bluuebunny/crossref_metadata_2025_split huggingface dataset:
PB1831 PRELIMINARY RESULTS OF THE COMBINED TREATMENT PRIMARY NON‐HODGKIN ORBITAL LYMPHOMAS
Authors: Jazyltayeva A. , Jazyltayeva A. , Gabbasova S. , Karakulov R. , Kemelbekov N. , Sagyndikov G. , Nassipov B. , Akanov A. , Taktybayeva A. 
Published: June 2019

Background:Non‐Hodgkin Lymphomas (NHL) effected organ of vision compose 8–12 % of all primary extranodal NHL, and may be the first and only sign of the disease.Aims:To estimate a therapy of patients with extranodal orbital lesion in our cancer center.Methods:Since 2014 to 2018 in our center treated 17 patients with extranodal damage to the orbit of the eyes. The age of patients ranged from 23 to 92 years, the average age of patients was 57 years. The number of men were 8 people, women ‐ 9. Unilateral orbital damage was registered in 15 patients, bilaterally in 2 patients. In 12 cases process localized in the anterior part of the orbit, in 5 ‐ in the middle and deep parts of the orbit with the spread in the maxillary sinus. Clinical sings of NHL characterized with exophthalmos in varying degrees of severity, difficult reposition, displacement of the eyeball and restriction of its mobility, swelling of the eyelid. By all the observations: to 12 patients performed biopsy of the tumor, 4 patients underwent therapeutic and diagnostic orbitotomy by Killian, to 1 patient ‐ eye orbit exentation. Histological variants: MALT‐ lymphomas – 4 patients, Diffuse B‐cell Lymphoma – 8, Mantle Cell Lymphoma – 2 and Follicular Lymphoma ‐ 2 patients.Results:All patients underwent 6 courses of chemotherapy according to the R‐EPOCH protocol. Complete answer registered in 16 cases, partial answer in 1 of cases, and this patient received a course of radiation therapy on the affected area. Observation median was 3 years (15 month‐5 years).Summary/Conclusion:Therefore, treating orbital NHL requires complex multidisciplinary approach, allowing determining the correct diagnosis and prescribing adequate treatment. Standart first line therapy achieved good results of relapse‐free survival. Chemotherapy showed the same results as the combined treatment (chemotherapy and orbitotomy).
PB1839 SUCCESSFUL PERIOPERATIVE HEMOSTATIC MANAGEMENT FOR SURGERY IN PATIENTS WITH CONGENITAL FACTOR IX DEFICIENCY: A SINGLE CENTER EXPERIENCE
Authors: Park Y.S. 
Published: June 2019

Background:Hemophilia B is an X‐linked recessive bleeding disorder resulting from factor IX (FIX) deficiency. Prevalence of hemophilia B is one in 20,000 live male births, a quarter that of hemophilia A. While coagulation factor replacement is essential in surgical intervention in hemophilia B patients, evidence in support of the perioperative management is more lacking than hemophilia A.Aims:This study provides an updated evaluation of the safety and effectiveness of coagulation FIX concentrates in treating perioperative bleeding.Methods:We reviewed the records of hemophilia B patients without inhibitors who underwent surgery between June 2006 and May 2017 using coagulation FIX concentrates at a single center. The first bolus of [80 IU/kg X 1.2‐1.4] was given 30 min before surgery to achieve a preoperative FIX level of 80 % under the supervision of a multidisciplinary hemophilia team of our institute. Approximately 50% of the initial dose was administered every 12 h and the dosing intervals were increased to 24 h.Results:In total, 109 surgeries (93 orthopedic, 16 other) were conducted in 70 hemophilia B patients. The median age of the patients was 35.5 years (range, 6–78). The median duration of hospitalization was 14.3 days (range, 2–47), and median duration from operation to discharge was 11.5 days (1‐42). Recombinant FIX concentrates were administered in all cases except 2 patients. The major surgical procedures, that were defined as one that required hemostatic support for periods exceeding 5 consecutive days, were 94 cases (89.5%). Median difference between preoperative and postoperative hemoglobin was 2.35 g/dL (range, 0‐7.7). Total 18 cases of patients required packed RBC transfusion after surgery. In most cases, bleeding stopped or was well controlled; however, one patient expired after emergent surgery for intracranial hemorrhage. No thromboembolic event and development of antibody to FIX were observed in any case.Summary/Conclusion:Good control of hemostasis can be achieved using FIX concentrates in hemophilia B patients who are undergoing surgery. Thorough planning is needed before elective surgery and more active and aggressive management may be needed for emergency surgery.
PB1843 EFFECT OF ADHERENCE TO PHYSICAL THERPY REGIMEN ON JOINTS OUTCOMES FOR HEMOPHILIAC CHILDREN AT ZAGAZIG UNIVERSITY HOSPITALS
Authors: Hesham M. , El‐Dakhakhny A. , Hanfy M. , Abo‐Elsoaud A. 
Published: June 2019

