bluuebunny/crossref_metadata_2025 huggingface dataset:
PB1828 PRIMARY PROPHYLAXIS OF CHEMOTHERAPY‐INDUCED FEBRILE NEUTROPENIA IN ADULT PATIENTS WITH LYMPHOPROLIFERATIVE DISORDERS ‐ CLINICAL EXPERIENCE IN UNIVERSITY HOSPITAL SPLIT
Authors: Petrić M. , Vicelić Čutura L. , Blaslov V. , Miljak A. , Galušić D.
Published: June 2019

Background:

Febrile neutropenia (FN) is the development of fever in a patient with an abnormally low number of neutrophil granulocytes. It can be associated with other signs of infection and is often consequence of chemotherapy treatment. Granulocyte colony‐stimulating factors (G‐CSF) are used for prophylaxis of FN. We analyzed data of adult patients with lymphoproliferative disorders who were treated with chemotherapy regimens of high or intermediate risk for developing FN, according to guidelines of European organization for research and treatment of cancer (EORTC).

Aims:

To investigate the benefit of primary prophylaxis of chemotherapy‐induced FN in patients with lymphoproliferative disoders. To evaluate the incidence of FN following chemotherapy regimens of high or intermediate risk for developing FN.

Methods:

We analyzed medical history of all 97 adult patients (M = 55; F = 42, aged 21 – 81 (mean, 54) years) with lymphoproliferative disorders who were treated with chemotherapy regimens of high or intermediate risk for developing FN in the period from 1st November 2017 till 1st November 2018. Incidence of FN was analyzed according to type of chemotherapy regimen and administration of primary prophylaxis.

Results:

Primary prophylaxis with G‐CSF was administered to all (N = 12) patients who were treated with high risk chemotherapy regimens, in compare to only 24 (28%) patients who received intermediate risk regimens. FN was registered in total of 24 (25%) patients, of whom 20 were treated with intermediate risk regimens. Among patients who received primary prophylaxis after intermediate risk regimens, only 4 (17%) of them developed FN, in compare to 16 (26%) of patients who previously did not receive primary prophylaxis after same regimens. Incidence of FN was higher in females (N = 14) and after the first cycle of chemotherapy regimen (N = 15).

Summary/Conclusion:

Primary prophylaxis with G‐CSF reduces the risk of developing FN, so it is recommended to administer primary prophylaxis to all patients who are treated with high risk chemotherapy regimens. Primary prophylaxis in patients receiving intermediate risk regimens should be carefully considered because of the high incidence of FN in those who did not receive prophylaxis. In those circumstances, other risk factors (such as comorbidities, age of patient, history of previous infections and FN, stage of the disease and others) should be evaluated before the decision whether to administer primary prophylaxis or not. In our patients, low incidence of FN was observed in the group who received primary prophylaxis after intermediate risk regimens.
PB1842 ROLE OF THROMBOELASTOGRAPHY IN THE MONITORING OF PROPHYLACTIC TREATMENT IN PATIENTS WITH SEVERE HAEMOPHILIA A
Authors: Krasivska V. , Stasyshyn O. , Semerak M. , Tushnytskyi O.
Published: June 2019

Background:

According to many experts, during prophylactic treatment, the activity of factor VIII (FVIII) is not a sufficient predictor of the effectiveness of prevention and does not reflect the level of risk of bleeding. During monitoring of the therapy with activated partial thromboplastin time (APTTT) and FVIII activity, the cause of the discrepancy may be unaccounted content of the tissue factor, the amount and the aggregative function of the thrombocytes, which are also involved in the coagulation process. Therefore, global laboratory methods, in particular thromboelastography (TEG), are used to control therapy

Aims:

To study the role of TEG in the monitoring the prophylactic treatment of clotting factors concentrates in patients with haemophilia

Methods:

The study was performed in 9 patients with severe haemophilia A, who received prophylactic treatment by prolonged recombinant FVIII concentrate at a dose of 45 ± 5 IU/ kg two times a week. According to international recommendations all the patients were tested for incremental recovery (IR) of the administered concentrate FVIII in a dose of 60 ± 5 IU/kg during their routine visits. Pre‐ and post‐infusion coagulation tests and TEG (TEG 5000® Haemoscope Corp., Niles IL) were performed

Results:

Pre‐infusion the indicators of coagulation tests that characterized coagulation hemostasis (APTT‐72,9 sec, FVIII‐1,1%) were prolonged. 30 minutes post‐infusion the abnormal value came to the norm. The prothrombin time (PT), the fibrinogen level and quantity of platelets in the IR test did not differ from the corresponding values of healthy individuals. In TEG, the prolonged reaction time to clot formation R (21,9 sec), the time of maximum amplitude TMA (46,5 sec), the time of initial fibrin formation SP (19,1 min), the reduced rate of initial clot strengthening α‐Angel (33,0°), negative value of coagulation index CI (‐3,0) indicate a violation of the enzymatic phase of blood clotting. Post‐infusion of the calculated dose of the medication, all of the abnormal parameters returned to normal. In IR test, TEG parameters that characterize strength, quality, hemostatic capabilities, lysis of the clot and depend on the level of fibrinogen and platelets do not differ from those of healthy individuals

Summary/Conclusion:

TEG can be a reliable method for monitoring prophylactic treatment and IR in patients with hemophilia A without inhibitors in combination with coagulation tests (APTT, FVIII activity). The following parameters should be analyzed: the reaction time to clot formation R, the time of maximum amplitude TMA, initial fibrin formation SP, the rate of initial clot strengthening α‐Angel, the total coagulation potential CI
PB1850 DENTAL MANAGEMENT OF PATIENTS TAKING NOVEL ORAL ANTICOAGULANTS (NOAS): DABIGATRAN.
Authors: Kapsali A. , Papakitsos G.
Published: June 2019

Background:

A new group of oral anticoagulants with clear advantages over classic dicoumarin oral anticoagulants (warfarin and acenocoumarol) has been developed in recent years.

