bluuebunny/crossref_metadata_2025_split huggingface dataset:
PB2200 PREVALENCE OF JAK2V617F, CALR AND MPL MUTATIONS IN PATIENTS OF MYELOPROLIFERATIVE NEOPLASMS AND SPLANCHNIC VEIN THROMBOSIS IN INDIA
Authors: J.  , Arya V. , Gupta N. , Arora A. , Sharma A. , Kotwal J. 
Published: June 2019

Background:Recurrent somatic mutations in the JAK2, MPL, and CALR genes have been described in patients diagnosed with Philadelphia‐negative Myeloproliferative neoplasms (MPNs), including Polycythemia vera (PV), Essential thrombocythemia (ET) and Primary myelofibrosis (PMF). MPN is also the most common etiology in splanchnic vein thrombosis (SVT). MPNs account for approximately 40% of Budd Chiari syndrome (BCS) and 31% of portal vein thrombosis (PVT).The present study was aimed at studying the prevalence of JAK‐2V617F, MPLW515L/K and CALR exon 9 mutations in BCR‐ABL1 negative myeloproliferative neoplasms (MPNs) and splanchnic vein thrombosis (SVT) patients. There is paucity of such data in the Indian patients.Aims:The study had two aims:
Identification of incidence of JAK2V617F, CALR exon 9 mutations and MPLW515L/K mutations in BCR‐ABL1 negative MPNs in India
Identification of incidence of JAK2V617F, CALR exon 9 mutations and MPLW515L/K mutations in Indian patients of SVT
MethodsA total number of 60 patients of SVT and 59 MPN patients (10 PV, 19 ET, and 30 PMF) were included in the study. The mutation analysis for JAK2V617F, CALR exon 9 and MPLW515L/K mutations were performed using the Allele specific oligonucleotide‐polymerase chain reaction (ASO‐PCR) was used to detect JAK‐2, CALR and MPL mutations.Results:Among 59 patients of MPNs and 60 SVT; JAK‐2 mutation was found in 61.0% (36/59) and 23.3% (14/60) respectively. On sub‐classification, JAK‐2 mutation was detected in 80.0% (8/10) of PV; 42.1% (8/19) of ET and 66.7% (20/30) of PMF patients.All the patients of MPNs and SVT were subjected to CALR mutation analysis. The overall rate of CALR mutations in PMF and ET was 10% (3/30) and 21.0% (4/19) respectively. Limiting the analysis to JAK2V617F negative patients of PMF and ET, it was seen that 30% (3/10) PMF and ∼36.36% (4/11) ET cases were CALR mutated. Of these 7 CALR mutations; L367fs∗46 (type‐1) and K385fs∗47 (type‐2) mutations were found in 5 and 2 patients respectively. MPL mutation was identified in 5.26% (1/19) ET cases. Triple negative ET and PMF were ∼31.5% (∼6/19) and ∼23.3% (7/30) respectively. None of the SVT patients were observed to be CALR mutated and none showed the MPLW515L/K mutations.Summary/Conclusion:Indian patients exhibit a lower incidence of CALR mutations in Primary myelofibrosis than that seen in the western literature. However, the incidence of CALR mutations is the same as that reported earlier in Indian patients of Essential thrombocythemia. Triple negative cases constitute 31.5% of all cases of Essential thrombocythemia and 23.3% of Primary myelofibrosis Indian patients show a Testing for CALR mutations and MPLW515L/K mutations in splanchnic vein thrombosis is not justified.
PB2207 EARLY SPLEEN RESPONSE IS A GOOD PROGNOSTIC FACTOR OF RUXOLINIB OUTCOME IN PATIENTS WITH MYELOFIBROSIS
Authors: Lomaia E. , Siordiya N. , Dimov G. , Senderova O. , Mihalev M. , Furtovskaya A. , Ochirova O. , Li O. , Trizna K. , Otmorskaya A. , Sokurova E. , Khazieva A. , Zaritskey A. 
Published: June 2019

