH2, ASXL1, RB1 and TET2 genes in a series of PMF patients with known mutational status of JAK2V617F, CALR and MPL
MethodsOur series consisted of 21 PMF patients, 6 females and 15 males, with a mean age of 70 years (range 41–87), diagnosed and treated between 1996 and 2018 at the Hospital Universitario de Gran Canaria Dr. Negrín, Spain. Four patients of our series were triple negative, 13 JAK2V167mut, 3 CALRmut and 1 MPLmut. mRNA expression levels were determined by real time PCR in a LightCycler 480 Instrument II (Roche) using ABL as a control gene. Results were normalized with a cDNA pool from the peripheral blood of 10 healthy donors, which was introduced as an internal control in each experiment. SPPS V.23 software was used for statistical analyses.Results:We found that ASXL1 expression levels were significantly higher in patients with JAK2V617F mutated compared with JAK2V617F non‐mutated (mean 0.47 vs. 0.25, p = 0.037, Mann–Whitney U test). In the study of progression free survival, we detected a 36% decrease in the probability of progression to AML or death per unit of ASXL1 expression (p = 0.007, Cox regression test). No significant associations were found between expression levels of the other genes studied (RB1, TET2 and EZH2) and triple negative status.Summary/Conclusion:ASXL1 mutations are common in myeloid diseases and, in these cases, ASXL1 mutations are associated with worse overall survival and leukemia‐free survival. While the impact of ASXL1 mutations has been well‐studied, the impact of ASXL1 expression levels on patient outcome is less studied. The positive association between higher ASXL1 expression plus JAK2V617Fmut and better progression free survival is in agreement with the fact that the opposite, that is, inactivating ASXL1 mutations plus triple negative status, contribute to poor prognosis. These preliminary results should be confirmed in further studies with a larger series.
PB2196 ANTIPLATELET THERAPY IN ESSENTIAL THROMBOCYTHEMIA: LABORATORY STUDY OF LOW‐DOSE ASPIRIN
Authors: Cacciola R. , Vecchio V. , Cacciola E. Gentilini , Cacciola E. 
Published: June 2019

Background:The essential thrombocythemia (ET) is a myeloid neoplasm characterized by platelet hyperreactivity and thrombosis. The daily low‐dose aspirin (ASA) is a cornerstone in the prevention of the thrombotic events. In the ET an accelerated platelet turnover translates in a renewal of the drug target shortening the duration of cyclooxygenase (COX‐1) inhibition and may dictate new dosing strategies particularly in ASA “low‐responders” patients.Aims:Therefore, we evaluated platelet count, β‐thromboglobulin (β‐TG) and platelet factor 4 (PF4), as markers of platelet activation, the platelet function activity (PFA), as indicator of ASA platelet sensitivity, the clotting time (CT), clot formation time (CFT) and maximum clot formation/firmness (MCF), as indicators of aspirinated platelet contribution to clot firmness.MethodsWe studied 60 patients (20 men, 40 women; mean age 51 years, range 32‐70) with ET according to WHO criteria. The mean duration of disease was 11 years. All patients were on ASA 100 mg once daily. Of the 60 patients, 45 were on anagrelide hydrochloride (daily dose 1.5 mg) (10 men, 35 women), 15 were on hydroxyurea (daily dose 2 mg) (10 men 5 women). None had inherited or acquired thrombotic risk factors. Sixty subjects served as controls. Platelets were measured by automated analyzer. β‐TG and PF4 were determined by ELISA. ASA platelet sensitivity and CT, CFT and MCF were measured by Platelet Function Analyzer (PFA‐100) and by ROTEM delta, respectively.Results:The mean platelet count was 455 ± 200 × 109/L. All patients had normal β‐TG and PF4 (12 ± 5 IU/ml and 4 ± 1 IU/ml), prolonged C/EPI closure time (T, unit: s, n.v. 84‐160 s) (249 ± 40 s), normal CT (CT, unit: s. n.v. 100‐240 s) (110 ± 20 s), normal CFT (CFT, unit: s, n.v. 30‐110 s) (45 ± 5 s) and normal MCF (MCF, unit: mm, n.v. 50‐72 mm) (61 ± 2 mm).Summary/Conclusion:These findings suggest that in ET patients the daily low‐dose ASA represents an optimal dosing strategy.
