bluuebunny/crossref_metadata_2025_split huggingface dataset:
PS1486 INTERLEUKIN‐33 IN PEDIATRIC PATIENTS WITH IMMUNE THROMBOCYTOPENIA: RELATION TO PROGNOSIS AND TREATMENT OUTCOME
Authors: Tantawy A. , Adly A. , Ismail E. 
Published: June 2019

Background:The pathogenesis of thrombocytopenia in immune thrombocytopenia (ITP) has shifted from the traditional view of increased platelet destruction mediated by autoantibodies to more complex mechanisms where both impaired platelet production and T‐cell‐mediated effects play a role. Interleukin‐33 (IL‐33) is a newly identified cytokine of the IL‐1 family. There is increasing evidence to suggest that IL‐33 is a key inflammatory mediator in a complex network of immune cells and non‐immune cells. IL‐33 signals via its ST2 receptor and is involved in several autoimmune diseases by regulating T cell immune responses.Aims:To assess the level of IL‐33 in children and adolescents with ITP and correlate it with disease severity, treatment response and outcome.Methods:Fifty young patients with ITP were compared with 40 age‐ and sex‐matched healthy controls. Patients were studied stressing on bleeding manifestations, organomegaly/lymphadenopathy and therapy. Bleeding score was calculated to each patient according to the ITP Bleeding Scale (IBLS). The studied ITP Patients were further classified into 3 subgroups: “newly diagnosed ITP” (ITP within 3 months from diagnosis), “persistent ITP” (ongoing ITP between 3 and 12 months from diagnosis), and “chronic ITP” (ITP lasting more than 12 months). ITP Patients were also classified into active ITP defined as platelet count below 100 x 109/L accompanying with or without bleeding episode or complete response (CR) which was defined as any platelet count of at least 100 × 109/L and absence of bleeding.Results:IL‐33 levels were significantly lower in ITP patients than controls (median [IQR], 150 [100 – 230] versus 210 [180–260] pg/mL; p = 0.011). Levels were also lower in chronic than newly diagnosed ITP. IL‐33 levels are lower among active ITP (median [IQR], 105 [85 – 120] pg/mL) compared with those in complete remission (median [IQR], 240 [200 – 250] pg/mL) and healthy controls (p < 0.001) while no significant difference was found among the two latter groups (p = 0.197). Patients who had splenectomy had lower IL‐33 levels than non‐splenectomized ones. Lower IL‐33 levels were found among patients with corticosteroid‐dependence and relapse (p < 0.05). No significant difference as regards IL‐33 between treated and un‐treated patients with active ITP. IL‐33 was positively correlated to platelet count at sampling (r = 0.714, p < 0.001).Summary/Conclusion:Conclusions: Alterations of IL‐33 levels in pediatric patients with ITP highlight the role of T‐cell immune response in the pathogenesis of ITP. It may be considered as a potential prognostic marker for the development of chronic ITP as it correlates with disease activity. Further studies investigating the role of IL‐33 in the pathogenesis of ITP may provide a new therapeutic target for ITP.
PS1574 HLA‐DRB1∗15 INCREASES THE RISK OF RED BLOOD CELLS ALLOANTIBODIES IN PATIENTS WITH BETA THALASSEMIA MAJOR
Authors: Mashaykhi L.A. Al , Al‐Khabori M.K. , Al‐Riyami H. , Al‐Rawahi B. , Wali Y. , Daar S. 