Aims:

Patients being treated with oral anticoagulants are at higher risk for bleeding when undergoing dental treatments.

Methods:

A literature search was conducted through April 2015 for publications in the ISI Web of Knowledge, PubMed and Cochrane Library using the keywords “dabigatran”, “new oral anticoagulants”, “bleeding” and “dental treatment”.

Results:

There is no need for regular coagulation monitoring of patients on dabigatran therapy. Whether or not to temporarily discontinue dabigatran must be assessed according to the bleeding risk involved in the dental procedure to be performed.

Summary/Conclusion:

The number of patients under treatment with new oral anticoagulants will increase in the coming years. It is essential to know about the pharmacokinetics and pharmacodynamics of new oral anticoagulants and about their interactions with other drugs. It is necessary to develop clinical guidelines for the perioperative and postoperative management of these new oral anticoagulants in oral surgical procedures and to carefully evaluate the bleeding risk of dental treatment, as well as the thrombotic risk of suppressing the new oral anticoagulant.
PB1851 PREDICAMENT OF SHORTENED PRE‐OPERATIVE EVALUATION OF UNDIAGNOSED BLEEDING DISORDERS IN SURGICAL PATIENTS IN UNDER DEVELOPED COUNTRY.
Authors: Imran T. , Altaf H.N.
Published: June 2019

Background:

Von Willebrand Disease (VWD) is a prevalent genetic bleeding disorder in Pakistan. it is a leading congenital bleeding disorder followed by Haemophilia. the significance of bleeding pattern in undiagnosed patients as evident after haemostatic challanges leads to the importance of the need to confirm bleeding disorders in emergency surgical patients.

Aims:

the aim of this retrosepctive study is to document the pattern of mortality and morbidity in undiagnosed surgical patients with various congenital bledding disorders in Pakistan

Methods:

we analyzed the bleeding pattern of VWD and Haemophilia A and B in patients who were undiagnosed at the time of surgery. this retrospective study was done at Fauji Foundation Hospital from 2012 to 2016. patients’ charts were reviewed for primary diagnosis, surgical procedures and severity of bleeding by detailed history and laboratory workup. the study was carried out after approval of institutional ethical committee.

Results:

we received 14 VWD and 7 Haemophilia patients in emergency for surgical intervention. the median age was from 3 to 22 years. there were 16 male and 5 female patients. out of 21 patients 29% had laparotomy, 10% had head surgeries, 14% post trauma thoracic intervention, 10% had cholecystectomy, 19% had dental procedures and 14% had cesarean sections. collective mortality rate was 56% because of the obsecure condition added by delay in arranging appropriate treatment line for ongoing bleeding.

Summary/Conclusion:

congenital bleeding disorders are common in Pakistan. there is lack of diagnostic facilities and recognition by health care professionals. lack of awareness about these bleeding disorders before emergency surgeries results in fatal outcomes. awareness programes must be initiated in developing countries.
PB1854 MYELOFIBROSIS DUE TO SEVERE VITAMIN D DEFICIENCY RICKETS
Authors: El Chazli Y. , Eldomiaty B. , Balbaa N. , Hassan E. , Mikhael N. , Elsayed S. , Abdelmeguid Y. , Fawzy D.
Published: June 2019

Background:

The association between severe active infantile rickets and myelofibrosis has been reported as Von Jaksch's anemia since 1937. Vitamin D deficiency rickets is a common condition in infants and children of developing countries including Egypt. Despite this fact only 26 patients with myelofibrosis due to severe vitamin D deficiency rickets have been reported in the literature worldwide and none from Egypt.

Aims:

To report cases of myelofibrosis due to severe vitamin D deficiency rickets and to highlight the importance of considering this rare condition in the differential diagnosis of hypochromic microcytic anemia with splenomegaly in infants.

Methods:

retrospective description of patients diagnosed as myelofibrosis due to severe vitamin D deficiency rickets for a 6 month period at the Alexandria University Children's Hospital. After taking informed consent from their legal guardians, patients have been subjected to history taking, clinical examination, and laboratory investigations including bone marrow biopsy (BMB).

Results:

Five patients have been included. Four males and one female, with an age ranging from 6 to 22 months at presentation. They presented with clinical signs of active rickets (wide anterior fontanel, frontal bossing, rachitic rosaries, and hypotonia). They all had an enlarged spleen by examination, confirmed by ultrasonography. Their blood picture showed a hypochromic microcytic anemia (Hb 5 to 8.6 g/dL) with normoblasts, anisopoikilocytosis, teardrops and pencil cells, thrombocytopenia (platelet count 25 to 132 x103 cell/cmm, normal in one patient) and a normal white cell count showing monocytosis and immature forms (promyelocytes, myelocytes and band cells). Their chemistry was significant for low calcium, low phosphorus and very high alkaline phosphatase (ALP 922 ‐ 4678 U/L). Bone marrow was done and showed thickened trabeculae and increased bone marrow fibrosis using reticulin stain (picture). Unfortunately, the patients presenting with a symptomatic anemia had a packed red cells transfusion. All patients have been started on therapeutic doses of Vitamin D with rapid correction of their blood counts and gradual normalization of their chemistry parameters.

Summary/Conclusion:

It is important to raise clinicians’ awareness to such a rare but yet easy to diagnose condition to avoid unnecessary transfusions and investigations and delays in treatment. The treatment of myelofibrosis due to severe vitamin D deficiency rickets is very simple and effective.