Background:The maintenance of healthy joints and muscles is crucial to the quality of life of patients with hemophilia. Clotting factor replacement may stop or even prevent bleeds but it does not restore joint or muscle function. Only regular movement and exercise and adherence to them can do that. Physiotherapy aims to bring relief from pain, restore muscle power and control, restore range of joint movement and prevent further injury to a target joint. Enhancing adherence, joint function and decreasing pain by using physiotherapy is the major hope for all hemophiliac patients, especially in developing countries with limited access to treatment.Aims:to Identify the effect of adherence to physical therapy regimen on joint outcomes for children with hemophilia.Methods:A quasi–experimental study was conducted on a sample of “35” children were suffering from hemophilia “A” or “B” at the Pediatric Hematology outpatient clinic at Zagazig University Hospitals. The knee joint was selected to perform the physiotherapy regimen Tools was composed of three parts Part I: a structured interview sheet. Part II assessment of adherence using (attendance at clinic appointments, SIRASa and Patient Self‐Report Scale of their Home‐Based Rehbiltation adherence). Part III was the assessment of the musculoskeletal status and joint evaluation using (Gibert score, FISH© and the musculoskeletal data sheet).Results:‐ There was a significant statistical relation and improvement in the mean score of functional ability of the studied group throughout the intermediate and post‐test phases than the pre‐test phase.‐ There was a significant statistical improvement in the studied sample adherence and knee joint outcomes throughout the study phases.Summary/Conclusion:the adherence to physiotherapy have a profound effect on improving joint outcomes. So,we recommend encouraging the awareness of hemophiliac patients about physiotherapy and its beneficial role in decreasing the musculoskeletal complications.
PB1847 CONGENITAL COMBINED DEFECTS OF COAGULATION FACTORS FVII AND FX: ABOUT A TUNISIAN FAMILY.
Authors: Maalej S. , Megdiche F. , Ghorbel M. , Kacem S. , Kassar O. , Fakhfakh Y. , Kotti F. , Chaabane H. , Mbarek L. , Elloumi M. , Kallel C. 
Published: June 2019

Background:Combined factor VII (FVII) and factor X (FX) deficiency is considered as an extremely rare bleeding disorder. Only a few cases have been reported all over the world. According to the WFH (World Federation of Hemophilia) 2014, the global populations’ prevalence of combined defects of coagulation factors (CDCF) is close to 1:2 000 000. These recessively inherited coagulation disorders, are usually associated with a high consanguinity's rate. Unfortunately, diagnosis is still underestimated, mainly due to the important heterogeneity of clinical and biological phenotypes which may induce difficulties in the disease's management in patients.Aims:The aim of this study was to report two cases presenting a combined FVII‐FX deficiency diagnosed in the South of Tunisia.Methods:Biological investigation included prothrombin time (PT), activated partial thromboplastin time, FVII and FX analysis by coagulometric methods and fibrinogen by the Clauss method.Results:An 11‐year‐old female was referred to our laboratory to realize routine screening tests before a tonsillectomy. Haemostasis has been checked and results showed a prolonged PT (PT = 45%, normal range:70‐100%) (aPTT and fibrinogen were normal), which prompted to realize further tests. Our patient, offspring of a consanguineous marriage, reported, since an early age, recurrent epistaxis and abundant gingivorrhagia. Laboratory analyses showed a combined FVII and FX deficiency with a mild decrease of both FVII and FX coagulant activities as follows: (FVII:C = 52%, normal range: 55‐170%) and FX:C = 36%, normal range: 70‐120%) which required a family screening. It was then revealed that she had an older sister (17 years old) with a combined FVII and FX deficiency (FVII:C = 53%, FX:C = 47%). Clinically, the sister presented gingivorrhagia since an early age. With regard to the parents, the plasma levels of the father revealed that he was probably a carrier of FX deficiency (FX:C = 51%) and he complained about gingivorrhagia and epistaxis too. However, the mother and two other sisters had normal coagulant activities and didn’t suffer from any abnormal bleeding disorder.Summary/Conclusion:In accordance with the recent reports, the presence of two clotting defects in a patient may cause diagnostic difficulties. For that, firstly, an acquired vitamin K deficiency should be excluded by getting normal clotting activities of both factors II and IX. Secondly, to avoid a misdiagnosis, it's recommended to investigate both FVII and FX in cases with prolonged PT, especially that patients belonging to the South of Tunisia are known by high rates of consanguineous marriages. Added to that, it's important to explore the mutational spectrum of F7 and F10 and its associated phenotypes in order to attest the combined defects and to guarantee a better genetic counselling.
PB1860 A TURKISH CHILD PRESENTED WITH NEONATAL THROMBOCYTOPENIA ASSOCIATED WITH GNE MUTATION WITHOUT ASSOCIATED MUSCLE WASTING
Authors: Yilmaz E. , Ozcan A. , Verboon J.M. , Karakukcu M. , Sankaran V.G. , Unal E. , Patıroglu T. 
Published: June 2019

