bluuebunny/crossref_metadata_2025_split huggingface dataset:
PB1735 POSTDIAGNOSIS SMOKING WITH RISK OF ALL‐CAUSE AND CANCER MORTALITY AMONG LEUKEMIA SURVIVORS: A PROSPECTIVE COHORT STUDY
Authors: Tao H. 
Published: June 2019

Background:Smoking is associated with higher leukemia risk, but smoking and risk of all‐cause and cancer mortality among leukemia survivors is unclear.Aims:To evaluate more thoroughly the risk of all‐cause and cancer mortality between cigarette smoking and leukemiaMethods:We identified 316 subjects who were diagnosed with leukemia from National Health Interview Survey participants≥18 years of age from 13 cross‐sectional waves conducted during 1997 to 2009 (linked to mortality data in 2015) at baseline. Cox proportional hazards regression models were used to calculate adjusted hazard ratios (HRs) with 95% confidence intervals (CIs) for the risk of all‐cause and cancer mortality caused by smoking exposure.Results:After a median follow‐up of 13 years, 141 (50%) were alive and 141 (50%) died due to all‐cause mortality during the follow‐up. Of all the patients who died, 70 (50%) died due to cancer and 20 (14%) died due to cardiovascular disease (CVD). Compared to never smokers, former smoking could increase the risk of cancer mortality (HR, 1.95; 95%CI, 1.04‐3.68), especially for those who quit smoking recently (HR, 2.59; 95%CI, 1.17‐5.74). For cancer mortality, dose relationship was obvious among former smokers who had quit more recently than for those who had quit earlier with a “U” shaped curve (Ptrend < 0.05). Current smokers who smoke less than 10 cigarettes per day had higher risk of cancer mortality (HR, 3.72; 95%CI, 1.01‐13.73) than never smoking when patients with a history of CVD were excluded.Summary/Conclusion:This study adds to the existing evidence that cigarette smoking is associated with higher cancer mortality among leukemia patients, especially for former smokers.image
PB1736 IMPACT OF BCR FUSION TRANSCRIPTS ON OUTCOMES IN ACUTE PROMYELOCYTIC LEUKEMIA (APL)
Authors: Pydi V.R. , Chowdary B.S. , Yedla R.P. , Gundeti S. 
Published: June 2019

Background:Acute promyelocytic leukemia (APL) results from fusion of PML RARα gene and accounts for 10% of AML. The breakpoints on chromosome 17 are consistently located in the second intron of the RARα gene, but on chromosome 15, there are different breakpoint cluster regions, namely bcr1, bcr2, and bcr3 located in intron 6, exon 6, and intron 3, respectively. About 70% of patients with APL have bcr‐1 or long (L)‐type transcript, 20% of patients with APL have bcr‐3 or short (S)‐type transcript, and 10% of patients have bcr‐2 or variant (V)‐type transcriptAims:The primary objective of this analysis was to study patient characteristics and outcomes in relation to bcr fusion transcripts of APLMethods:Data of all patients diagnosed as APL by PCR for PML RARα with known bcr transcripts were retrospectively analysed. Deaths within 72 hours of admission were excluded from the study. Statistical analysis was done using SPSS software, version 25. Overall survival was plotted using the Kaplan‐Meier methodResults:A total of 54 patients were analysed. bcr 1, bcr 3, bcr 2 and bcr 2’3 transcripts were seen in 29(53.7%), 20(37%), 3(5.6%) and 2(3.7%) respectively. Ten out of 11 paediatric patients (91%) had bcr1 transcript at presentation. The baseline characteristics and chemotherapy regimens used are tabulated in Table 1. Differentiation syndrome during induction chemotherapy was seen in 6 (21%) and 3 (15%) patients in bcr1 and bcr 3 transcripts respectively. Five patients with bcr3 transcript, 2 patients with bcr1 transcript and one patient each in bcr2 and bcr2’3 transcripts succumbed during induction therapy. Sepsis (45%), followed by DIC (45%) were the most common causes of mortality. At a median follow up of 19 months, the overall survival rate was 93.1% and 74.3 % in bcr1 and bcr3 transcript groups respectively (p = 0.09).Summary/Conclusion:Most of the paediatric patients had bcr1 transcript at presentation. High risk at presentation was significantly higher in bcr3 group. Sepsis and DIC were the most common causes of induction mortality. Patients with bcr3 transcript had nonsignificant inferior survival compared to bcr1image
PB1759 DNMT3A MUTATION IS NOT RELATED WITH UNFAVORABLE CLINICAL OUTCOME IN ACUTE MYELOID LEUKEMIA PATIENTS
Authors: Lee Y.K. , Lee J. , Jeon K. , Kim M. , Han B. , Kim H.J. 