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PB1855 UPFRONT HAPLOIDENTICAL TRANSPLANT IN YOUNG SEVERE APLASTIC ANEMIA PATIENTS ‐ RESULTS OF A PILOT STUDY FROM SOUTH INDIA
Authors: Kumar K. , Subash C.
Published: June 2019

Background:

Haploidentical bone marrow transplant is one of the second line treatment option in severe aplastic anemia patients failing immunosuppressive therapy. In younger patients, allogeneic bone marrow transplant from a matched sibling donor gives more than 80% long‐term remission rates. But unfortunately, only 30% patients will have a matched sibling donor. In a middle‐income country like India, the availability and affordability of patients to an unrelated donor is limited. Most of our patients have got a single chance for treatment and many relapsed patients go into palliative care.

Aims:

Aim of the present study is to evaluate the efficacy and safety of upfront Haploidentical bone marrow transplant in less than 40 years old severe aplastic anemia patients not having a 10/10 matched donor.

Methods:

This is a prospective non‐randomized single center study conducted during the period from January 2017 to June 2018. Eleven patients less than 40 years old underwent upfront Haploidentical bone marrow transplantation for severe aplastic anemia during the above period. Peripheral blood stem cell was used in all patients.FLU‐ATG‐PTcy was the conditioning regimen used in all patients with Cyclosporine + MMF based GVHD prophylaxis. This study got clearance from institutional review board and the transplant was sponsored by government.

Results:

In six patient's donors were parents (Mother in four and father in two) and rest of the donors were siblings. Two were Fanconi positive and none had a PNH clone. Seven were 5/10 matched, three were 6/10 and one was 7/10 matched. All patients had engraftment at a median of 11 days (range 8 to 13 days). One patient had fatal grade IV acute GVHD and succumbed to GVHD on day +36. Seven patients (64%) had grade I/II GVHD and three patients (27%) had grade III GVHD. 64% patients had grade I/II chronic GVHD at date cut off of January 2019. 10 patients (89%) attained complete remission and were alive till January 2019.The overall survival rate at one year post transplant was around 89% which is better than immuno‐supressive therapy in this age group. No differnces were observed in engraftment dates or survival outcomes based on type of donor and degree of mismatch. The study patients are very small to get statistically significant rates.

Summary/Conclusion:

With nearly 90% overall remission and survival rate at one year, upfront haploidentical transplant seems to be a safe and effective option in young patients with severe aplastic anemia. This will help to reduce the cost of Matched unrelated donor stem cells significantly in resource poor countries and increase the number of patients opting for a curative treatment.
PB1857 THE ROLE OF WHOLE‐BODY MAGNETIC RESONANCE IMAGING IN THE DETECTION OF VASCULAR EVENTS IN PATIENTS WITH PAROXYSMAL NOCTURNAL HEMOGLOBINURIA.
Authors: Navarro‐Almenzar B. , Salido Fiérrez E. , Cabañas Perianes V. , Pérez López R. , García Candel F. , Fernández Poveda E. , Blanquer Blanquer M. , Leal Rubio J.D. , Torregrosa Salas B. , Moraleda Jiménez J.M.
Published: June 2019

Background:

Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired clonal disorder characterized by intravascular hemolysis, cytopenias, and recurrent thrombosis. Thrombotic events are just the main cause of morbidity and mortality. Therefore, it is essential to detect them early to treat them and avoid sequels.

Aims:

To analyze the diagnostic value of the whole‐body magnetic resonance imaging (WB‐MRI) in the detection of symptomatic and silent vascular events.

Methods:

Retrospective study in which a 1.5 Tesla whole‐body magnetic resonance (Philips Achieva, Philips Medical Systems, Best, the Netherlands) with Gadolinium contrast was performed along 2017 and 2018 to patients diagnosed of classical PNH in Autonomous Community of the Region of Murcia, Spain. The image findings were analyzed.

Four patients were included (3 men and 1 woman) with median age of 54 years, diagnosed of either PNH (n = 2) and AA/PNH (n = 2). At the time of investigation, mean size clon in granulocytes measured by FLAER was high (90.7 %, range 75.6‐99.3 %) and mean LDH was 341.7 U/L (range 204‐465 U/L; normal range 135‐214 U/L). Only one patient had prior history of thrombosis (Budd‐Chiari syndrome). All patients were treated according to Spanish PNH guidelines, including the use of complement inhibitor Eculizumab.

Results:

WB‐MRI findings showed unknown bone infarctions in two (50%) patients (patient 1 and patient 3). In patient 1, symptomatic bone infarctions was diagnosed (both femoral condyle and proximal tibias). Patient 3 showed an asymptomatic area of bone edema in distal left radial bone.

Summary/Conclusion:

Although the sample from our study is very small, it seems that WB‐MRI could be useful to evaluate vascular events, like bone infarctions, even subclinical ones. Our findings are consistent with the only article published to date (Alaskar et al. Sci Rep. 2018; 8: 13458). Further studies are needed to test the effectiveness of WB‐MRI in the detection of vascular events and their relationship as a thrombotic event in PNH.

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PB1878 β‐CATENIN IS AN EFFECTOR OF THE CROSS‐TALK BETWEEN CLL B‐CELLS AND THE MICROENVIRONMENT
Authors: Ouriemmi S. , Varin‐Blank N. , Ledoux D. , Gardano L.
Published: June 2019

Background:

CLL is a lymphoproliferative disorder characterized by the accumulation of CD5+ B cells in the blood and lymphoid organs (bone marrow, lymph nodes and spleen). This accumulation is mainly due to an increased survival and proliferation of tumor B cells within the lymphoid organs through interaction with the microenvironment as isolated B‐CLL cells rapidly undergo apoptosis in vitro. In the quest for the molecular basis of the communication between B‐CLL cells and the microenvironment, we focused our attention on β‐catenin that participates to the stabilization of cell‐cell contacts and signal transduction. Cytosolic β‐catenin level is maintained low following its phosphorylation that triggers the degradation by the proteasome. Several molecules, such as Wnt ligands inhibit β‐catenin phosphorylation and induce its stabilization.