Background:Ruxolitinib(RUXO) improves long‐term prognosis in patients(pts) with primary or post‐polycythemia/post‐thrombocythemia myelofibrosis(MF). The most patients experience spleen response. Meanwhile there are a few data how the speed of spleen response in MF affects RUXO treatment outcome.Aims:Evaluate prognostic significance of early spleen response on results of RUXO treatment in patients with MF and assess the factors associated with spleen response.Methods:In the multicenter real world ptactice study 42 patients (male 18, 43%) with MF and spleen data available at least at 3 months were included. Median age at the time of RUXO initiation was 55(25‐75)yrs. Median time from MF diagnosis to RUXO was 52(2‐346)mos. Median time on RUXO was 29 (4‐81)mos. Spleen response(SR) was assessed by palpation. Median spleen length before RUXO was 19(5‐33 cm) with massive spleen >10 cm in the most pts ‐ 36(86%). Constitutional symptoms had 40(95%) of pts. DIPSS score was low, inter‐1 or inter‐2/high in 1(3%), 23(59%) and 15(38%) of 39 evaluable pts.Results:Spleen length reduction at 3mos was: <25% in 13(31%)(Group 1), 25‐<50% in 14(33%) (Group 2) and ≥50% in 15(36%)(Group 3) pts. At 6 mos 3/12(25%) and 3/14(21%) evaluable pts from Gr1 and Gr2 improved their SR. Some more pts from these groups experienced spleen reduction later, but mainly in case of RUXO dose elevation. SR, assessed according to IWG‐MRT criteria, was 13/42(31%) and 17/41(41,5%) in evaluable pts at 3mos and 6 mos, respectively. In all groups a few pts lost their SR. RUXO was stopped in 11(26%) pts, mainly due to disease progression or/and death. Depth of sSR significantly correlated with overall survival. All pts of Gr3 remained alive, whereas 7/29(24%) pts dead in Gr2 and Gr3 overall(p = 0,021). Less pts in Gr3 had huge spleen(>20 cm), blasts 1% or more, low hemoglobin and were treated with low RUXO dose. There were equal symptoms burden in in different groups (Table 1).Summary/Conclusion:The majority of pts respond to RUXO. Depth of SR at 3 mos significantly influenced RUXO long term outcome – all pts with >50% of spleen reduction at 3 mos are alive. It seems that pts with higher dose of RUXO, no periferal blasts, less spleen size and higher hemoglobin level are more responded to RUXO. Larger cohort of pts is needed to confirm statistical significance of this data.image
PB2215 HOW TO PREDICT RESPONSE TO RUXOLITINIB IN PATIENTS WITH MYELOFIBROSIS
Authors: Montero M.I. , Reinoso M. , Pérez‐Ortega L. , Márquez F.J. , Rodríguez‐Arbolí E. , Rodríguez N. , Falantes J.F. , Espigado I. , Pérez‐Simón J.A. 
Published: June 2019

Background:Myelofibrosis (MF) is a classical myeloproliferative neoplasm characterized both in its primary and secondary form by splenomegaly, constitutional and disease‐related symptoms as well as by cytopenias. Aberrant constitutive activation of the JAK‐STAT pathway is core to its pathogenesis and the inhibitors of this pathway such as ruxolitinib, approved for MF treatment seven years ago, have been proven effective in a majority of patients.Aims:To describe ruxolitinib response and median survival in a group of patients diagnosed with MF in a single center and correlate it with the molecular profile, hematimetric data and previous myeloproliferative neoplasm (polycythemia vera (PV) or essential thrombocytosis (ET)).Methods:Of a total of one‐hundred twenty four patients diagnosed with MF in our center, thirty eight patients were treated with ruxolitinib between April 2012 and September 2018. Diagnosis of myelofibrosis was made based on bone marrow examination and according to the updated WHO criteria. Molecular study was carried out in peripheral blood for the mutation JAK2V617F as well as allele‐specific PCR for mutations type 1 and type 2 of exon 9 of calreticulin (CALR) gene, and exon 10 of myeloproliferative leukemia virus (MPL) gene. The prognostic risk stratification was carried out according to the International Prognostic Index (IPSS). All patients treated with ruxolitinib belonged to the intermediate group‐2 or were classified as high risk. Statistical analyses were performed in SPSS 15.0.Results:Average age of the group was 63 years (range 36‐88). 58% were males and 42% female. Average leukocyte, haemoglobin and platelet counts at diagnosis were 9,8x10e9/l (1.9‐62), 10.3 g/dl (6‐15.7) and 236x10e9/L (52‐789), respectively. 47% of patients had a previous diagnosis of another MPN (50% PV and 50% ET). JAK2V617F mutation was present in 70.3%, and CARL and MPL mutation in 12.5% and 2.6%, respectively. All patients responded to ruxolitinib although 39% finally lost this response, with a 13% evolution to acute leukemia, 40% of this group being subjected to allogeneic SCT. Currently, 73% of patients are alive. Six‐year overall survival of patients with JAK2V617F mutation was 80% compared to 60% of those with wild‐type mutational status, statistical significance not being reached. Patients with previous MPN also had greater six‐year overall survival (70%) than those with idiopathic MF (56%).Summary/Conclusion:Patients with MF with JAK2V617F mutation and previous MPN present a greater duration of response to ruxolitinib than others, probably due to greater inhibition of the preponderant pathogenetic mechanism and the more effective action of the drug on a more differentiated progenitor than in idiopathic MF, although broader studies are required to confirm these results.
PB2219 EFFECTS OF SYSTEMIC MASTOCYTOSIS ON BONE HEALTH IN SOUTH‐EAST SCOTLAND
Authors: Peters N. , Teh C.‐H. , Seth S. 
Published: June 2019