Published: June 2019

Background:Mutation in DNMT3A (DNA methyltransferase 3A) has been identified as a key factor in the development of hematological malignancy. While some previous reports have suggested that DNMT3A mutation is related with negative outcome in acute myeloid leukemia (AML) patients, the clinical implication and prognostic significance of DNMT3A mutation in AML is still debated.Aims:We intended to investigate the incidence of DNMT3A gene mutation and its association with clinical and laboratory findings and prognosis in Korean AML patients.Methods:From 2012 to 2018, we enrolled forty‐nine patients diagnosed with AML without recurrent genetic abnormalities. We performed Sanger sequencing to analyze DNMT3A mutation using residual bone marrow samples. We also collected other laboratory data and clinical information via electronic medical records.Results:We found DNMT3A mutations in 6 out of 49 AML patients (12.2%). Five patients had the R882H mutation, and one patient the R882C mutation. There was no significant difference in age, complete blood cell count (CBC) parameters, or bone marrow (BM) blast % between the groups with and without DNMT3A mutations. The portion of patients older than 60 years was smaller in DNMT3A mutation positive group (33.3% vs. 60.5%, p = 0.381). DNMT3A mutation group showed higher rate of complete remission (CR) (50% vs. 27.9%, p = 0.353), shorter period to CR (1.1 (CI 1.1 – 1.2) months vs. 1.2 (CI 1.0 – 2.8) months, p = 0.613), and lower relapse rate after CR (0% vs. 41.7%, p = 0.505) than DNMT3A mutation negative group although the difference was not statistically significant. In the survival analysis, the median overall survivals (OS) were 29.0 (CI 5.5 – 52.4) months for DNMT3A mutation positive group and 10.8 (CI 0.5 – 21.0) months for DNMT3A mutation negative group. The median progression free survivals (PFS) were 29.0 months (CI 5.5 – 52.5 months) for DNMT3A mutation positive group and 8.0 months (CI 0.0 – 16.3 months) for DNMT3A mutation negative group. However, the effect of DNMT3A mutation on OS and PFS was not statistically significant (p = 0.814 and p = 0.528, respectively). In a multivariate analysis, the only independent predictive factors for survival were age (HR: 1.027, p = 0.001) and BM blast % (HR: 1.017, p = 0.016). DNMT3A mutation, sex, and CBC parameters were not independent predictors of survival.Figure 1. Kaplan‐Meier overall survival analysis (A) and progression‐free survival analysis (B) comparing between the groups with and without DNMT3A mutation.Summary/Conclusion:The incidence of DNMT3A mutation was 12.2% in Korean AML patients. DNMT3A mutation tended to be related with favorable outcome although statistically insignificant. This statistical insignificance might be due to the small sample size. Considering all, our results at least provide support for the view that DNMT3A mutations is not an unfavorable prognostic factor in AML patients.image
PB1771 EFFECTS OF AJWA ON DISEASE COMPLICATIONS AND CARDIAC AMONG HEMATOLOGICAL MALIGNANCY AND AJWA NANOFORMULATIONS ON THE ANTI‐CANCER AND SAFETY
Authors: Al Jaouni S. , Hussein A. , Ezzat D. , Almuhayawi M. , Raddadi R. , Mousa S. 