Aims:

The aim of our study is to evalute the role of β‐catenin in the cross talk between CLL B cells and the microenvironnement.

Methods:

Co‐cultures of primary B‐CLL cells and human bone marrow stromal cells line (HS‐5).

Results:

Using a model of co‐culture of primary B‐CLL cells and human marrow stromal cells we observed that the co‐culture rapidly stabilizes β‐catenin in B‐CLL cells. Since in B‐CLL cells the pathway linked to antigen stimulation is essential for survival, we explored whether β‐catenin stabilization involve BCR pathway effectors. Interestingly, we observed that the inhibition of the kinase BTK hampers β‐catenin stabilization in presence of stromal cells. Concomitant with the participation of BTK, a phosphatase activity is involved in β‐catenin stabilization. We are currently addressing whether and how the stabilization of β‐catenin regulates cell survival and the interactions between B‐CLL and stromal cells.

Summary/Conclusion:

Our results will convey new elements to describe the cross‐talk between tumor cells and the microenvironment to define new targets that interfere with this dialogue as alternative therapeutic strategies.
PB1916 MIRNAS AND ANGIOGENIC FACTORS IN PLASMA BEFORE AND AFTER TKI TREATMENT IN CML PATIENTS
Authors: Litwińska Z. , Łuczkowska K. , Sobuś A. , Rogińska D. , Pius‐Sadowska E. , Paczkowska E. , Gniot M. , Lewandowski K. , Helbig G. , Machaliński B.
Published: June 2019

Background:

The differences of an angiogenic potential between clinical phases of chronic myeloid leukemia (CML), point at the significance of neovascularisation in CML pathogenesis. Tyrosine kinase inhibitors (TKI), possessing antiangiogenic properties and microRNAs (miRNAs), implicated in governing angiogenesis, both seem vital in this process.

Aims:

In this study, we aimed to investigate how TKI treatment affects angiogenesis‐related miRNAs expression and angiogenic factors concentration in plasma of CML patients.

Methods:

Peripheral blood plasma samples were obtained from CML patients at the diagnosis (n = 23) and during TKI treatment (n = 12). Quantitative assessment of the expression of miRNA‐126‐3p, miRNA‐150‐5p and miRNA‐21‐3p was performed with qRT‐PCR. Concentrations of selected angiogenic factors in plasma (Angiogenin, bFGF, Endostatin,aFGF, PDGF‐AA, PIGF, Thrombospondin‐2, VEGF‐D, Angiopoietin‐1, VEGF) were assessed using multiplex fluorescent bead‐based immunoassays (Luminex Corporation).

Results:

MiRNA‐150‐5p and miRNA‐21‐3p expression was evidently higher in the treatment group (p = 0,001 and p = 0,03, respectively). PDGF‐AA concentration in newly diagnosed patients with CML was higher than in already treated patients (942,84 pg/ml vs 512,5 pg/ml, p = 0,02), similarly to VEGF (262,82 pg/ml vs 27 pg/ml, p = 0,03).

Summary/Conclusion:

TKI treatment affects miRNAs expression and angiogenic factors concentration in plasma of CML patients. MiRNAs could serve as biomarkers in monitoring CML progression and drug response, however, their exact role in CML‐related angiogenesis remains to be further elucidated.
PB1937 CHROMOSOMAL ABERRATIONS IN CHRONIC MYELOID LEUKEMIA AND THEIR IMPACT ON RESPONSE TO CONVENTIONAL TYROSINE KINASE INHIBITORS AND RISK OF BLASTIC TRANSFORMATION.
Authors: Maqsood S. , Ali F. , Siddiqui N. , Hameed A.
Published: June 2019

Background:

Chronic Myeloid Leukemia(CML) is a common hematological malignancy with tyrosine kinase inhibitors(TKI) forming the main stay of treatment.

Aims:

The purpose of this project was to study the clinical presentation of patients with CML harboring additional chromosomal abnormalities at diagnosis and disease outcomes.

Methods:

This is a retrospective chart review of all patients who were diagnosed with CML in chronic phase (CP) with additional chromosomal abnormalities (ACAs) over a period of 5 years from 2010 to 2015 at our institution.

Results:

Response to initial TKI

A total of 283 patients were diagnosed with CML from January 2010 to January 2015. Thirty one patients were found to have ACAs at the time of diagnosis in addition to BCR‐ABL fusion gene.

23 patients (74.2%) were males whereas 8(25.8%) were females. 13(41.9%) were in the age group of 31 to 50 years. 30 patients were started on Imatinib and one on Nilotinib. 16 patients (51.6%) achieved complete hematological response within 3 months. However a complete molecular and cytogenetic response was never achieved in 17 (54.8%) and 18 (58.1%) patients respectively.

Cytogenetics Analysis and ACAs

Conventional cytogenetic analysis revealed that 11 (35.5%) of patients had variant Philadelphia chromosome followed by 7 patients (22.6%) with trisomy 8. 5 patients (16.1%) had multiple chromosomal abnormalities including trisomy 8, deletion 1 and isochrome 17q.

Risk of blastic transformation

Eight patients (25.8%) transformed to acute myeloid leukemia(AML) whereas 3 (9.7%) patients had a transformation to acute lymphoblastic leukemia(ALL).

Therapy and response in transformed patients

Out of the 11 patients who transformed to AML and ALL, 6 patients underwent induction chemotherapy while 5 were not considered fit for it on account of poor performance score and lack of resources. Out of these 6 patients, none responded to induction chemo.