Published: June 2019

Background:The cornerstone of the management of Beta Thalassemia Major (B‐TM) is lifelong Red Blood Cells (RBC) transfusion. This is associated with the development of RBCs alloantibodies. Human Leukocyte Antigen (HLA) is considered a risk factor for a number of autoimmune disorders. We hypothesized that HLA impacts the rate of alloantibody formation in patients with B‐TM.Aims:To assess the impact of HLA alleles on the risk of RBC alloimmunization in patients with B‐TM.Methods:This is a retrospective cohort study of patients with B‐TM managed at Sultan Qaboos University Hospital (SQUH) between January 1996 till December 2016. All adult and paediatric patients with B‐TM with available HLA typing results were included. Patients with missing data were excluded. Chi‐squared test was used to assess the impact of HLA alleles on alloimmunization and the effect size was estimated using odd ratio (OR). HLA testing was performed using polymerase chain reaction – specific sequence of oligonucleotides (PCR‐SSO). Gel card technique (BIORAD ID‐System; DiaClon, Bio‐Rad, DiaMed GmbH, Switzerland) was used to screen for the RBC alloantibodies.Results:One hundred and sixty‐five patients fulfilled the inclusion criteria without missing information. The median age of all patients was 14 years. Females constituted 48% of the sample and 45% of patients were O RhD positive. The median RBC transfusion was 17 times per year. Patients were first detected to have RBC alloantibody at a median age of 16 years. The commonest RBC alloantibodies found in these patients were anti‐K (50%) and anti‐E (58%). The commonest HLA allele in loci A, B, C, DQ and DRB1 were HLA‐A∗02 (21%), HLA‐B∗51 (14%), HLA‐C∗7 (18%), HLA‐DQ∗05 (47%) and HLA‐DRB1∗16 (32%) respectively. HLA‐DRB1∗15 and HLA‐DQ∗6 were associated with a higher risk of RBC alloantibody formation (HLA‐DRB1∗15: OR 3.57, P = 0.047; HLA‐DQ∗06: OR 4.37, P = 0.025). None of the remaining common alleles (>5%) in Omani population were associated with the risk of alloantibody formation (p values >0.05).Summary/Conclusion:HLA‐DRB1∗15 and HLA‐DQ∗06 increases the risk of RBC alloantibody formation in patients with B‐TM. We recommend extended RBC phenotyping and extended antigen matched blood transfusion in patients carrying these two alleles. These findings will need to be confirmed in a larger multicenter study.
PS1584 A PHASE II DOSE‐FINDING STUDY OF DALTEPARIN IN CHILDREN WITH VTE WITH OR WITHOUT CANCER
Authors: Hartman L. , Nurmeev I. , Svirin P. , Sherman N. , Wolter K. , Yan J.L. , Jani D. , Goldenberg N. 
Published: June 2019

Background:Venous thromboembolism (VTE) is an important clinical concern in children with or without cancer. Experience with dalteparin, a low molecular weight heparin, in the treatment of VTE in adults with cancer has been extensively published, but data in children are limited.Aims:We sought to determine the twice‐daily dalteparin dose required to achieve target Anti‐Xa levels of 0.5–1.0 IU/mL, as well as its pharmacodynamics (PD), efficacy, and safety in the treatment of VTE in children <19 years old, with or without cancer.Methods:This prospective, multi‐center, Phase 2, open‐label study consisted of 3 phases: 1) Dose Adjustment Phase of up to 7 days, in which Anti‐Xa levels were measured following the first, second or third dose of dalteparin, until achievement of the target level; 2) PD Phase of up to 7 days, to obtain 2 randomized PD plasma samples for Anti‐Xa determination; and 3) Follow‐Up Phase, to complete up to 90 days of anticoagulant therapy. Patients were assessed for symptomatic new or progressive (i.e., recurrent) VTE as well as clinically relevant bleeding during treatment. Surveillance VTE imaging was performed at 90 ± 14 days.Results:The safety population consisted of 38 patients who received at least 1 dose of dalteparin (<2 years: n = 3; ≥2 to <8 years: n = 8; ≥8 to <12 years, n = 7; ≥12 to <19 years: n = 20). Twenty‐six patients (68%) had a diagnosis of cancer at baseline, of which 23 (88%) were haematological malignancies. The median [range] dalteparin dose required to achieve target Anti‐Xa levels decreased with age (<2 years: 207.5 IU/kg [201.5–213.5 IU/kg]; ≥2 to <8 years: 128.15 IU/kg [123.9–180.3 IU/kg]; ≥8 to <12 years: 125 IU/kg [124.5–152.6 IU/kg]; ≥12 to <19 years: 116.7 IU/kg [99.1–159 IU/kg]) (Figure). Therapeutic Anti‐Xa levels were achieved in 90% of patients within a mean (SD) of 2.6 days (1.54 days); the mean (SD) number of dose adjustments per patient was 0.7 (0.98). One patient (3%) developed symptomatic recurrent VTE. No patients reported clinically‐relevant bleeding. Four patients (11%) had treatment‐related serious adverse events. 62% of patients had complete resolution of their VTE at the end of the 90‐day reporting period.Summary/Conclusion:Twice‐daily dalteparin dosing achieved therapeutic levels in 90% of children with or without cancer, with a satisfactory tolerability profile. The median therapeutic doses of dalteparin were higher for the two youngest age cohort groups (<2 years and 2 to <8 years).imageNCT00952380Sources of Research Support: This study was sponsored by Pfizer Ltd.