Published: June 2019

Background:Phoenix dactylifera, (Ajwa) has been known for a long time for its nutritive and medicinal properties.Aims:To evaluate the benefit of Ajwa in minimizing disease complications and cardiac on Pediatric Hematological malignancy at King Abdulaziz University Hospital, Jeddah, Saudi Arabia and to preclinically evaluate Nanoformulated Ajwa Bioactive compounds (N‐Ajwa) on Anti‐cancer efficacy and prevention of cardiac toxicity‐mediated by Doxorubicin (DOX).Methods:Our investigation include clinical and preclinical studies. The clinical study is a controlled trial of pediatric cancer patients between 2008 and 2018. A total of 200 patients were screened. Out of the 200 patients, 56 patients were included, 10 patients were AML (17.8%). Out of those 56, 26 (46.43%) agreed to take Ajwa and 30 served as control (53.57%). Both groups were assessed based on the following parameters: infection rates, frequency of hospital admissions for fever neutropenia, safety and mortality rate. The preclinical study examined the impact of N‐Ajwa on the anti‐cancer efficacy and cardiac safety of DOX in human breast cancer in female nude mice model.Results:Out of the 56 patients included, twenty six patients opted to be on Ajwa and the rest served as control. The supplementation of Ajwa significantly reduced hospital admissions and infections (P = 0.009 and P < 0.001 respectively). Ajwa group had a better survival rate in comparison to those in the non‐Ajwa group (stratified log‐rank P = 0.005), where the main cause of death of patients on the non‐Ajwa group was disease progression associated with infections (77%), cardiac problems were documented in 3 AML patients(30%). Those who were compliant on Ajwa showed recovery of cardiac problems. Ajwa showed some sort of cardiac protection in cardiac patients. N‐Ajwa bioactive ingredients protected against cardiac toxicity without any impact on anti‐cancer effects of DOX.Summary/Conclusion:This controlled study showed the regular intake of Ajwa is safe and significantly decreases disease complications including cardiac and infection and improved survival. Additionally, Ajwa have an effective role in cardiac protection against Doxorubicin.
PB1845 THE EFFICACY OF TRANEXAMIC ACID IN MINOR SURGERY WITH BLEEDING DISORDERS PATIENTS: 17 YEARS EXPERIENCE AT UNIVERSITY HOSPITAL
Authors: Al Jaouni S. , Farsi D. , Al Muhayawi S. 
Published: June 2019

Background:Tranexamic acid (TXA) is an antifibrinolytic agent commonly used to reduce blood loss in different medical disorders.Aims:To assess the efficacy and outcome to use TXA in dental work with patient with bleeding disorders at our institute over 17 years period.Methods:This is a retrospective study to assess the efficacy of the TXA in all dental works for patients with bleeding disorders treated at King Abdulaziz University Hospital (KAUH) at King Abdulaziz University, Jeddah, Kingdom of Saudi Arabia, between 2000‐2017, also to assess the requirements of transfusion after the procedures.Results:One hundred twenty one patients with bleeding disorders underwent dental and minor surgery over 17 years with patient age range 3‐46 years. Tropical oral TXA in majority of the cases only 5% used intravenous TXA in hospitalized patients. Less than 5% required transfusion after the procedures.Summary/Conclusion:Strong evidence supports the use of TXA in minor surgery with bleeding disorders in our institute over 17 years. Markedly decrease and minimize the need of transfusion after use TXA in dental works.
PB1856 HEPATITIS ASSOCIATED APLASTIC ANEMIA: ETIOLOGY, CLINICAL CHARACTERISTICS AND OUTCOME
Authors: Tüfekçi Ö. , Hekimci Özdemir H. , Malbora B. , Özbek N.Y. , Yaralı N. , Erdem A. , Evim M. , Baytan B. , Karapınar T. , Oymak Y. , Yılmaz S. , Yılmaz Karapınar D. 