Summary/Conclusion:

In summary, this study aimed to look at the clinical presentation of patients with CML harboring additional chromosomal abnormalities at diagnosis, cytogenetic analysis, risk of blastic transformation and response to treatment in transformed patients. Despite an early hematological response, more than half of the patients failed to achieve complete molecular and cytogenetic response which clearly shows suboptimal response to the tyrosine kinase inhibitors in this particular set of CML patients. There was transformation to acute leukemia in 35.5% of patients. We were able to give induction chemotherapy to only 6 out of 11 patients and none of them responded to it. This study showed that presence of ACA at the time of diagnosis is a high risk feature for patients with CML and confers poor prognosis when treated with conventional TKI. Further studies are required in our population regarding alternative therapy for such patient population.
PB1945 EXPERIENCE OF THE ANDALUSIAN CHRONIC MYELOID LEUKEMIA GROUP (GALMC) IN THE DISCONTINUATION OF THE TYROSINE KINASE INHIBITOR TREATMENT OUTSIDE OF CLINICAL TRIALS
Authors: Alarcón‐Payer C. , Puerta Puerta J.M. , Jiménez Morales A. , Ramírez Sánchez M.J. , Montero Cuadrado M.I. , Mata Vázquez M.I. , Ferrer Chaves C. , Anguita Arance M. , Vera Goñi J.A. , García Pérez M.J. , Mellado Gázquez Á. , Moatassim de la Torre Y. , Hermosín Ramos L. , Jurado Chacón M. , López Garrido P.
Published: June 2019

Background:

Currently one of the most burning issues regarding the specific treatment of Chronic Myeloid Leukemia (CML) with Interleukin‐2‐inducible T‐cell kinases (ITKs) is whether in a percentage of patients who meet specific requirements treatment interruption could be attempted and maintain molecular relapse‐free survival without treatment restarting with the consequent reduction of side effects related to medication and the progressive increase in the quality of life of patients.

Aims:

To analyse molecular relapse‐free survival after suspension of Imatinib, Nilotinib or Dasatinib, which achieved and maintained a Molecular Response ≥ 4.5 log for at least 36 months.

Methods:

Multicenter prospective observational post‐authorization follow‐up study of patients with Chronic Phase Ph+ CML (CP‐CML). Inclusion criteria: minimum ITK treatment time of 5 years, no resistance to a previous ITK, no accelerated phase diagnosis or blast crisis and those who have achieved and maintained the Molecular Response ≥ 4.5 log for at least 36 months prior to treatment interruption. These patients were candidates for discontinuation of ITKs. Molecular monitoring of bcr‐abl oncogene levels was performed using the Real‐Time Reverse Polymerase Chain (RT‐PCR) technique with the GeneXpert automated system with a sensitivity of 5 log.

Results:

71 patients with CP‐CML were discontinued. 51 discontinued Imatinib treatment, 7 discontinued dasatinib treatment and 12 discontinued Nilotinib treatment. The preliminary rates of Molecular Relapse Free Survival (MRFS) and Treatment Free Remission (TFR) are consistent with those obtained in the different clinical trials, and no progression to advanced stages of the disease has been reported. With a median follow‐up of 9 months, 78% remain without specific treatment with ITK for not having lost the major molecular response, (BCR ABL ≤ 0.1%) cut‐off point established in the study as a criterion for reintroduction of ITK treatment. Relapse occurred before 6 months of discontinued treatment with a median of 3 months.

Summary/Conclusion:

Discontinuation of treatment with ITKs translates into clinical benefit for patients with CP‐CML, as it would reduce treatment‐related side effects and improve quality of life.
PB1955 REAL LIFE DATA OF NILOTINIB IN PATIENTS WITH CHRONIC MYELOID LEUKEMIA RESISTANT OR INTOLERANT TO IMATINIB
Authors: Tuğlular A.T. , Elibol T. , Memiş T. , Aldağ B. , Dedeoğlu Ö. , Ercan T. , İpek Y. , Arıkan F. , Yılmaz A.F. , Kaygusuz Atagündüz I. , Toptaş T.
Published: June 2019

Background:

Nilotinib is an effective treatment option for patient's refractory or intolerant to imatinib and can be given as 2nd or 3rd line treatment in Turkey.

Aims:

In this retrospective study, we aim to demonstrate the frequency of side effects in patients on Nilotinib.

Methods:

We analyzed 253 patients with chronic myeloid leukemia (CML) followed by Marmara University Hematology Department. 53 of these patients (%20.9) were on Nilotinib in a period of their treatment. Clinical characteristics of the patients are given in table 1.

Results:

Median duration of patients on imatinib before switching to 2ndline TKI were 19 months (1‐96). Reasons for changing therapy were primary imatinib resistance in 13 patients (%24.5), loss of response in 31 patients (%58.4), drug intolerance in 8 patients (%15.1). In one patient cause of treatment change could not be found.

Nilotinib was used as 2nd line TKI in 37 of patients (%69.8) and was used after Dasatinib as 3rd line TKI in 16 of patients (%30.2). Median dasatinib treatment duration before switching to nilotinib was 14 months. Reasons for switching to nilotinib therapy were primary resistance in 3 patients (%18.7), loss of response in 4 patients (%25) and drug intolerance in 8 patients (%50).

Nilotinib dosage were 800 mg, median duration of treatment on Nilotinib was 28 months (1‐120). 31 patients (%58.5) are still on Nilotinib. Reasons for discontinuation were primary Nilotinib resistance in 3 patients (%5.6), loss of response in 6 patients (%11.3) and drug intolerance in 8 patients (%15.1). Five patients were lost to follow up.

Adverse events were seen on 21 patients (%39.6) and 9 of these (%17) were serious adverse events (SAE). SAE were ischemic cerebrovascular disease in 1 patient, myocardial infarct (MI) in 3 patients, acute pancreatitis in 2 patients, treatment‐resistant nausea‐vomiting in 1 patient, treatment‐resistant rash in 1 patient and grade IV thrombocytopenia in 1 patient. Treatment duration of Nilotinib in patients with MI were 24, 45 and 50 months. Cardiovascular risk factors were not observed in 2 of 3 patients who had MI; other patient had diabetes and hypertension. Treatment duration of Nilotinib in patients with pancreatitis were 1 and 25 months.

