bluuebunny/crossref_metadata_2025_split huggingface dataset:
PB1956 COEXISTENCE OF BCR/ABL1 AND JAK2 MUTATION IN MYELOPROLIFERATIVE NEOPLASMS
Authors: Luciano L. , Crisci S. , Trastulli F. , Fatigati M. , Izzo B. , Pane F. , Frigeri F. 
Published: June 2019

Background:Chronic Myeloid Leukemia and Myeloproliferative neoplasms were considered mutually exclusive. However some recent reports have described the co‐occurrence of BCR/ABL1 and JAK2 mutation in patients with CML phenotype. Generally, in the few reported cases, clinical and laboratory data suggest the presence of two different clones.Aims:Here we describe the clinical and molecular data of 3 patients showing the presence of BCR/ABL1 and JAK 2 mutation, with CML phenotype in 1 and myeloproliferative phenotype evolving in CML in the others.Methods:BCR/ABL1 transcript were identified and quantified by Rq‐PCR according to ELN recommendations; JAK2 mutation were evidenced by PNA clamping PCR in one patient and by ASO‐PCR in the others.Results:Patient clinical characteristics are summarized in table 1. Patient 1 showed CML phenotype with coexistence of BCR/ABL1 and JAK2 mutation at diagnosis. He started Dasatinib treatment at standard dose (100 mg/die) but after 6 months because of intolerance, he switched to Ponatinib obtaining a major molecular response. Patient 2 was diagnosed Thrombocytemia carrying V617F JAK2 mutation, after a portal vein thrombosis and started anticoagulant therapy combined to Hydroxiurea treatment. After 2 years, he switched to IFN therapy and in 2011 (after 2 more years) he showed CML feature with the appearance of BCR/ABL1 hybrid transcript. Imatinib treatment was added to Interferon and combination therapy was sustained for 7 years. Because of intolerance to IFN, in 2018 patient switched to Ruxolitinib at the dose of 30 mg BID, while also maintaining Imatinib. Patient 3 was diagnosed Thrombocytemia carrying V617F JAK2 mutation in 2009 and received IFN treatment. In 2017 he developed leukocytosis with the appearance of e1a2 BCR/ABL1 hybrid transcript. At that time, he stopped IFN therapy and started Imatinib at the standard dose of 400 mg per day with control of both diseases. Molecular monitoring showed a simultaneous decrease of both abnormalities in patient 1 who got a deep molecular response (MR 4). Patient 2 reached a deep molecular response (MR 4.5) but still needs of Ruxolitinib treatment for thrombocytemia, suggesting the presence of two different clones. Patient 3 got a deep molecular response (MR 5) and it is ongoing the evaluation of JAK2 mutation.Summary/Conclusion:Coexistence of BCR/ABL1 and JAK2 mutation is rarely reported so far but a widely use of molecular techniques could increase the number of patients with both abnormalities. At least in patient 3 of our series, clinical and molecular data suggest that both abnormalities are present in the same clone and V617F JAK2 mutation is the first occurred one. Digital PCR experiments could clarify if a single cell express both molecular abnormalities. Such cases are relevant to better understand the pathogenesis of myeloproliferative neoplasms.
PB1976 MICROANGIOPATHIC HEMOLYTIC ANEMIA DUE TO HEART VALVE PROSTHESIS
Authors: Andrade Luís D. , Afonso S. , Loureiro B. , Silva Gomes J. , Barreira R. , Maia Magalhães T. , Ribeiro M.L. 