PS1590 CENTRAL VEIN CATHETERIZATION IN ONCOHEMATOLOGICAL PRACTICE: RISK OF COMPLICATIONS
Authors: Romanenko N. , Schmidt A. , Glazanova T. , Shilova E. , Chebotkevich V. , Voloshin S. 
Published: June 2019

Background:The insertion of the central venous catheter (CVC) is a vascular access method used in resuscitation and oncohematology and it is required during intensive infusion and chemotherapy. However, due to the invasiveness of the procedure, complications are possible due to the procedure and course of the underlying disease.Aims:Assess the frequency of complications related to central vein catheterization in patients with hematology malignancies (HM).Methods:We have analyzed 2506 cases of CVC performed to patients with HM for the period from 2003 to 2018. All patients underwent catheterization of the right (82%), left (17.6%) subclavian vein or v. Jugularis externa (0.4%). Bacteriology tests were performed if a catheter‐related infection was suspected (n = 353).Results:Out of 2506 catheterizations bloodstream infections in the form of sepsis or bacteremia were documented in 2.5% of patients (n = 63), phlebitis, thrombophlebitis and infiltrate at CVC area were revealed in 2.6% (n = 66), lymphorrhea – in 1.3% (n = 33), catheter bleeding – in 3.9% (n = 73), haematoma – in 4.3% (n = 109), artery puncture (a. Subclavia dextra or sinistra) – in 3.0% (n = 76), pain, numbness, paresthesia of the upper limb – in 1.6% (n = 41), weakness, collapse – in 1.1% (n = 27), pneumothorax – in 0.2% of patients(n = 4). Positive bacterial cultures from venous blood were detected in 63 patients, with mixed infection in 8 cases (2 or 3 microorganisms). Detailed analysis of the infectious pathogens have demonstrated the prevalence of coagulase‐negative staphylococcus (Staph. epidermidis) – 56.3% (n = 40), At the same time, a relatively large percentage was represented by Staphylococcus aureus – 5.7% (n = 4), Micrococcus spp. – 1.4% (n = 1), Enterococcus spp. – 1.4% (n = 1). Gram‐negative microorganisms were detected in 26.7% (n = 19) of cases: Escherichia coli – 14.1% (n = 10) patients, Enterobacter spp. – 5.6% (n = 4), Enterobacter aerogenes – 1.4% (n = 1), Acinetobacter spp. – 1.4% (n = 1), Pseudomonas aeruginosa – 1.4% (n = 1), Neisseria spp. – 2.8% (n = 2). Causative agents of fungal infections were found for 8.5% of patients (n = 6), including fungi of the genus Candida – 7.1% (C. albicans (n = 4), C. crusei (n = 1), Rhodotorula spp. – 1.4% (n = 1).Summary/Conclusion:In patients with HM among catheter‐associated infections, coagulase‐negative staphylococcal infection (Staph. epidermidis) is most prevalent, which is most likely due to contact route of infection.
S1603 FIRST CLINICAL (PHASE 1B/2A) STUDY OF IBERDOMIDE (CC‐220; IBER), A CELMOD, IN COMBINATION WITH DEXAMETHASONE IN PATIENTS WITH RELAPSED/REFRACTORY MULTIPLE MYELOMA
Authors: Lonial S. , van de Donk N.W. , Popat R. , Zonder J.A. , Minnema M.C. , Larsen J.T. , Nguyen T.V. , Chen M.S. , Bensmaine A. , Biyukov T. , Sonneveld P. 