PB2213 SPLANCHNIC VEIN THROMBOSIS IN MYELOPROLOFERATIVE NEOPLASMS; A PROSPECTIVE ANALYSIS OF THROMBOSIS OUTCOME
Authors: Danaee A. , Yu D. , Chen F. , Patch D. , Tripathi D. , Karkhanis S. , Sekhar M. 
Published: June 2019

Background:Splanchnic vein thrombosis (SVT) includes extrahepatic portal vein obstruction (EHPVO), Budd‐Chiari syndrome (BCS) and mesenteric vein thrombosis. Myeloproliferative neoplasms (MPN) account for the majority of non‐cirrhotic SVT and are diagnosed in 30% of patients with EHPVO and 40% with BCS. SVT in MPN patients is associated with significant morbidity and mortality. There have been no prospective studies looking at this subset and there is very little in the way of guidance in managing this complex patient group.Aims:MASCOT is a prospective observational longitudinal study of patients with MPN related splanchnic vein thrombosis. The primary end points of the study are to describe morbidity/portal circulation in the patient group over 18‐24months from baseline, assess any changes in end points clinically and radiologically.Methods:29 patients from two centres were recruited and followed up for 24 months. Radiological primary endpoints, examined changes in initial thrombus, including thrombus extension or recurrence, recanalization in patients without cavernoma and changes in spleen size.Results:The male: female (M:F) was 13:16 with an average age of 48 years (25‐72). The majority of patients had an underlying diagnosis of polycythaemia vera (PV) 13 (45%), followed by essential thrombocythaemia (ET) 9 (31%) and the remaining patients had primary myelofibrosis (PMF), MPN‐unclassified (MPN‐U), post essential thrombocytosis‐MF (PET‐MF). Two patients did not have evidence of MPN on bone marrow histology. 27/29 had the JAK2v617f mutation; 2 had CALR mutation.Summary/Conclusion:In this prospective study of patients we did not observe recurrence or extension of SVT, however a small proportion of patients went on to develop further thrombotic complications whilst on anticoagulation. The study aims to follow patients for duration of five years with repeat imaging and clinical data.
PB2225 ARTIFICIAL INTELLIGENCE AIDING IN DIAGNOSIS OF JAK2 V617F NEGATIVE PATIENTS WITH WHO DEFINED ESSENTIAL THROMBOCYTHEMIA
Authors: Belcic T. , Cernelc P. , Sever M. 
Published: June 2019

Background:Smart Blood Analytics (SBA) is an artificial intelligence program using machine learning algorithm in order to provide a list of most probable disease diagnosis in numerical order based on patient's blood test results. It was successfully tested in diagnosing hematological diseases and is especially targeted for medical doctors without detailed knowledge in the field of hematology.Aims:Our aim was to determine the applicability of SBA algorithm in patients with suspected essential thrombocythemia (ET).Methods:We analyzed 237 patients that presented at UMC Ljubljana between 04/2011 and 09/2016 with the referral diagnosis of ET. Based on the presence of CALR or MPL mutation and bone marrow examination we defined patients with true ET according to WHO 2008 or modified WHO criteria. All 237 patients were subsequently analyzed by SBA algorithm in order to determine the most probable hematologic diagnosis based on patients’ blood test results obtained at the time of referral. The diagnosis of interest according to ICD10 classification was D47 describing other neoplasms of uncertain behavior of lymphoid, hematopoietic and related tissue, including ET. We defined sensitivity and specificity of ET diagnosis by using SBA machine learning algorithm.Results:10.5% (25/237) of patients were diagnosed with ET according to WHO 2008 or modified WHO criteria. 22 patients were CALR positive, 1 patient was MPL positive and 3 patients were triple negative. 89.4% (212/237) of patients were diagnosed with either secondary thrombocythemia or other neoplastic disease, such as myelodysplastic syndrome. The sensitivity of SBA algorithm to detect patients with ET was 100% and the specificity was 50.4%.Summary/Conclusion:The number of patients with true ET referred to our center was low. An improved referral and diagnostic approach for patients with thrombocythemia should be used. The SBA machine learning algorithm could be useful, especially in circumstances where hematologic consultation is not available. Further development of SBA machine learning algorithm is warranted.
PB2237 THE RED BLOOD CELL COUNT AND THE SEDIMENTATION RATE IN THE DIAGNOSIS OF POLYCYTHAEMIA VERA?