Background:Mutations in the glucosamine (UDP‐N‐acetyl)‐2‐epimerase/N‐acetyl mannosamine kinase (GNE) gene have previously reported in children with myopathy, however, recently GNE gene mutations were reported to be causative in nine children with thrombocytopenia without associated muscle wasting.Aims:Here we share our experience of a child with macrothrombocytopenia without muscle wasting associated with GNE.Methods:The clinical and genetic features of child with GNE is reportedResults:A 30‐day‐old male was referred to Pediatric Hematology Clinic of Erciyes University with complaints of generalized petechial rash, ecchymoses just after birth and it was learned that he received intravenous immunoglobulin and platelet transfusions due to suspected neonatal allo‐immune thrombocytopenia at another medical center. His parents were first cousins. He was referred to our hospital NICU with thrombocytopenia. Blood count analyses revealed a hemoglobin of 10.6 g/dL, leukocyte count of 7810 x109/L, and platelet count of 6 x109 /L. The blood smear showed giant platelets. The bone marrow aspiration showed mild granulocyte maturation. He developed severe transfusion depended mucosal bleedings due to severe thrombocytopenia and neutropenia, so hematopoietic stem cell transplantation was planned. As no matching donor was found from the family or unrelated family, alpha beta depleted haploidentical hematopoietic stem cell transplantation (HSCT) from his father was performed. Although myeloid and platelet engraftments were achieved at +14, +13 days consequently, the chimerism decreased and the patient underwent a second haploidentical HSCT with mesenchymal stem cell support. Nevertheless, the chimerism did not improve and the patient died despite supportive treatment. Using whole exome sequencing, we identified a predicted pathogenic missense variant in the GNE gene (chr9:36219976:C>T, p.590:Gly>Arg) present in the heterozygous state in both parents and homozygous in the affected child.Summary/Conclusion:GNE mutations must be kept in mind for children with macrothrombocytopenia. Although our experience is limited, we speculate that there may be some underlying bone marrow micro‐environmental problem that resulted in early rejection after HSCT.
PB1865 SINUS BRADYCARDIA AS A SIGN OF CENTRAL NERVOUS SYSTEM INVOLVEMENT IN A CHILD WITH GRISCELLI SYNDROME TYPE 2
Authors: Kilic O. , Ay Tuncel D. , Gorkem B.S. , Ozcan A. , Akyol S. , Yuregir O.O. , Pamukcu O. , Unal E. , Karakukcu M. , Patıroglu T. 
Published: June 2019