Published: June 2019

Background:IBER is a novel cereblon E3 ligase modulator (CELMoD) with enhanced tumoricidal and immunostimulatory activities. Preclinically, IBER overcomes immunomodulatory drug (IMiD) resistance and has synergy with daratumumab (DARA), bortezomib (BORT), and dexamethasone (DEX).Aims:This phase 1b/2a multicenter, open‐label, dose‐escalation study (NCT02773030) was conducted to evaluate the maximum tolerated dose (MTD), recommended phase 2 dose (RP2D), safety and preliminary efficacy of IBER in combination with DEX, in patients with relapsed/refractory multiple myeloma (RRMM).Methods:Eligible patients had RRMM and must have received ≥2 prior regimens including lenalidomide (LEN) and/or pomalidomide (POM), and a proteasome inhibitor (PI). All patients had progressed on or within 60 days of last MM therapy. Escalating doses of IBER were given on days 1–21, in combination with DEX 40 mg (20 mg in patients aged >75 years) on days 1, 8, 15, and 22, of each 28‐day cycle. Dose escalation was reviewed by a dose escalation committee.Results:As of January 2019, 58 patients had received IBER + DEX. Median age was 64.5 years (range 33–79), and median number of prior regimens was 5 (2–12). Prior therapies included autologous stem cell transplantation (79%), LEN (100%), POM (69%), PIs (100%), and DARA (66%). IBER dose ranged from 0.3 to 1.2 mg; MTD/RP2D was not reached. Median duration of therapy was 12+ weeks (range 4–109). Grade 3–4 adverse events (AEs) were reported in 41 (72%) patients and were not related to dose. Grade 3–4 neutropenia, thrombocytopenia, neuropathy, and fatigue occurred in 26%, 11%, 2%, and 0% patients, respectively. Three patients discontinued treatment due to AEs. Clinical activity occurred early and was observed across all dose levels (Table 1); 20 of 51 patients remain on treatment (2–27+ cycles).Summary/Conclusion:IBER + DEX showed favorable efficacy and safety in heavily pretreated patients with RRMM who failed multiple prior therapies. This study is ongoing, including combinations of IBER with DARA or BORT.image
PB1688 SUCCESSFUL HAPLOIDENTIC BONE MARROW TRANSPLANTATION WITH INOTUZUMAB OZOGAMICIN IN PATIENT WITH RELAPSED AND RESISTANT B CELL ACUTE LYMPHOBLASTIC LEUKEMIA
Authors: Ünal A. , Çelik S. , Güven Z. T. , Eser B. , Kaynar L. , Çetin M. 
Published: June 2019

Background:Although chemotherapeutic(CT) agents that used in the treatment of acute lymphoblastic leukemia(ALL) increase survival, the results are still weak. Long‐term survival with CT's in relapse ALL cases is difficult and the prognosis is very weak. Inotuzumab ozogamicin is an anti‐CD 22 monoclonal antibody and it has the potential to reduce the overall toxicity of intensive regimens for ALL, as well as to possibly increase the number of patients who may achieve a state of minimal residual disease.Aims:We aimed to present a case of successful haploidentic bone marrow transplantation in a recurrent B‐ALL patient who was in remission with inotuzumab ozogamicin.Methods:Case description: 26‐year‐old male patient was diagnosed with B‐cell ALL in December 2017. After the HOELZER CT protocol was started, maintenance treatment was continued.In the fifth month of treatment,FLAG CT protocol was started cause of recurrence was seen on 5% blast detection in peripheral blood smear. In August 2018, inotuzumab ozogamicin treatment was started and six cures were completed because the patient was not in remission. In September 2018, He had gone Haploidentical bone marrow transplantation from his sibling donor(8/10) with Defibrotid prophylaxis for Veno‐Occlusive Disease(VOD)s. He engrafted succesfully and chimerizm was 99.85% in 30th days of transplantation. He is 60th day of transplantation and in a remission.Results:Bone marrow transplantation cannot be performed since the complete response cannot be achieved in patients with relapse and resistant B‐ALL. In these patients, new therapies targeting malignant lymphoblasts are needed. Inotuzumab ozogamicinis a monoclonal antibody drug conjugate that targets CD22 antigen on malignant lymphoblasts.In many studies, it has been shown that Inotuzumab ozogamycin is effective and reliable anti‐tumor activity in adults with recurrent and resistant CD22 positive ALL. However, monoclonal antibody drug conjugates have been shown to be associated with VOD's. For this purpose, we used Defibrotid to protect our patient from VOD.Summary/Conclusion:Treatment with combination CT regimens in B‐ALL is suboptimal and long‐term survival is achieved in only 30‐40% of patients. Targeted molecular therapy and new regimens are needed in relapse and resistant patients. At this point, Inotuzumab ozogamycin is an anti‐CD‐22 monoclonal antibody, as in our case, it provides remission in recurrent and resistant B‐ALL patients and allows patients to complete their treatment with an allogeneic transplant from a fully compatible donor.