Published: June 2019

Background:Microangiopathic hemolytic anemias (MAHA) are characterized by the presence of hemolytic anemia (HA), related to red blood cell (RBC's) fragmentation, thrombocytopenia and hemosiderinuria due the intravascular hemolysis. The term thrombotic microangiopathy (TMA) is also used to describe syndromes characterized by AHMA, thrombocytopenia, and thrombotic lesions in small blood vessels such as Thrombotic Thrombocytopenic Purpura (TTP) and Hemolytic uremic syndrome (HUS). Although TTP and HUS are the prototypes of TMA / MAHA, there are other causes that should not be forgotten, such as MAHA by valvular leak.Aims:Perform the casuistry of the Hematology Service of a Central Hospital for a rare cause of hemolytic anemia.Methods:Parameterized search for the data of patients with MAHA and hemosiderinuria evaluated at a Hematology out patients clinic at a Central Hospital between January 2007 and March 2018.Results:9 patients with MAHA were identified with valvular leak, the mean age at diagnosis was 68 years and 6 were men (66%). All patients had mechanical heart valves: 66% mitral valve, 22% aortic valve and 11% both valves. The time from surgery to diagnosis of AHMA was ∼ 2 years. The mean Hb value was 8.4 mg/dL. All patients had RBC fragmentation. The mean value of DLH was 3773U/L, total bilirubin (TBil) was 1.9 mg/dL. 88% patients were supplemented with oral iron. Only 3 patients increase ∼ 1.5 g of Hb after 3 months of therapy. 1/3 patients were supplemented with EV iron; 1/3 needed blood transfusion. 66% underwent valvular leakage correction and of these 50% significantly improved Hb and hemolysis.Summary/Conclusion:A careful clinical history and the RBC morphology play a central role in the diagnosis of anemia. The MAHA due to leak valvular is a rare entity, but with a tendency to increase. Despite the small number of patients, the authors consider pertinent to present these data because this is a potentially reversible cause of anemia. The disproportionate high DHL level in relation to the TBilis a possible clue to the differential diagnosis of HA.
PB1980 IMPROVING HEALTHCARE PROVIDERS’ KNOWLEDGE REGARDING THE PRINCIPLES OF GENE THERAPY FOR HEMOPHILIA THROUGH ONLINE EDUCATION
Authors: Hurst S. , Warren C. , Kadkhoda H. , VanLaar E. , Pierce G. 
Published: June 2019

Background:Gene therapy offers the hope of a functional cure for hemophilia. To prepare healthcare providers (HCPs) for this potential paradigm shift in care, National Hemophilia Foundation (NHF), European Haemophilia Consortium (EHC), the World Federation of Hemophilia (WFH), and Medscape Education collaborated to develop a multi‐modal, online, continuing medical education (CME) curriculum.Aims:The current study assessed the ability of online CME to improve HCPs knowledge regarding the scientific principles underlying gene therapy overall and its study in hemophilia.Methods:A 15‐minute, CME‐certified video commentary with synchronized slides was developed and launched online on 8/3/2018. Educational effectiveness was assessed with a repeated‐pairs pre‐/post‐assessment study design, in which each individual served as his/her own control. Responses to 3 multiple‐choice, knowledge questions and 1 self‐efficacy confidence question were analyzed. A chi‐squared test assessed changes pre‐ to post‐assessment. P values <0.05 are statistically significant. Effect sizes were evaluated using Cramer's V (<0.05 modest; 0.06‐0.15 noticeable effect; 0.16‐0.26 considerable effect; >0.26 extensive effect).Results:To date, 1634 HCPs (958 physicians) have participated in this activity. This analysis presents data from the subset of hematologists/oncologists (n = 77; hem/oncs) and pediatric oncologists (n = 69) who answered all pre‐/post‐assessment questions during the initial analysis period of 8/3/18‐9/5/18; data collection is ongoing. Significant improvements were observed overall (hem/oncs: P = .0007; V = .156) and in the following areas,‐ Correct identification of transient transaminitis as the most common adverse event observed in gene therapy trials: hem/oncs: 45% vs 73% (62% relative increase), P = 0.0006, V = .277; and pediatric hematologists: 26% vs 43% (% relative increase), P = .032, V = .181‐ Recognition of the relatively low homology between the adeno‐associated virus (AAV) vector used in gene therapy trials for hemophilia A (AAV5) and other primate AAVs: hem/oncs: 36% vs 55% (53% relative increase), P = 0.023, V = .182‐ Pediatric hematologists exhibited a small increase in knowledge, but this change was not statistically significant: 33% vs 41% (24% relative increase), P = NS‐ Both of hem/oncs (39%) and pediatric hematologists (32%) indicated increased confidence in their understanding of the science underlying gene therapy in hemophiliaLastly, the findings uncovered educational needs, such as the understanding of the FIX construct currently under study in hemophilia B trials.Summary/Conclusion:Participation in this online activity significantly improved knowledge among hem/oncs and pediatric hematologists with regard to the adverse events, viral vectors, and gene constructs in current clinical trials for gene therapy in hemophilia.