Authors: Skov V. , Nersesjan V. , Zervides K. A. , Kjaer L. , Sørensen A. L. , Hasselbalch H. C. 
Published: June 2019

Background:This retrospective cross‐sectional study investigated the effects of microcytosis on the hematocrit (HCT) value in Polycythemia Vera (PV) patients. Since iron deficiency is frequent in PV, and the HCT is a derived value from the Red Blood cell Count x Mean Corpuscular Volume (RBC x MCV), it is reasonable to question if low MCV in PV affects the validity of the HCT value. In addition, we evaluated the Erythrocyte Sedimentation Rate (ESR) as a possible additional diagnostic marker for PV.Aims:To evaluate RBC, hematocrit and the ESR in the diagnosis of PV.Methods:This study included 182 subjects (39 with PV, 27 with Essential Thrombocythemia (ET) and 116 suspected of MPN disease with a secondary cause for either thrombocytosis or erythrocytosis (hereafter named “MPN‐suspects”). The frequencies of microcytosis and low ferritin (<15ug/L) in PV patients were compared to subjects suspected of having a MPN disease. Correlation studies were performed to compare the HCT versus RBC in all subgroups. The ESR was evaluated as a diagnostic marker for PV by a contingency table and a ROC‐curve analysis.Results:In the MPN suspects, 4 of 117 (3 %) had plasma ferritin < 15 ug/L, compared with 6 of 38 (16 %) in the PV‐group (P < 0.05). In the MPN suspects, we found that 3 of 115 (3%) as compared to 6 of 39 (15%) in the PV‐group had MCV < 82 (p < 0.05). Poor linear correlations of RBC versus HCT were found in the PV group compared to the MPN suspects (R2 = 0.62 and R2 = 0.76, respectively). When subjects with microcytosis were excluded, better correlations were observed (R2 = 0.87 in PV and R2 = 0.82 in the MPN suspect group). We found a specificity of 97,7% and a sensitivity of 37,1% for ESR < 2 mm by a ROC‐curve analysis when used for diagnosing PV when PV was suspected. The area under the curve (AUC) was 0,71 (95% CI: 0.60‐0.82), indicating a fair test accuracy for ESR as a diagnostic test.Summary/Conclusion:The HCT is not a valuable parameter in the assessment of expanded RCM in PV, since HCT is falsely lowered due to iron deficiency with microcytosis, which are common findings in patients with PV. The RBC is a simple measurement that may more precisely reflect the total red cell mass which also impacts the ESR as reflected by a low ESR (< 2 mm) in 13 of 35 (37 %) of PV patients at the time of diagnosis. Importantly, the ESR might also be a valuable diagnostic biomarker for PV with a high specificity in patients with elevated HCT, Hb or RBC. A combination of RBC and ESR as simple measures to substitute the Hb‐concentration and the HCT in the diagnosis of PV should be addressed in future well‐designed prospective studies, including the value of the RBC and the ESR in deciding when to phlebotomize patients with PV.
PB2248 FIRST KOREAN CASE OF THROMBOCYTHEMIA 1 WITH THPO MUTATION (C.13+1G>A, SPLICING) DIAGNOSED BY TARGETED EXOME SEQUENCING
Authors: Jung N. , Shim Y. J. , Kim H. S. 