Published: June 2019

Background:Hepatitis associated aplastic anemia (HAA); is a form of acquired aplastic anemia in which bone marrow failure develops after an acute attack of hepatitis. Aplastic anemia can also be seen after liver transplantation due to acute fulminant hepatitis.Aims:In this study, we aimed to define clinical and labarotory characteristics, possible causes, treatment strategies and and clinical outcome in patients with HAA.Methods:Seventeen children from six centers throughout Turkey were enrolled in the study. Clinical data were retrieved from the medical records.Results:The median age at time of diagnosis of acute hepatisis was 8.9 years (min: 5‐max:17).Search for etiology revealed highly positive CMV‐DNA in one patient and HCV‐RNA in one patient. One other patient was found to be positive for EBV, CMV and parvovirus DNA. Besides, one patient had the diagnosis of autoimmune hepatitis. The median time from diagnosis of hepatitis to diagnosis of aplastic anemia was 30 days (min:0‐max:322). Pancytopenia was simultaneously present in 5 out of 17 (29%) patients. Liver transplantation due to acute fulminant hepatitis was performed in 5 patients (29%). Aplastic anemia developed before liver transplantation in two patients and after liver transplantation in three patients. In terms of treatment for aplastic anemia; 8 patients (47%) received immunsuppressive treatment (IST) with anti‐thymocyte globulin and cyclosporine. HLA identical hematopetic stem cell transplantation (HSCT) was performed in 5 patients (29%). Two patients who received IST later underwent HSCT. The median time from diagnosis of AA to IST and HSCT were 45 days (min:1‐max:218) and 104 days (min:86‐max:1282), respectively. At the end; 9 out of 17 patients (52%) were alive, in remission and transfusion free. Those who were alive either received HSCT and/or IST, except one patient who received no treatment. Eight patients (48%) died mainly due to infectious causes.Summary/Conclusion:Although there have been limited number of patients in the present study, it was noteworthy that approximately one‐third of patients presented with pancytopenia at the time of diagnosis of hepatitis. Further research is needed to investigate the effect of some etiological agents on the clinical outcome. The loss of patients who did not undergo IST and HSCT revealed once again the importance of initiating IST at the appropriate time together with donor search for HSCT in this group of patients.
PB1869 PERSISTENT COMPLEMENT ACTIVATION IS PROVOKED BY IGG‐AGGREGATES IN A SUB‐POPULATION OF CHRONIC LYMPHOCYTIC LEUKEMIA PATIENTS
Authors: Michelis R. , Tadmor T. , Barhoum M. , Shehadeh M. , Shvidel L. , Aviv A. , Stemer G. , Dally N. , Rahimi‐Levene N. , Yuklea M. , Braester A. 
Published: June 2019

Background:Therapeutic monoclonal antibodies used in Chronic lymphocytic leukemia (CLL) act through complement‐mediated cytotoxicity and other mechanisms, and thus depend on the complement (C) availability and activity. Recently we showed abnormal Western analysis pattern of the C5 component in some CLL patients, that was associated with high basal levels of C activation markers, and decreased activity of the classical pathway (CP). We hypothesized that the CP may be constantly activated, and thus exhausted, in a sub‐group of CLL patients, identified by the abnormal appearance of C5.Aims:The aim was to study the circulating abnormal C5 and its association with the observed decrease in CP activity, and to search for potential CP‐activating factors in CLL plasma.Methods:Blood samples were collected from 40 naïve CLL patients and 15 normal controls (NC). Activities of the CP and of the CP C5‐convertase were studied. C5, C5a and C5b were studied by Western blot analysis. The presence of high molecular weight (HMW) protein complexes, such as IgM or hexameric‐IgG, as potential CP activators was assessed by sera fractionation (gel‐filtration chromatography) followed by C activation with the obtained HMW, and low molecular weight (LMW) fractions. The levels of IgM were measured. Data from patients with abnormal C5 was compared to normal NC subjects and to patients with normal C5.Results:In patients with abnormal C5, activities of the CP and of the CP C5‐convertase were decreased, compared to NC subjects and to patients with normal C5. The abnormal C5 was identified as a complex of immunoglobulin with C5a (Ig‐C5a). In agreement, the high levels of C activation markers showed negative and significant correlation with activity of the CP, but not with the alternative pathway. The data on C activation by the HMW fraction indicated the presence of IgG‐aggregates, and not IgM, as the C activating factor in sera.Summary/Conclusion:In some CLL patients, factors such as IgG‐aggregates that are present in sera constantly trigger the activation of the CP. This constant activation results in the release of activation products, such as C5a, that form the complex Ig‐C5a. Another result is the exhaustion of the CP and the inability to exert CP activity that is comparable to normal subjects. The data provides a potential prognostic tool that may personalize therapy by identifying a sub‐group of CLL patients who display Ig‐C5a and impaired CP activity, and are likely to be less responsive to immunotherapy due to compromised CP activity.