PB1996 PROGNOSTICATION OF HODGKIN'S LYMPHOMA BY IPET AND IPS: UPDATE DATA OF 8 HEMATOLOGICAL UKRAINIAN CENTERS.
Authors: Novosad O. , Skrypets T. , Pastushenko I. , Kadnikova T. , Ulianchenko K. , Gorbach A. , Ashykhmin A. , Kmetyuk Y. , Karpova O. , Mykhalska L. , Kindrakevych O. , Kozlov V. , Novikov N. , Kosinova V. , Oliinichenko E. , Kostiukova N. , Tkachenko O. , Karnabeda O. , Stratienko V. , Kriachok I. 
Published: June 2019

Background:PET‐CT has completely changed and improved treatment approaches in patients with Hodgkin Lymphoma (HL) for the last years. Recent studies are evaluated predictive role PET for survival rate. The major idea is to identify patients from a high‐risk group who can have early relapse/refractory disease using iPET and IPS to guide the choice of chemotherapy.Aims:To evaluate the prognostic role of iPET in patients with HL.Methods:The cohort consisted of 132 patients of up to 69 years of age with newly diagnosed HL were treated with ABVD or BEACOPP‐14/esc based on their stage and risk group. Metabolic PET‐CT imaging was performed to routine protocols using Deauville criteria for response assessment. Interim PET was performed at 15.5 ± 3 days (range, 5‐26) after 2‐3d and 4th cycles of treatment in 81% and 19% cases, respectively (p < 0.05). The main endpoints of study were to assess the correlation between IPS, iPET findings and clinical outcome (relapse/death).Results:The ORR (CR, PR) in this group of patients was 85.6%. The maximum follow‐up period was 70 months (median 16 months). Under the follow‐up there are still 96.9% (128/132) patients.81.8% (108/132) and 18.2% (24/132) of patients had 1–3 and 4–5 scores of iPET by Deauville 5‐PS scale, respectively (p < 0.05). In total, disease progression was documented in 20.8% (5/24) iPET‐positive (iPET+) and 13% (14/108) iPET‐negative (iPET‐) patients (p < 0.05). There were two deathss from refractory disease. The 5‐year EFS of iPET+ patients vs iPET‐was 50% and 80%, respectively (p < 0.05).We divided patients by IPS groups: 71(53.8%) with ≤2 and 61(46.2%) with ≥3 risk factors (low and high‐risk group, respectively, p < 0.05).Patients in low‐risk group were associated with significant improvement in 5‐year EFS compared with patients in high‐risk group (80% vsthe 65%, respectively, longrank test, p = 0.01).The estimated 5‐year EFS was 80% in iPET‐ vs 65% with iPET+ in low risk group (p < 0.05). The 5‐year EFS was significantly better in high‐risk patients who achieved iPET‐ status compared to iPET+ status (70% vs 55%, p < 0.05).Summary/Conclusion:In our study, we found that IPS correlates with iPET results. Moreover, it could predict treatment outcomes in patients with HL.
PB1998 PROGNOSTIC VALUE OF PRETRANSPLANT PET/CT IN HODGKIN LYMPHOMA
Authors: Dr Miltényi Z. , Punk E. , Dr Pinczés L.I. , Illés Á. 