Background:Systemic mastocytosis (SM) is a rare condition characterised by excess mast cell production and often involves multiple organs. One organ system becoming increasingly recognised as being affected by systemic mastocytosis is the skeletal system, with reports of increased prevalence of osteoporosis, osteopenia and osteosclerosis represening the main findings.Aims:We aimed to assess the extent of bony involvement of SM in patients in our area, South‐East Scotland who had been referred to the Haematology services in NHS Lothian in order to help guide local policies regarding assessment of bone health upon a diagnosis of systemic mastocytosis.Methods:Clinical records of patients with a diagnosis of SM referred to our services in NHS Lothian available on our local TRAK system were interrogated to investigate for the presence of osteoporosis, osteopenia, osteosclerosis. Further, where available, DEXA bone scan results were tabulated.Results:We identified 18 patients with a diagnosis of SM with multiple variants identified including indolent (15/18), cutaneous, Aggressive with myelofibrosis (1/18) and SM with eosinophilia (1/18) and unclassified (1/18). It was found that 12/18 patients had evidence of osteoporosis (6/18), osteopenia (5/18) or osteosclerosis (1/18) representing a significant disease burden. Further, 13 of the 18 patients had a DEXA scan meaning there is a large portion of patients not being investigated routinely for bony involvement. The average age of patients with osteoporosis and SM was 60 years old with a range from 41 to 74, suggesting a profound effect on bone health at an early age.Summary/Conclusion:We have identified a significant proportion of patients with SM having bony involvement. It has been suggested that DEXA scans form part of initial workup of these patients upon diagnosis, with bisphosphonates used as a first line treatment. The findings of our study support the proactive investigation of bone health in SM.
PB2220 SURVIVAL OUTCOME OF HIGH‐RISK PATIENTS WITH MYELOFIBROSIS TREATED WITH ALLOGENEIC HEMATOPOIETIC CELL TRANSPLANTATION FOLLOWING REDUCED‐INTENSITY CONDITIONING REGIMENS
Authors: Lee J. , Yoon J.‐H. , Yoon S. Y. , Kim C. , Park S.‐S. , Kim H.‐J. , Lee J. W. , Lee S. , Eom K.‐S. 
Published: June 2019

Background:Allogeneic hematopoietic cell transplantation (allo‐HCT) is the only curative treatment for myelofibrosis (MF), but substantial risk of transplantation‐related mortality (TRM) is a considerable obstacle especially in elderly patients or in patients with severe comorbidity. In the era of Janus kinase (JAK) inhibitors, transplantation may be delayed in good responders but cytopenia is a major complication, and we confront refractory patients who should be treated with allo‐HCT immediately.Aims:Here, we are going to show our experiences on high‐risk MF patients who were treated with reduced‐intensity conditioning (RIC) allo‐HCT.Methods:Here, we are going to show our experiences on high‐risk MF patients who were treated with reduced‐intensity conditioning (RIC) allo‐HCT.Results:All showed successful engraftment. Including 2 patients who were conditioned with nonmyeloablative regimen, total 6 (15.8%) showed delayed graft failure at a median 8 months post‐HCT (range, 3.8‐13.8). Two recovered after stem cell booster from the same donor, other 2 received donor lymphocyte infusion but showed progression, and 1 died after 2nd allo‐HCT. Among the 33 patients with post‐HCT bone marrow (BM) exam results, 29 (87.8%) showed significant improvement of BM fibrosis (range, 14‐661 days). After median follow‐up duration of 24.6 months (range, 6.1‐124.8), 2‐year OS was 64.6% (64.3% in triple‐negative subgroup), 2‐year nonrelapse mortality was 27.4%, and 2‐year graft‐and‐relapse‐free survival (GRFS) was 28.4%, which suggested there were fatal high‐grade GVHD in this cohort. Acute GVHD was observed in 18 patients (5 grade II, 7 grade III, 4 grade IV) and a cumulative incidence of grade III‐IV acute GVHD was 30.6%. Chronic GVHD was observed in 13 (4 mild, 2 moderate, 7 severe), and a cumulative incidence of severe chronic GVHD was 27.5%. Among them, severe hepatic GVHD was observed in 9 patients (5 acute, 4 chronic). Among 11 dead patients, 7 died due to fatal hepatic GVHD, 1 died of lung GVHD, and 3 died due to septic pneumonia. Multivariate analysis revealed 2‐year OS was significantly poorer in patients who suffered from hepatic GVHD (HR = 9.8, 95%CI 1.0‐94.7, p = 0.022) and the significant cause of fatal hepatic GVHD was unrelated or mismatched donor HCT.Summary/Conclusion:RIC allo‐HCT can be a valid choice providing graft‐versus‐myelofibrosis effect for advanced and triple‐negative MF patients, but fatal hepatic GVHD was frequently observed especially in unrelated or mismatched donor transplants which should be overcome in the future.
PB2242 COMPARISON BETWEEN MANUAL AND AUTOMATED PLATELET COUNTS OF ADULT PATIENTS WITH THROMBOCYTOPENIA AT ST. PAUL'S HOSPITAL ILOILO (SPHI), PHILIPPINES
Authors: Castromayor J. , Cadete L. Agreda‐ 
Published: June 2019