PB1873 PREDIAGNOSTIC TRAJECTORIES OF HEMOGLOBIN, LYMPHOCYTE AND PLATELET COUNT IN PATIENTS DEVELOPING CLL.
Authors: Andersen M. , Grand M. , Siersma V. , Andersen C. , Niemann C. 
Published: June 2019

Background:CLL is a slowly developing disease, but information about development in hemoglobin, platelet and lymnphocyte counts prior to CLL diagnosis is sparse and prediagnostic trajectories of such need exploring. A better understanding of disease progression will generate earlier treatment options and may even lead to preventive approaches. Despite general agreement that CLL patients have lymphocytosis in the years preceding a diagnosis, there is less certainty as to how why and when biomarkers develop. Therefore, we undertook a cohort study comparing hemoglobin, lymphocyte and platelet count trajectories in patients with CLL with unmutated IGHV (CLLunmut), mutated IGHV (CLLmut) compared with control individuals.Aims:To define how biomarker trajectories of patients with CLL differ from control individuals.Methods:All patients diagnosed with CLL in Greater Copenhagen between 2008 and 2016 were matched to 15 randomly selected control individuals matched on sex and age at diagnosis. We retrieved data on all CLL patients and their control individuals from the Copenhagen Primary Care Laboratory database, which contains results from all prediagnostic tests requested by general practitioners in Copenhagen from 2000 to 2015. We estimated the population‐averaged trajectories separately for each biomarker using generalized estimating equations. We included time to diagnosis, classification group (controls, IGHVunmut and IGHVmut), sex and age at diagnoses as covariates, along with an interaction between time to diagnosis and classification group.Results:Of the 778 patients who developed CLL, 437 were IGHVmut, 200 IGHVunmut and 141 patients had unknown IGHV status. We included 71.957 prediagnostic lymphocyte count measurements, 111.465 platelet count measurements, 107.029 CRP measurements and 111585 hemoglobin measurements. The lymphocyte‐count‐trajectories differed significantly between the IGHVmut and IGHVunmut subgroups. From 8 years prior to diagnosis, the IGHVmut subgroup had a slower increase from a higher starting point compared to the IGHVunmut subgroup, which increased closer to diagnosis with a steeper slope resulting in an overall higher lymphocyte count at time of diagnosis.Hemoglobin decreased linearly over time in all groups. In line with the findings for lymphocytosis, the platelet count decreased steadily from 8 years prior to diagnosis for patients with IGHVmut status, whereas the trajectories of IGHVunmut patients decreased dramatically 5 years prior to diagnosis for IGHVunmut patients.Summary/Conclusion:Here, we reveal that IGHVunmut patients develop lymphocytosis and thrombocytopenia within 5 years prior to diagnosis, much closer to diagnosis than IGHVmut patients do. By defining the time point of CLL development for these two disease entities, we identify the window of opportunity for population‐based studies to unravel the mechanisms of CLL progression, paving the road for personalized preventive interventions.image
PB1899 CONCEPTUAL MODEL OF CHRONIC LYMPHOCYTIC LEUKEMIA
Authors: Eek D. , Blowfield M. , Krogh C. , Chung H. , Eyre T.A. 