Published: June 2019

Background:Autologous stem cell transplant (ASCT) is the standard of treatment in patients with refractory/relapsed Hodgkin lymphoma (HL). Several adverse prognostic factors at relapse are known (stage, anaemia, B signs, Karnofsky score, early relapse etc.) to predict the outcome after ASCT.Aims:We analyzed the prognostic value of pre‐ transplant PET/CT and number of salvage therapy retrospectively.Methods:Between January 1, 2007 and December 31, 2018 pre‐transplantation 18FDG‐PET/CT scans of Hodgkin‐lymphoma patients were performed. Deauville criteria were used for evaluation of PET/CT scans. Positive PET scans were defined, if Deauville score was 4 or 5. We analyzed the effect of PET/CT results for survival (overall‐, relapse‐ and event free), and investigated differences between PET positive and PET negative groups. Statistical analysis was performed using IBM SPSS 25 programme.Results:Sixty‐two Hodgkin‐lymphoma patients (33 men and 29 women) had PET/CT scan before AHSCT. Median age at the time of AHSCT was 35 (19‐65) years. Median follow up time was 55.4 (0‐175) months. There were 49 (79%) PET negative and 13 (21%) PET positive patients. Five‐year overall survival rate was 80% in PET‐ group, and 46.2 % in PET+ group (p < 0.042). Five‐year relapse‐free and event‐free survival rate for negative and positive groups were 85.5% and 43.5% (p < 0.012), and 70.3% and 30.8% (p < 0.006). There were 6 relapse and 9 deaths (3 due to HL) in PET‐ group, and 5 relapse and 6 deaths (due to HL) in PET+ group. Twenty‐five of 49 patients in the PET‐ group got only one type of salvage treatment (DHAP) before AHSCT, against 2 of 13 patients in PET+ group (p = 0.046). Patients who acquired PET negative status after DHAP therapy only, had no relapse. Patients who were treated with 2 or more lines of salvage therapy and acquired PET negative status after these treatments, has no significantly better relapse‐free survival, than patients who remained PET positive.Summary/Conclusion:Clinical routine use of PET/CT before AHSCT is highly suggested based on our investigation. PET‐ patients have significantly better OS, PFS and EFS. PET negative status attends better prognosis, if it is reached with first salvage treatment.
PB2002 IMPACT OF AUTOIMMUNE CYTOPENIAS ON THE CLINICAL COURSE AND SURVIVAL OF HODGKIN LYMPHOMA
Authors: Pinczés L. , Szabó R. , Miltényi Z. , Illés Á. 
Published: June 2019

Background:Autoimmune cytopenias (AICP), namely autoimmune hemolytic anemia (AIHA) and autoimmune thrombocytopenia (AITP) often complicate the course of malignant lymphomas. The incidence and clinical significance of AICPs associated with Hodgkin lymphoma (HL) have not been thoroughly defined.Aims:Our aim was to retrospectively assess the incidence, clinical features and response to treatment of HL‐associated autoimmune phenomena.Methods:Five hundred and sixty‐five HL patients were diagnosed and treated at the University of Debrecen between 1990 and 2017. We compared the clinicopathological characteristics of HL patients developing AICPs with those who had no clinical evidence of autoimmune events. We considered an AICP to be a disease‐defining event if it led to diagnosis or revealed disease progression, relapse or secondary malignancy. Statistical analysis was performed using Fisher's exact test.Results:We identified 8 cases of AIHA and 8 cases of AITP among 14 patients altogether, one of them presented with Evans syndrome. Two AICPs preceded the diagnosis of HL, 2 of them developed simultaneously with the disease and 11 AICPs occurred during follow‐up after first line therapy. During more than 5000 person‐years of follow‐up, the incidence of AICPs in HL patients was 2,8%. Eighty‐one percent of AICPs required treatment, 77% of these patients responded well to intravenous steroid. Treatment of the underlying lymphoma with ABVD combination chemotherapy resulted in the effective control of both the underlying disease and the immune condition, in most cases, where AICPs were identified at the presentation of HL. Almost half of the AICPs (46%) were disease‐defining events: 5 cases led to the diagnosis of HL or indicated relapse and 2 events revealed secondary malignancies. AICPs were more frequently observed in patients with advanced stage disease at initial diagnosis (p < 0.004). The association of HL and AICPs had no effect on long‐term overall‐ (OS) and progression‐free survival, however, short‐term (1 year) mortality of HL patients experiencing AICPs was significantly elevated (p < 0.022) compared to the majority of patients, who did not have AICPs. Also, the OS rate of HL patients with AICPs at initial diagnosis was significantly lower (p = 0.033) compared to patients developing AICPs during follow‐up.Summary/Conclusion:While AICPs are rare complications of HL, these events can imply clinical significance. Those HL patients who experienced AICPs had a particular disease‐related profile. These cytopenias show a good response to steroid treatment. This large series of consecutive, unselected patients demonstrate that the association of HL and AICPs may increase short‐term mortality. Our results emphasize the importance of taking into consideration the possibility of an underlying hematological malignancy in newly diagnosed AIHA/AITP cases.