Published: June 2019

Background:Thrombocythemia is a kind of myeloproliferative disorder characterized by excessive platelet production and increased numbers of circulating platelets. Thrombocythemia is also associated with thrombotic or hemorrhagic episodes and leukemic transformation. Thrombocythemia 1 (THCYT1) is a very rare autosomal hereditary thrombocythemia caused by heterozygous mutation in the thrombopoietin gene (THPO) on chromosome 3q27.Aims:We introduce the first Korean boy who was confirmed as thrombocythemia 1 with a THPO gene mutation by next generation sequencing.Methods:We performed targeted exome sequencing to find out genetic cause to induce thrombocytosis. Library preparation was performed by the TruSight One sequencing panel (Illumina, USA). Massively parallel sequencing was conducted by NextSeq (Illumina, USA). An identified variant was confirmed by Sanger sequencing of the patient and his parents.Results:A 25 day‐old male infant who had congenital absent distal phalanges of left hand was referred to our medical center for the evaluation of leukocytosis – white blood cell (WBC) count 32,700/ μL. His older sister had a history of persistent thrombocytosis with unknown etiology from her age of 5 months in another hospital. In his laboratory test, WBC count gradually increased to 57,610/μL and the monocyte count in peripheral blood increased over 1,000/μL. His bone marrow study showed increased myeloid series with some blasts (5.1%). At first, we suspected that he had juvenile myelomonocytic leukemia (JMML), but his clinical and genetic evaluations were insufficient for the diagnostic criteria of JMML. He was followed up for laboratory tests at the outpatient clinic regularly. At his 4 months of age, leukocytosis resolved spontaneously. On the other hand, platelet count increased to more than 1,000,000/μL and sustained. The second bone marrow study revealed megakaryocyte hyperplasia. The genetic evaluations for ET (JAK2, MPL, and CALR gene sequencing) were performed, and there was no pathogenic variant in them. Based on his history and laboratory findings, we performed targeted exome sequencing for his family. Finally, at the 11 months of his age, the patient was confirmed as THCYT1 with a THPO gene mutation (NM_000460.2:c.13+1G>A, splicing) which is also found in his father, as mosaicism, and his sister who was had a history of thrombocytosis. Also, of the 4 of his family, thrombocytosis was only detected in his older sister. The pedigree suggested that the disease was in herited in an autosomal dominant manner. He has been followed over a period of 15 months up to now with treatment of low dose acetyl salicylic acid. No thrombotic or hemorrhagic events developed during the follow up period.Summary/Conclusion:This is the first report of thrombocythemia 1 patient with THPO gene mutation in Korea.image
PB2254 QUALITY OF LIFE AND DEMOGRAPHICS OF PATIENTS WITH IMMUNE THROMBOCYTOPENIA (ITP); DATA FROM THE PLATELET DISORDER SUPPORT ASSOCIATION (PDSA) PATIENT REGISTRY
Authors: Kruse A. , Kruse C. , Potthast N. , Boulanger V. , Seebald A. , Rossov S. , Milligan K. 
Published: June 2019

Background:Patients with the autoimmune disease ITP suffer from bleeding events as a result of low platelet counts. These events may manifest as bruises, petechiae, blood blisters, bloody stools, blood in urine, or even bleeding in the brain. Treatments vary by severity of disease but include medications (steroids, immunosuppressants, IVIG, TPO‐receptor agonists) and splenectomy. Both the disease and the treatments themselves impact quality of life for these patients, who commonly state concerns of anxiety and fatigue.Aims:In 2017, PDSA in collaboration with NORD launched the ITP Natural History Registry to understand patient characteristics, their disease, disease management, and quality of life. Here, we describe the demographics and quality of life for registrants to date.Methods:The PDSA Registry contains 6 surveys covering patient demographics, medical and diagnostic information, treatment utilization, disease progression, and quality of life. As of February 2019, 538 patients have completed 1,975 surveys.Results:Patients in the registry are mostly white (89%, 470/528), female (76%, 399/528), and reside in the US. 34% (170/499) of patients have Medicare, Medicaid, or both, while 62% (311/499) have commercial insurance. Average (median) age at diagnosis was 32 (31) years with 25% (125/502) younger than 18 years. Time from onset of symptoms to diagnosis was more than one year for 32% (169/528) of patients. In response to specific questions regarding anxiety and fatigue, 11% (32/285) of patients stated they were often or always feeling like they needed help for their anxiety and 36% (99/277) said that their fatigue bothered them quite a bit or very much. Of the 538 registrants, 288 provided data on treatment and 27% (78/288) indicated receiving a splenectomy. For patients who received a splenectomy, quality of life was rated as poor to fair for 23% (18/78) of patients. For patients who had not had a splenectomy, 19% (40/210) rated their quality of life as poor to fair, which is improved but not statistically different from the splenectomy group (z = 0.758, p = 0.447).Summary/Conclusion:Respondents in the PDSA ITP Natural History Registry are predominantly female, white, and diagnosed while young, with a fourth of patients under 18 at time of diagnosis. Disease awareness is suboptimal as indicated by the prolonged time to diagnosis, >1 year, for a third of registrants. QoL is impacted in patients with ITP with it directionally worse, though not significantly different, for those who have had a splenectomy compared to those without. Data collection continues through the registry with the intent of raising disease awareness and understanding the impact of the disease.