Summary/Conclusion:

In conclusion, Nilotinib is a highly effective treatment for patients who are refractory or intolerant to imatinib or dasatinib. Patients should be followed carefully in terms of side effects such as MI, arterial occlusive diseases and pancreatitis.

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PB1958 SUDDEN ONSET HEARING AND VISUAL LOSS: AN UNUSUAL PRESENTATION OF CHRONIC PHASE CHRONIC MYELOID LEUKEMIA
Authors: S.  , Tandon S. , Gupta R. , Nityanand S.
Published: June 2019

Background:

Hearing loss and blindness are seldom encountered as primary manifestations in patients with chronic myeloid leukemia. Chronic myeloid leukemia (CML) commonly presents with weakness, dysphagia, abdominal distension and pain and rarely constitutional symptoms. Chronic myeloid leukemia rarely presents with auditory or visual manifestations. Hyperleukocytosis at presentation can lead to obstruction of the small vessels of mainly brain, lungs and kidneys leading to organ dysfunctions. Headache, convulsions, stroke, papilledema, hearing loss, tinnitus and vertigo constitute the rare neurological spectrum of CML.

Aims:

We present a case series of four patients who presented with bilateral sudden onset of hearing and visual loss. This report highlights the unusual presentation of chronic phase CML with visual and sensorineural hearing loss.

Methods:

A detailed evauation of hisory, clinical examination, ENT & Eye examination was done in each patients. Related radiological evaluation was done as needed.

Results:

Chronic myeloid leukemia rarely presents with visual or hearing loss and till date, only 29 cases of CML with deafness have been reported. Neurological involvement including deafness, blindness and tinnitus was reported as 15.5% in a series of 33 adults with CML. Otological findings, for instance, sudden hearing loss, vertigo, tinnitus, facial weakness, and infection, were found in 16–40% of patients. However, deafness as an initial sign of this disease is very rare. Bilateral sudden sensorineural hearing loss, vertigo, and nausea were the presenting manifestations of CML in our patients. CML associated deafness presents itself as sensorineural, unilateral, bilateral or starting unilaterally and developing into bilateral. The pathogenesis of this clinical symptom in leukemia is very complex, and may include multiple mechanisms such as leukemic infiltration, hyperviscosity syndrome, inner ear hemorrhage, and infection. A relationship between leukemic infiltration of the cochlea and impairment of hearing in CML has also been mentioned in literature. Cochlear and retinal blastic infiltration may also cause sensorioneural deficit other than leukostasis in CML. Inner ear hemorrhage has been shown as a cause of sudden hearing loss in leukemia by some authors. Hyperleukocytosis is considered to be the foremost pathogenesis of CML with hearing loss, as suggested by recovery of hearing upon leukapheresis in some cases.

Summary/Conclusion:

CML should be considered as one of the rare diagnostic possibilities in patients presenting with sudden onset of hearing and visual impairment and managed on an emergent basis as delay can result in permanent impairment.

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PB1965 CLINICAL UTILITY OF RETICULOCYTE HEMOGLOBIN EQUIVALENT TO DIFFERENTIATE BETWEEN FUNCTIONAL IRON DEFICIENCY ANEMIA AND TRUE ANEMIA AND DIFFERENT FROM ANEMIA OF OTHER CAUSES OF CHRONIC DISEASE.
Authors: Lourenco E.M. , Thomas N. , ANTIA D.V.
Published: June 2019

Background:

Iron Restricted Erythropoiesis can be:

1.Absolute iron deficiency

2. Iron sequestration [impaired iron trafficking]

3. Functional iron deficiency [FID]

4. Heriditary conditions with impaired iron transport & utilization.

Anaemia of chronic disease [ACD] is defined as hypoproliferative anaemia of no apparent cause.

Ret He is hemoglobin content equivalent of reticulocytes.Monitors iron supply during erythropoiesis over last 2‐3 days, increases within 2‐4 days of iron therapy

Aims:

To compare Ret He and % Hypo values with standard biochemical markers of iron metabolism: serum iron, TIBC, Transferrin saturation, serum ferritin, sTfR [Soluble Transferrin Receptor] levels and to assess in diagnosing iron deficiency.

Methods:

[n = 120] analysed [15 M: 10 F ratio,age 10 – 87 yrs]

CBC samples [K2 EDTA] analysed on Sysmex XN1000 series.Ret He and Hypo He % identified in the reticulocyte channel by Fluorescence flowcytometry using polymethine dye

Patients with Haemoglobin < 10 g/dl tested

[1]:Normal patients [n = 25] 20.8 %. [2]: IDA Patients [n = 45] 37.5 %. [3]: CKD Patients on haemodialysis treated with variety of erythropoietin doses [n = 12] 10 %. [4]: CKD Patients [n = 7] 5.8 %. [5]: ACD Patients [n = 31] 25.8 %.

Ret‐He: Sensitivity: 97.87 %,Specificity: 96.15 %,PPV: 98.92 %,NPV: 92.59 %

Results:

20 % Normal patients Ret He 33 pg

In 5% of ACD,IDA co‐existented so differentiate ACD and ACD/IDA as iron supplementation is beneficial for ACD/IDA patients but deleterious for ACD patients.

37 % IDA Patients Ret He was < 23.6 pg.

3.3 %patients of thalassemia with IDA, Ret‐He: 19.5pg.

STfR elevated in IDA cases, but was normal in ACD &FID cases

Hypo He % in FID [> 5%],IDA [>10%] ACD [<5 %]. Hypo He % measure is time average marker of iron restricted erythropoiesis [20‐120 days].

10% CKD patients on erythropoietin doses Ret‐He < 25.5 pg presents FID

Normal Range for Ret He: 31‐35 pg.