Background:Platelets are more difficult to count compared to other blood cells. Platelet counting is a significant tool used in clinical investigation to prevent bleeding complications. There is a general agreement that automation bring precision and accuracy for platelet counts in healthy individuals. Automation of platelet counting has been embraced in most part of the world, particularly in more developed countries. However, manual platelet counting & estimation is still being done by skilled medical technologist to generate platelet results in most developing countries like ours. The method of platelet counting in thrombocytopenic patients is still controversial.Aims:To compare if there is significant difference between automated and manual platelet counts of adult patients with thrombocytopenia at the clinical laboratory of Saint Paul Hospital Iloilo City, Philippines.Methods:This is a retrospective‐analytical study of 384 samples of complete blood count (CBC) results with thrombocytopenia that contain both automated and manual platelet count values.Results:Out of the 384 adult patients with thrombocytopenia, there was an approximately 1:1 ratio based on sex. Thrombocytopenia was most common between 6th to 8th decades of life affecting 36% of patients. The mean of the automated platelet levels was approximately 76 × 109/L with the standard deviation of 45; while the manual platelet count results was 170 × 109/L with the standard deviation of 99. Among adult patients with thrombocytopenia, there was a significant difference between manual and automated platelet count results with p value < 0.05).Summary/Conclusion:Thrombocytopenia affect both male and female sex equally. The higher the age group, the higher is the incidence of thrombocytopenia. Manual platelet counts are highly variable compared to the automated values. There was a significant difference between manual and automated platelet count results.
PB2246 CLINICAL FEATURES AND TREATMENT OUTCOMES OF IMMUNE THROMBOCYTOPENIC PURPURA IN INFANTS; A SINGLE CENTER RETROSPECTIVE STUDY
Authors: Park K. M. , Yang E. J. , Lim Y. T. 
Published: June 2019

Background:Immune thrombocytopenic purpura (ITP) in children less than one year of age is less well characterized compared to ITP in toddlers and school‐age children.Aims:Since children of different ages may have differing clinical courses, better delination of the natural history of ITP in infants is needed.Methods:We retrospectively reviewed the admission records of 248 consecutive pediatric patients between 1 month and 15 year of age admitted and treated for acute ITP at Pusan National University Children's Hospital from 2009 through 2017. All of these patients less than 1 year of age were identified and enrolled. We investigated their demographics, clinical features, laboratory examinations, respond to treatment and long‐term outcomes and compared to those of children 1 to 10 years of age.Results:Ninety nine infants were identified. Male to female ratio was highest in infants and decreased with age. Seventy nine (79.8%) of the 99 infant were found to be under 6 months old. The median platelet counts at diagnosis was 6 x 109/L (0∼76). Minor bleeding (bleeding score 0‐2) was significantly dominant in infant compared to older ages. Eighty two out of 85 patients (96.5%) achieved complete remission after initial intravenous immunoglobulin(IVIG) treatment. The relapse rate after initial CR was significantly lower than older ages (p = 0.003). The platelet count after IVIG treatment in infant showed more rapid rising compared to older ages (p = 0.02), and the mean time to platelet counts above 100x109/L was 6.4+4.5 days. Follow up information at 6 months was available for 85 infants. Chronic ITP at 6 month was seen less frequently in infants (4.7%) than in children 1 to 10 years of age. (23.2%. P < 0.01).Summary/Conclusion:Infants with acute ITP respond more favorably to IVIG treatment and are less likely to develop chronic ITP compared to children 1 to 10 years of age.
PB2255 ADULT ITP PATIENTS TREATED WITH ROMIPLOSTIM IN DAILY CLINICAL PRACTICE: SINGLE CENTER EXPERIENCE
Authors: Janssens A. , Vergote V. , Schoemans H. , Beckers M. , Devos T. , Dierickx D. , Delforge M. , Maertens J. , Verhoef G. , Vandenberghe P. 
Published: June 2019