PB2016 RESULTS OF TREATMENT PATIENTS OF MANTLE CELL LYMPHOMA DEPENDING ON THE MUTATIONAL STATUS OF THE TP53 GENE
Authors: Koroleva D. , Zvonkov E. , Gabeeva N. , Smolyaninova A. , Gavrilina O. , Shchetsova O. , Biderman B. , Tsygankova S. , Bulygina E. , Rastorguev S. , Nedoluzhko A. , Sudarikov A. , Kovrigina A. , Galtseva I. , Obukhova T. , Kuzmina L. , Parovichnikova E. , Savchenko V. 
Published: June 2019

Background:According to a retrospective study published data in 2017 by the Nordic MCL group, in multivariable analyses, only mutation TP53 showed independent prognostic impact. The median OS for the TP53‐mutated cases was 1.8 years, median PFS was 0.9 years.Aims:To assess the incidence of TP53 gene mutation and survival in pts with MCL during of prospective trial MCL‐RUS‐2016.Methods:A total 25 pts were enrolled in prospective study MCL‐RUS‐2016 between 2016 to 2019 years. The median age was 52 years (range, 33 to 71 years). Seven pts (28%) were over the age of 60 years. Male:female = 15:10. In all pts the Ann Arbor stage was 4. Among 25 pts in depend pretreatment MIPI score, 36%, 48% and 16%, respectively, were considered as being at low, intermediate and high risk. Seven (28%)of 25 pts had blastoid MCL. Mutation of the TP53 gene determined using by Sanger sequencing of the coding region (exons 1(2)‐11) was present in 4 (16%) pts (TP53mut). Another 21 pts (84%) had wild type mutational status (TP53 wt). Complex karyotype (CK) was indentified in 8 (32%) pts. Three pts had the mutation of p53 and CK. Deletion of 17p was present in 4 (16%) pts, but only 3 of 4 cases with 17p loss displayed TP53 mutation.Results:Eighteen pts (TP53 wt) reseived 4 cycles of alternating of rituximab, bendamustine, cytarabine (R‐BAC) and rituximab, high dose cytarabine 12 g/m2 (R‐HA), followed by stem cell mobilization and ASCT. MRD was not detected in all 18 pts at the end of therapy. Eighteen pts achieved and remain in complete remission and 3 pts continue on treatment. The median follow‐up time was 5 months after ASCT (range, 1‐17 months). Pts with MCL, who have TP53 mutations, had a worse prognosis. Two pts with TP53 mutation in our study died for progression disease. Two pts, who underwent allo‐HCT from non‐relative HLA‐matched donors, is a alive in CR, with the time of observation three and twenty‐seven months.Summary/Conclusion:The regimens R‐BAC/R‐HA was well tolerated with a manageable safety profile. Allogeneic hematopoietic cell transplantation is only curative treatment for MCL with TP53 gene mutation.
PB2021 GASTRIC MUCOSA‐ASSOCIATED LYMPHOID TISSUE LYMPHOMA: A MONOCENTRIC EXPERIENCE
Authors: Ben Kridis W. , Falleh S. , Charfi S. , Khmiri S. , Toumi N. , Boudawara T. , Daoud J. , Khanfir A. 