Background:Hemophagocytic syndrome is often fatal in Griscelli syndrome type 2, and the only cure is hematopoietic stem cell transplantation.Aims:We aimed to emphasize the importance of sinus Bradycardia as a sign of Central Nervous System Involvement in a Child with Griscelli Syndrome Type 2Methods:A 6‐year‐old female Syrian refugee with gray hair was referred to Erciyes University for hematopoietic stem cell transplantation (HSCT) for Griscelli syndrome type 2. Her parents were consanguineous, and one of her siblings had the similar hair color and died when she was 9 months old.Blood count analyses revealed a hemoglobin of 5 gr/dl, leukocyte count of 810x109/L and platelet count of 2x109/L. Bone marrow aspiration and biopsy showed hemophagocytosis with normal cellularity. Sinus bradycardia was detected on the first day of her admission on ECG (50/min). Because of sinus bradycardia, a cranial magnetic resonance imaging (MRI) was done. A homozygous pathogenic c.514_518delCAAGC (p.Gln172Asnfs∗2) (pQ172Nfs∗2) variant was detected in the molecular analysis of RAB27A gene.Results:After the diagnosis of Griscelli syndrome type 2, she was treated according to the HLH 2004 protocol with additional intrathecal chemotherapy. The bradycardia recovered in three days. Six weeks after this treatment the patient showed complete improvement but her parents refused further treatments.Summary/Conclusion:Different types of arrhythmia can be seen in different types of diseases that may affect the CNS. According to best of our knowledge, this is the first reported case of a child with Griscelli syndrome type 2 who presented sinus bradycardia as a sign of CNS involvement. It should be considered that sinus bradycardia in a child with partial oculocutaneous albinism may be an important predictor for CNS involvement of GS‐2.
PB1866 SUCCESSFUL MANAGEMENT OF A CHILD FOR PAROXYSMAL NOCTURNAL HEMOGLOBINURIA WITH LONG‐TERM ECULIZUMAB THERAPY
Authors: Aydogan G. , Salcioglu Z. , Akici F. , Yilmaz E. , Tahtakesen T.N. , Bayram N. , Ozdemir N. 
Published: June 2019

Background:PNH arises from a genetic mutation of hematopoietic stem cells which leads to the acquired nonmalignant clonal expansion of cells lacking glycosyl phosphatidylinositol‐anchored proteins (GPI‐APs). Lack of GPI‐APs translates into PNH's most significant clinical features: bone marrow failure, intravascular hemolysis and thrombosis. PNH rarely occurs in children and has been reported to have a distinct clinical presentation compared to the adult population. Most of the pediatric patients in the litearture have arisen in a previous setting of bone marrow failure. There are few pediatric case reports presented with reccurrent hemolytic episodes.Aims:There is a paucity of published data on outcomes in children with PNH treated with eculizumab. Therefore, we find it significant to share our experience regarding the use of eculizumab for a pediatric patient, who was diagnosed as PNH at 5.5 years of age and have been managed successful by eculizumab for more than 9 years at Kanuni Sultan Süleyman Education and Research Hospital.Methods:The case is retrospectively evaluated.Results:The patient was diagnosed in March 2008 with immunphenotyping and verified with FLAER method. She had been given blood transfusions, hyperhydration therapy, low‐dose oral prednisolone continuously initially and then during hemolytic attacks. During follow‐up, attacks had become more frequent and recurred at 2‐3 weeks intervals. With the informed consent of the family, eculizumab therapy was commenced in December 2011. She was 9 year old at this time.The dose of eculizumab was set according to the weight of the child as 600 mg/week for 4 week, then 900 mg/every other week parenterally. After introduction of eculizumab, both the frequency and the severity of the attacks had declined significantly. She has been under eculizumab therapy for more than 9 years without any considerable advers effect. Reoccurence of hemolytic attack was observed, when the patient had infections or the treatment was interrupted due to problems in obtining drugs.Summary/Conclusion:Depending on our experience, eculizumab may have a substantial role in controlling hemolytic episodes and preventing thrombotic complications and improving quality of life in children similiar to adults.
PB1870 IBRUTINIB PLUS VENETOCLAX SYNERGISTICALLY REDUCES SIGNALING AND VIABILITY IN CLL: IMPLICATIONS FOR BIOMARKER DISCOVERY
Authors: Skånland S.S. , Cremaschi A. , Bendiksen H. , Hermansen J.U. , Raj D.B.T.G. , Munthe L.A. , Tjønnfjord G.E. , Taskén K. 
Published: June 2019