PB1705 CBC PARAMETERS BASED DERIVED PREDICTIVE FACTOR FOR ACUTE PROMYELOCYTE LEUKEMIA
Authors: Haider R.Z.H. , Buoro S. , Simon‐Lopez R. , De Paula E. , Shamsi T.S. 
Published: June 2019

Background:Acute promyelocytic leukemia (APML) due to coagulopathies drives hematological distress in clinical practices. A targeted and timely offered treatment can be a benefitting tool for patients.Aims:Present study was conducted to introduce pre‐microscopic screening of patients with acute promyelocytic leukemia (APML) through research potential parameters generated by routine hematology analyzers during CBC analysis.Methods:Blood samples of controls and patients (APML and other hematological neoplasms) were analyzed on Sysmex XN‐1000. Peripheral blood film was examined for morphological diagnosis. CBC parameters and values for intensities of white blood cell's side, forward, and side florescence light scatter were recorded from analyzer software. Statistical and machine learning (unsupervised) tools were used to evaluate the predictive power of routine and research CBC parameters. Novel APML factor was derived from white blood cell and platelet count along mean value of neutrophil side fluorescence light (NE‐SFL) through logistic regression. At proposed cutoff value (‐2.011), APML factor was challenged for prediction of APML among present study cases.Results:Values for white blood cell (WBC), platelet, and NE‐SFL were exceptionally discriminative for APML 5.65, 29.5, and 54.4 respectively in comparison to non‐APML 7.96, 219, and 47.00 respectively cases. In combination, WBC and platelet count increased the predictive power of NE‐SFL when utilized in derivation of our proposed “APML factor”: ‐4.5070 + (0.049213 x NE‐SFL) + (‐0.017431 x PLT) + (‐0.0058366 x WBC). This factor gave robust impact in differentiation of APML with high values 0.935 and 0.985 for sensitivity and negative predictive power (NPP) respectively at cutoff of ‐2.011.Summary/Conclusion:Our proposed APML factor has strong potential to be incorporate/calculate and examine as part of CBC report for early prediction of APML.
PB1742 AGE, KARYOTYPES AND WHETHER RECEIVING INDUCTION CHEMOTHERAPY ARE INDEPENDENT PROGNOSTIC FACTORS IN ELDERLY PATIENTS WITH AML
Authors: Wang W. , Jiang Z. , Ma J. , Sun H. , Sun L. , Meng X. 