Published: June 2019

Background:A comprehensive conceptual model (CM) of chronic lymphocytic leukemia (CLL) is required to help researchers understand patients’ unmet needs and direct future advancements in the field, particularly in developing patient‐centered endpoints to evaluate the benefits of new therapies within clinical trials.Aims:The current study aimed to create a CM of disease‐ and treatment‐related signs, symptoms and impacts in patients with first‐line (1L) or relapsed/refractory (R/R) CLL.Methods:The CM was based on literature searches, review of CLL patient blogs/forums, interviews with expert hematologists, and semi‐structured concept elicitation interviews with 40 patients with CLL (20 1L, 20 R/R; with fatigue, weight loss, fever, and/or night sweats in previous week). To identify salient concepts, the number of patients mentioning each concept and the concept's mean disturbance rating (from 0 [not at all] to 10 [very]) were mapped.Results:Literature searches identified 32 prevalent concepts, with the most common being fatigue/tiredness. Patient blogs/forums revealed further symptoms (muscle/joint aches, headaches, weakness) and impacts (stress, fear of death, uncertainty). Clinicians reported recurrent infections and enlarged lymph nodes as key signs of CLL and noted that fatigue is related to both symptoms (e.g. tiredness) and impacts (e.g. needing to rest and limit daily activities). In patient interviews, 50 concepts were revealed, with 42 present in both 1L and R/R; fatigue was the most prominent and impactful. Fatigue‐related sub‐concepts were identified, covering symptoms (tiredness/need for sleep, lack of energy, weakness, cognitive fatigue) and impacts (decreased ability to maintain social/familial/professional role, decreased physical functioning, frustration). Three versions of the CM were created: an overall model with all identified concepts, and two models highlighting the most salient concepts in 1L and R/R (Figure 1). Muscle/joint aches, night sweats, bruising, fatigue‐related symptoms, fever and recurrent infections/illness were salient symptoms in both 1L and R/R. Salient impacts in both 1L and R/R were fatigue‐related impacts, insomnia, decreased cognitive/emotional functioning, anxiety/worry, stress, depression, financial difficulty, and fear of death. Dyspnea and cough were salient in 1L only, and enlarged lymph nodes, headaches, pain/discomfort, weight loss, nausea/vomiting, and infusion reactions were salient in R/R only.Summary/Conclusion:The three versions of the CM can help to inform patient‐centered endpoints to evaluate new treatments for 1L and/or R/R CLL.image
PB1915 CD14 AS A POTENTIAL PROGNOSTIC FACTOR AND BCL‐2 AS A THERAPEUTIC TARGET IN EGYPTIAN B‐CELL CHRONIC LYMPHOCYTIC LEUKEMIA PATIENTS
Authors: Elkhawanky M. , Morsy M. 
Published: June 2019

Please indicate where the abstract has been published before: Journal of Applied Hematology.Background:B‐cell chronic lymphocytic leukemia (B‐CLL) is a unique lymphoproliferative disorder that scarcely occurs under the age of 40. B‐CLL represents a neoplastic disorder caused primarily by defective programmed cell death and accompanied by a myriad of cellular and humoral immune defects.Aims:This study aimed to assess Bcl‐2 and CD14 expression in B‐CLL patients and their study as probable prognostic and therapy targeting factors.Methods:In this study, we assessed Bcl‐2 and cluster of differentiation (CD14) expression in a group of Egyptian patients with B‐CLL. Forty B‐CLL patients and 20 apparently healthy individuals served as the control group were included in this study.Results:Aberrant expression of Bcl‐2 protein appeared in all B‐CLL patients (100%). Bcl‐2 expression showed a highly positive correlation with total lymphocyte count and lymphocyte count (P = .000 for both) and a positive correlation with lactate dehydrogenase (P = 0.044). The expression of myelomonocytic antigen “CD14” above the cutoff value 5 × 109/L was reported in 70% (28/40) of B‐CLL patients, 55.6% (10/18) of the intermediate‐risk group, and 81.8% (18/22) of high‐risk group.Summary/Conclusion:There was a significant increase in Bcl‐2 protein and CD14 in B‐CLL patients. Bcl‐2 was highly increased in all patients and CD14 more observed in the high‐risk group than that of the intermediate risk group.