Summary/Conclusion:

Serum Iron, TIBC, % T Sat. Screens anemia but Ret He detects & gives expended information at cellular levels so assess true status of iron and predictor of marrow iron stores

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Detects IDA, FID, ACD which helps differential diagnosis

Ret He < 23.6 pg. suggest classical iron deficiency & also predicts FID in those receiving ESA [erythropoietin stimulating agent] therapy. Indicates a non responder to rHuEPO/ ESA or FID
PB1969 CYP2D6 ALLELIC CHARACTERIZATION ON SPANISH TYPE 1 GAUCHER DISEASE PATIENTS
Authors: López de Frutos L. , Alfonso P. , Lahoz C. , Irún P. , Giraldo P.
Published: June 2019

Background:

Cytochrome p450 is the main drug metabolic pathway mostly by CYPIIIA4 and CYPIID6 enzymes. The second one is the responsible for the clearance from 20% of most common drugs as paracetamol or codeine and presented four different metabolizer phenotype: normal metabolizer (NM), intermediate metabolizer (IM), poor metabolizer (PM) or ultra‐rapid metabolizer (UM). CYP2D6 (MIM∗608902) is a highly polymorphic gene that encodes CYPIID6. The different metabolizer capabilities are caused by different alleles on CYP2D6 due to entire gene deletions or duplications or 19 SNPs. This is the pathway to metabolize one of the Gaucher disease (GD) treatments, which dose administration is regulated according to the metabolizer phenotype being this one of the administration limitations

Aims:

With this background we consider interesting stablish the metabolizer and allelic frequency from CYP2D6 on our GD population and compare it with the general Spanish population and a Gaucher disease patients cohort.

Methods:

We select 109 type 1 GD patients genetically confirmed and we used the xTAG®CYP2D6 kit to identify the CYP2D6 gene alleles. This group was compared with a control group obtained from the completed Spanish reports on the pharmagkb database and with a worldwide type 1 GD patients enrolled on the ENCORE trial. Statistical significance was considered if p‐value<0.05

Results:

As a result, 87 patients were classified as normal, 14 as intermediate, 6 as poor and 2 as ultra‐rapid metabolizers. The allelic frequencies were 5.5% for duplication and 4.5% for deletion. The most common allele was wild type and the second one was the null allele ∗4. Alleles ∗6, ∗9 and ∗35 presented a higher frequency than expected. There was no relationship between the patients’ gender or GBA1 genotype and the allelic or phenotypic frequencies on CYPIID6 enzyme and CYP2D6 gene. This results were different than expected for Spanish population but agrees with the ENCORE Gaucher cohort.

Summary/Conclusion:

To sum up, our Spanish GD series shows an unexpected distribution of alleles that encode for an enzyme with a reduced or absent activity than the results previously reported in the Spanish population. This is important due to the pharmacological interactions and the impact of unexpected secondary effect that can be higher on this population.
PB1971 STEPWISE APPROACH TO UNDIAGNOSED ANEMIA IN CHILDREN: A MODEL FOR LIMITED RESOURCES SETTINGS
Authors: Elalfy M. , Elhabashy S. , Ragab I. , Mowafy N. , Sallam M. , Russo R. , Iolascon A. , Hussein N.
Published: June 2019

Background:

Undiagnosed inherited anemia is a unique clinical entity in tertiary hematology centers. Reaching confirmed diagnosis is challenging and requires series of complex expensive investigations.The high prevalence of iron deficiency and thalassemia carriers makes the diagnosis of other classes of anemia more challenging.

Aims:

we aimed at plotting a stepwise diagnostic approach in children with undiagnosed anemia which can be applied in restricted resource settings.

Methods:

A cross‐sectional study involved 45 still undiagnosed anemia patients after routine panel of investigations. They were classified based on mean corpuscular volume (MCV) into 3 groups; microcytic (n = 19),normocytic (n = 14) and macrocytic group(n = 12). An algorithm was plotted for each category including 4 levels of investigations. The fourth level analysis included genetic based analysis in appropriate setting.

Results:

After applying a systematic approach; 24 (54%) were probably diagnosed, 8 (18%) confirmed diagnosis,3 (6%) combined diagnosis and 10 (21%) patients remain undiagnosed. By primary, second, third levels; 9 patients were (5 microcytic,3 normocytic,1 macrocytic),8 (4 microcytic,2 normocytic,2 macrocytic) and 18 patients (5 microcytic, 8 normocytic,5 macrocytic) were diagnosed respectively; while 10 patients necessitated a fourth line level (8 microcytic and 2 normocytic).The diagnoses attained in microcytic group were hemoglobinopathies (42%),iron refractory iron deficiency anemia (IRIDA) (15%), membrane defect (10%), sideroblastic anemia (10%),hypotransferrenemia (5%), 15 % combined diagnosis (iron deficiency anemia and beta thalassemia minor, one sickle cell disease with pyropoikilocyosis and one alpha thalassemia and hereditary spherocytosiswhile15% remained undiagnosed. In normocytic group, the diagnosis washerediatary spherocytosis (20%), pyruvate kinase deficiency(15%), CDA type II (28%), beta thalassemia major (7%),Diamond Blackfan anemia (7%), vitamin B12 deficiency (15%) and 30% with no confirmed diagnosis,. In the macrocytic group, vitamin B12 deficiency (25%), PK deficiency(8%), sideroblastic anemia(8%) CDA II (16%) and 40% undiagnosed;by applying the four level of investigation, diagnosis was changed in 2,7 and 7 in microcytic, normocytic and macrocytic respectively.