Published: June 2019

Background:Mucosa‐associated lymphoid tissue (MALT) lymphoma accounts for 7‐8% of B‐cell lymphoma. Tumor proliferation consists of type B lymphomatous cells of low grade malignancy. They are considered indolent and are part of the marginal zone. They constitute the predominant histological type of non‐Hodgkin's malignant lymphoma of the stomach. Transformation into high‐grade lymphoma is rare.Aims:The aim of this study is to describe the clinical characteristics and the therapeutic results of MALT lymphoma.Methods:We reviewed retrospectively the records of 18 patients presenting with gastric MALT lymphoma treated between 1993 and 2018. Patients with low‐grade lymphoma in failure after helicobacter eradication had exclusive gastric external radiotherapy. Chemotherapy were indicated in case of high grade lymphoma transformation. Radiotherapy doses range between 30 and 40 Gy (2 Gy per fraction, five fractions per week).Results:Median age was 52 years old. All tumours were IE stage. Helicobacter pylori was positive in 15 cases. Three patients had other cancers (gastric adenocarcinoma, breast cancer, mantle lymphoma). All patients received antibiotic therapy (triple therapy in 12 cases and concomitant treatment in 7 cases) with responding residual disease in 6 cases and probable minimal residual disease in 9 cases. Second line antibiotherapy was pylera in 3 cases and levofloxacin with amoxicillin in 2 cases. Seven patients with low‐grade MALT lymphoma had radiotherapy. Four patients with high‐grade transformed lymphoma received chemotherapy. Seventeen patients are in complete remission after treatment achievement. Five and 10‐ year disease‐free survival are 100%.Summary/Conclusion:Eradication of Helicobacter pylori is the mainstay of treatment of gastric MALT lymphoma. The levocine‐amoxicillin combination with proton pump inhibitor seems to be effective as a second‐line treatment in case of non availability of the pylera. External irradiation is an effective and well‐tolerated treatment modality in case of resistance to helicobacter eradication. Immuno‐chemotherapy is indicated for diffuse lymphoma (stage III and IV) or in case of transformation into large cell lymphoma.
PB2042 CYTOMEGALOVIRUS INFECTION – A BRAKE IN PLATELET RECOVERY AFTER CHEMOTHERAPY IN ACUTE MYELOID LEUKEMIA PATIENTS
Authors: Popov V. , Balea M. , Patrinoiu O. , Georgescu D. , Dumitru I. , Iova A. , Begu M. , Dobrea C. , Arghir A. , Papuc S. , Soare D. , Abagiu A. , Madalina S. , Popescu G.A. , Bumbea H. 
Published: June 2019

Background:Cytomegalovirus (CMV) infection influence platelet recovery in bone marrow transplantation patients. Patients with CMV infection, primary, reactivated, or latent, require more platelet unit transfusions, this procedure determines increases the risk of transfusion‐related infections. In literature there are many reports regarding CMV implication in bone marrow recovery secondary transplant procedure.Aims:The association with CMV infection and slowly recovery of bone marrow secondary chemotherapy in AML was rarely reportedMethods:We report 2 cases with delay in platelet recovery after intensive chemotherapy‐ consolidation phase of acute myeloid leukaemia patients.Results:Patients male 46 years and female 55 years were diagnosed with AML 1. Diagnose was put using WHO criteria and was not identified any genetic abnormalities. We started 3+7 regimen with obtaining complete remission status. After bone marrow recovery we started consolidation phase with high doses Cytarabine 2 applications. After second application we observed delay in platelet recovery (more than 1 months). Bone marrow biopsy indicated severe aplasia. Serology for CMV infection was positive for IgG antibodies, PCR for CMV was positive indicated active CMV infection. Patients were referred to infectionist and was started antiviral treatment – Gancyclovir. During treatment patients presented increases of platelet count and absence of platelet unit transfusion, in 1 month patients had G1 trombocytopenia (improving of CTCAE grade from G4 to G1)Summary/Conclusion:The delay in bone marrow recovery after intensive chemotherapy used as treatment of acute myeloid leukemia patient represent a warning to check CMV infection presence. This attitude could avoid complications like infections or/and transfusions related.