Background:Since May 2007 we can treat in Belgium adult primary immune thrombocytopenia (ITP) patients with the TPO receptor agonist (TPO‐RA) romiplostim (clinical trials, reimbursed, medical need).Aims:We wondered what the baseline and treatment characteristics of this ITP patient population was.Methods:From May 2007 till May 2018, 60 adult ITP patients started treatment with romiplostim at the University Hospitals of Leuven.Results:The baseline characteristics of this cohort are as follows: 35 of 60 patients were male; diagnosis of primary ITP was made in 42 patients; the 17 patients with secondary ITP had a history of lymphoma (n = 6), Evans syndrome (n = 5), a previous liver or renal transplant (n = 3) or an underlying inherited disorder (n = 3); mean age and platelet count at ITP diagnosis was 53years (y) (range 1‐90y) and 16000/ml; median time between ITP diagnosis and the start of romiplostim was 60months (mo) (range 0‐492mo); at start of romiplostim 7 patients fulfilled the definition of acute, 7 of persistent and 45 of chronic ITP; median platelet count at start of the drug was 20000/ml; 32% (19/59) were splenectomised and 39% (23/59) needed 3 3 ITP treatments (range 3‐8) before the start of the TPO‐RA.At 30 november 2018, median time on romiplostim was 21.5mo (range 2weeks ‐10.5y); treatment was ongoing in 38% (n = 23/60) of patients; reasons for discontinuation was non‐ITP related death (n = 17), ITP related death (n = 1), treatment‐free remission (TFR) (n = 10), patient's decision followed by TFR (n = 2), splenectomy followed by TFR (n = 2), doctor‘s decision (n = 1), loss of response (n = 2) and loss of follow up (n = 1). Median dose of romiplostim needed for a safe platelet count was 3.75 m/kg.Summary/Conclusion:These data show that treatment with romiplostim is not “for all” forever. Non‐ITP related death (median time on drug 20.5mo) and TFR (median time on drug 5mo) were the most common reasons of discontinuation of the drug.
PB2256 DISSOLVED PSEUDO‐THROMBOCYTOPENIA BY USING EVIDENCE‐BASED RESEARCH
Authors: Chen S. H. , suen T. 
Published: June 2019

Background:Platelet clumping is a common laboratory phenomenon that causes pseudo‐thrombocytopenia (PTC), spurious thrombocytopenia due to persistence of antibody or agglutinins. Microscopic examination of the peripheral blood smear is of key importance to confirm the diagnosis and to avoid any inappropriate or dangerous clinical and therapeutic decision. How to dissolve platelet clumping and make sure correct platelet count is an important procedure. Ethylenediaminetetraacetic acid (EDTA) is a well‐known anticoagulant for the hematological tests (CBC). EDTA‐dependent pseudo‐thrombocytopenia is the most common causes of platelet clumping in medical laboratory.Aims:To dissolved platelet clumping ex vivo and correct platelet count in medical laboratory avoid further inappropriate treatment and waste of medical resource.Methods:We drew blood of the patient in three tubes containing three different types of anticoagulants; EDTA, Sodium Citrate and Heparin. The three blood samples were run in fully automated Hematology analyzer (SYSMEX XN‐3000).Three tubes also process in water bath at 37 °C 10 minute and vortex until run automated Hematology analyzer again.Results:54 years old female patient was referred to our lab for investigations as a case of implicated thrombocytopenia. The CBC revealed normal parameters apart from a low platelet count; 35 x10^9/L. A blood smear was ordered and it revealed server platelet clumping. Using different types anticoagulants, EDTA, Citrate, heparin result similar platelet count and still reveal platelet clumping on blood smear. We further pre‐treated warm water bath(37 °C) plus vortex before analysis. Platelet count was counted 138 x10^9/L by automatic hematologic analyzer in pre‐warm blood specimen. The smear also checked by microscopy without phenomenon of platelet clumping.Summary/Conclusion:Platelet cold agglutinin is confirmed by pre‐warm blood specimen which is a rare cause in pseudo‐thrombocytopenia. We used methods of evidence‐based medicine (EBM) to find out patient with cold agglutinins that affect platelet counting.