Summary/Conclusion:

Setting a stepwise approach with different levels of may help to reach diagnosis of difficult anemia without performing unnecessary investigation showed that microcytic anemia was more frequent.High frequency of B12 deficiency presented either as normocytic or macrocytic was reported in this study. 40% remained with indefinite diagnosis after series of investigations
PB1979 ONLINE CME AS A TOOL TO INCREASE CLINICIANS’ KNOWLEDGE OF CLINICAL TRIAL DATA FOR GENE THERAPY IN HEMOPHILIA
Authors: Hurst S. , Warren C. , Kadkhoda H.
Published: June 2019

Background:

Gene therapy has the potential to fundamentally alter care for patients living with hemophilia. To educate and prepare clinicians for this potential paradigm shift, the National Hemophilia Foundation (NHF), European Haemophilia Consortium (EHC), the World Federation of Hemophilia (WFH), and Medscape Education established a multinational collaboration to develop an online continuing medical education (CME) curriculum.

Aims:

The current study assessed the ability of online CME to improve clinicians’ knowledge regarding the latest data from ongoing trials for gene therapy in hemophilia.

Methods:

A 15‐minute, CME‐certified, Expert Video Commentary activity was developed and launched online on 09/25/2018. Educational effectiveness was assessed with a repeated‐pairs pre‐/post‐assessment study design, with each individual serving 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, 2,747 clinicians, including 2,229 physicians, have participated in this educational activity. This analysis comprises data from the subset of hematologists/oncologists (n = 84; hem/oncs) and pediatric hematologists (n = 223) who answered all pre‐/post‐assessment questions during initial analysis period of 09/25/18 thru 11/09/18; data collection is ongoing.

Both hem/oncs and pediatric hematologists exhibited significant improvements overall and in specific areas of assessment (Figure). A notable proportion of providers – 17% of hem/oncs and 35% of pediatric hematologists – expressed increased confidence with regard to their understanding of the latest safety and efficacy data for gene therapy. In addition to the positive impact of education, these findings also uncovered educational gaps, such as the need for additional education regarding vector‐related molecular biology, design, and dosing considerations. These topics may be the focus of future CME programs.

Summary/Conclusion:

Hematologists/oncologists and pediatric hematologists who participated in this online, Expert Video Commentary activity demonostrated significantly improved knowledge of efficacy and safety data from clinical trials in hemophilia.

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PB1982 AN IN VITRO STUDY OF THE INTERACTIONS BETWEEN THE CELL BASED CANCER VACCINE DCP‐001 AND ANTIGEN PRESENTING CELLS
Authors: Singh S.K. , van Lierop M.‐J. , Kaspers J. , Bos R. , Kamermans A. , de Vries H.E. , Manting E.H.
Published: June 2019

Background:

DCP‐001 is a whole cell‐based vaccine derived from the DCOne® human myelomonocytic leukemic cell line. DCOne cells endogenously express known and unknown tumour‐associated antigens. In the DCP‐001 manufacturing process, DCOne cells are differentiated and matured into cells with a mature dendritic cell phenotype. A phase I clinical trial demonstrated that the vaccine is safe and induces local and systemic cellular and humoral immune responses. DCP‐001 is currently studied in an international Phase II trial in AML patients ineligible for HSCT.

Aims:

To study the role of the interaction of whole cell‐based vaccine DCP‐001 with host immune cells.

Methods:

DCP‐001 and antigen presenting cell interaction studies were performed using flow cytometry and confocal microscopy. Cytokine/chemokine analyses were performed using luminex technology.

Results:

The strong immunogenicity of DCP‐001 is demonstrated by the broad range of chemokines and pro‐inflammatory cytokines released upon co‐culture of DCP‐001 with human peripheral blood mononuclear cells. Using different methods, we further demonstrate that antigen presenting cells efficiently process DCP‐001 through phagocytosis.

Summary/Conclusion:

These in vitro data suggest that in vivo, upon intradermal injection, DCP‐001 induces a strong inflammatory response, and is ingested by both resident as well as attracted host's APC, which subsequently prime tumour‐reactive T cells.
PB1992 HEMATOPOIETIC LIKE CELLS DERIVED FROM CANCER STEM CELLS GENERATED FROM MOUSE INDUCED PLURIPOTENT STEM CELLS: NOVEL CONCEPT FOR CANCER ASSOCIATED HEMATOPOIESIS
Authors: Hassan G. , Afify S.M. , Kumon K. , Zahra M. , Okada N. , Seno A. , Seno M.
Published: June 2019

Background:

Cancer stem cells (CSCs) represent the subpopulation of cancer cells with plasticity to differentiate into other cell phenotypes. Previously, we reported to generate cancer stem cells from mouse induced pluripotent stem cells with the potential to develop endothelial cells and cancer associated fibroblasts of angiogenesis. In the other hand, recent reports showed that erythrocytes could be derived from the tumor. However, the ability of CSCs to exhibit different hematopoietic cells is still unclear.

Aims:

To investigate the hematopoiesis phenomena from CSCs in vitro.

Methods:

Viability of non‐adherent cells (NACs) arising from cancer stem cells (expressing GFP under Nanog promoter) was analyzed by flow cytometry using Annexin V and PI. The morphology and expression of CD34 and LIN markers were also investigated using Giemsa staining, flow cytometry, and immunofluorescence staining, respectively. Molecular phenotype of NACs was examined by RT‐PCR. Clonogenic assay was conducted by culturing NACs on mouse embryonic fibroblast (MEF).

Results:

The round nucleated cells with heterogeneous diameter were observed on the surface of cancer stem cells adhered on the bottom of dish. Approximately 80% of NACs were found viable according to Annexin V and PI staining while 60% were positive for Lin markers and 0.35% were positive for CD34.

NACs were found to express hematopoietic marker genes for CD34, CD38, CD10, c‐Kit and EPO‐R by RT‐PCR as well as to form colonies on MEF.

Summary/Conclusion:

CSCs were demonstrated to have potential to provide progenies with hematopoietic marker and morphology as cancer associated hematopoietic cells, which could give a new insight of tumor microenvironment according to the plasticity of cancer stem cells.