Background:Recently, several small molecule drugs have been approved for the treatment of chronic lymphocytic leukemia (CLL). These drugs have significantly improved the management of this patient group. However, knowledge about how to combine the novel therapies for optimal effects and what patients will best benefit from them is still lacking.Aims:The aims of this study were to investigate whether drug synergies can be identified by single cell signaling analyses, and to identify potential signaling biomarkers for response to therapy.Methods:We investigated the effects of idelalisib, ibrutinib and venetoclax on 35 protein epitopes by phospho flow cytometry in CLL patient samples. Cell viability was monitored with internal markers for apoptosis in the phospho flow assays and with independent drug sensitivity screens.Results:The activity of proteins in the B cell receptor signalosome and the phosphatidylinositol 3‐kinase pathway were altered upon drug exposure. Combined treatment with ibrutinib and venetoclax give promising results in clinical studies and we show that this combination exerted synergistic inhibitory effects both on cell signaling (Figure 1a) and on cell viability (Figure 1a, b). Our analyses indicate that the standard dosages of ibrutinib and venetoclax can be lowered without loss of efficacy, potentially reducing drug costs and toxicities. Observed correlation between cell signaling and cell viability indicates that signaling molecules could serve as biomarkers to predict response to therapy.Summary/Conclusion:We suggest that phospho flow should be considered as a novel approach for dose and synergy prediction in a precision medicine setting for CLL.image
PB1897 MANAGEMENT OF AUTOIMMUNE CYTOPENIA COMPLICATING CHRONIC LYMPHOCYTIC LEUKEMIA
Authors: Vyhovska O. , Yevstakhevych Y. , Maslyak Z. , Yevstakhevych I. , Pelenyo N. , Semerak M. , Vyhovska Y. 
Published: June 2019

Background:Chronic lymphocytic leukemia (CLL) in 4.3‐9.7% of patients is complicated with immune cytopenia (IC). Timely diagnostics of IC is important, as the therapeutic tactics in patients with IC is significantly different from standards of treatment of patients with CLL without immune complications.Aims:Determination of the peculiarities of the course of IC in patients with CLL and assessment of different treatment regimens.Methods:Under our observation, there were 83 patients with CLL complicated with IC: 38 patients with autoimmune hemolytic anemia (AIHA), 26 patients with immune thrombocytopenia (ITP), 15 patients with Fischer‐Evans syndrome, 3 patients with partial red cell aplasia, one patient with immune neutropenia.The prognostic markers of the disease were determined: expression of CD38, ZAP70, β2 MG level, Coombs’ test, FISH analysis (del11q 22.3 and del17p 13.1). 58 patients received drug therapy (the first line ‐ steroid hormones, further: the schemes of COP, CHOP or RCOP, RCHOP or monotherapy with rituximab (rituximab at a dose of 375 mg / m2 / day, 4 injections with a weekly break), 25 patients underwent splenectomy.Results:The most severe course of the disease was observed in patients complicated with Fischer‐Evans syndrome (the median overall survival of 75 months). Insignificantly better results were observed in patients with AIHA (the median overall survival of 78 months). In patients with ITP, the median overall survival has not been achieved (observation time 12‐133 months). In case of steroid hormones use, as the first line of treatment, most patients experienced short‐term remissions.When using monotherapy with rituximab, the median progression‐free was 20 months. Conducted course therapy, based on RCOP or RCHOP regimens, was effective in 82% of patients. The median progression‐free survival has not been achieved in patients of this group (observation time 12‐57 months).The median of overall survival for CLL with ITP after splenectomy was 135.0 months, for CLL with AIHA it was 69.6 months, and for CLL complicated with Fischer‐Evans syndrome it was only 49.5 months.Summary/Conclusion:Treatment of patients with CLL complicated with immune cytopenias should be individualized:1. For patients with CLL that runs without significant enlargement of lymph nodes and spleen, low lymphocytosis, in case of occurrence of AIHA or ITP the use of monotherapy with rituximabis is optimal.2. In case of occurrence of AIHA, ITP or Fisher‐Evans syndrome in patients with CLL that runs with enlargement of lymph nodes, spleen, significant lymphocytosis, the use of R‐COP or R‐CHOP schemes, 4‐6 courses, is the most effective.3. In case of resistance to drug therapy and the presence of splenomegaly in patients with CLL, complicated with IC, splenectomy is indicated.