Published: June 2019

Background:Acute myeloid leukemia (AML) is an aggressive disease with an unfavorable prognosis. AML is more common in elderly patients, and the treatments for these patients are limited, particularly for those with poor performance status, comorbidities, and unfavorable cytogenetic abnormalities. There are no universally accepted, standard approaches to treat AML in elderly patients.Aims:To analyze the clinical characteristics and prognostic factors of elderly patients with acute myeloid leukemia(AML).Methods:A total of 232 AML patients were enrolled in this retrospective study.The clinical characteristics were collected and analyzed retrospectively. Factors affecting complete remission (CR) were analyzed by using chi square test. Univariateand multivariate analyses of prognostic factors were performed by using Kaplan‐Meier and Cox hazard regression model respectively.Results:195 of 232 patients received induction chemotherapy, among whom 8 patiens died in early phase. 162 patients were able to be evaluated the efficacy, the CR rate after the first circle was 37.0 % (60/162). Overall CR rate was 54.9% (60/162). 37 patiens received palliative treatment, among whom 6 patients died in early phase and none achieved CR. Age between 60‐69 (χ2=4.102, P = 0.043), ECOG score≤2 (χ2=9.917, P = 0.002), NPM1+FLT3‐ITD‐ (χ2=6.423, P = 0.038), favorable karyotypes (χ2=6.033, P = 0.049) were related to a higher CR rate. The median overall survival (OS) was 205 day. Univariate analysis results demonstrated that age≥70 years (χ2=8.7, P = 0.003), white cell count≥100 × 109/L (χ2=4.249, P = 0.039), unfavorable karyotypes (χ2=4.807, P = 0.028), palliative treatment (χ2 = 191.221, P = 0.000) were influence factors on OS. In multivariable analysis, age between 60‐69 (HR = 0.464,95 % CI 0.245∼0.877,P = 0.018), unfavorable karyotypes (HR = 3.618,95 % CI1.491∼6.728,P = 0.003) and receiving induction chemotherapy (HR = 0.076,95 % CI 0.030∼0.194,P = 0.000) were independent prognostic factors for OS in elderly patients with AML.Summary/Conclusion:The prognosis of elderly patients with AML is the result of the combined effect of many factors. Age, karyotypes and whether receiving induction chemotherapy are independent prognostic factors in elderly patients with AML.
PB1758 CHILDHOOD ACUTE MYELOID LEUKEMIA IN SOUTHERN TUNISIA: ABOUT 52 CASES
Authors: kassar O. , mallek R. , Fakhfakh Y. , charfi M. , chaari M. , kallel F. , ghorbel M. , frikha I. , belaaj H. , mdhaffar M. , mseddi S. , Elloumi M. 
Published: June 2019

Background:Childhood acute myeloid leukemia (AML) represents 20% of childhood acute leukemia. Despite major improvement in outcome, the prognostic is pejorative compared with childhood acute lymphoblastic leukemia.Aims:We report the clinical features and treatment outcome of children de novo AML in southern Tunisia.Methods:Our study is retrospective including Children (age ≤ 20 years) affected by de novo AML between January 2005 and June 2018 treated in the department of hematology of CHU Hedi Chaker Sfax. Diagnosis has been established according to FAB classification confirmed by flow cytometry. Secondary leukemia and FAB M3 were excluded. Induction chemotherapy associated cytarabine 200 mg/m2 for 7 days and daunorubicin 60 mg/m2 for 3 days or mitoxantrone 12 mg/m2 for 5 days. After induction, patients with an HLA‐matched sibling donor underwent allogeneic Bone Marrow Transplantation (allo‐BMT) in first complete remission (CR1). Patients without a matched sibling donor received in CR1 three or four courses of consolidation. We evaluated complete remission rate, overall survival (OS) and event‐free survival (EFS). The Kaplan‐Meier method was used to estimate OS and EFS.Results:We collected 52 cases of childhood AML, including 28 boys and 24 girls (sex ratio = 1.03). The median age at diagnosis was 12 years (1.5‐20 years). The median initial white blood cell and hemoglobin level were 76 G/L (extreme 0.9 G/L ‐ 900 G/L) and 6.5 g / dL respectively. The median count of platelet was 55000/mm3. Distribution according FAB classification was: 17% of AML0, 21% of AML1, 19% of AML2, 23% of AML4, 6%of AML5 and 2% of AML6, 6% of AML7 and 2% of AMLbipheno. Cytogenetic of bone marrow cells showed chromosomal abnormalities in 58% of cases, only 13 (25%) patients had favorable abnormalities. Thirty‐one patients (60%) achieved complete response after one cure and 34 patients (65 %) after one or two courses of chemotherapy. Failure rate and toxic death were respectively 8% and 27%. Hematopoietic stem cell transplant was indicated in 24 (46%) patients but only 8 underwent the procedure. Nine patients (17.3%) relapsed within 8 months from diagnosis. The 5‐year OS and EFS were 50% and 48% respectively.Summary/Conclusion:Our study is characterized by frequent leucocytosis forms and FAB type M2. The CR rate and our EFS and OS rates observed in our series remain lower than in international trials. These can be explained by the frequency of refractory forms and the small number of bone marrow transplantation. Intensification chemotherapy of induction as well as consolidation therapy with allo‐BMT can improve the outcome of our patients.