bluuebunny/crossref_metadata_2025_split huggingface dataset:
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.image
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.image
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 deficiency2. 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 therapyAims: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 dyePatients 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 pgIn 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 casesHypo 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 FIDNormal 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
imageDetects 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 limitationsAims: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<0.05Results: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.image
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.