bluuebunny/crossref_metadata_2025_split huggingface dataset:
PB1909 HYPOGAMMAGLOBULINEMIA AS A PREDICTOR OF SURVIVAL IN OLDER PATIENTS WITH CHRONIC LYMPHOCYTIC LEUKEMIA
Authors: Umit E. , Baysal M. , Bas V. , Gulsaran S. , Demirci U. , Kirkizlar O. , Demir A.M. 
Published: June 2019

Background:chronic lymphocytic leukemia (CLL) is the most frequent leukemia of adults and has a median age of 71 years at diagnosis. Approach to CLL patients may include watchful waiting as well as chemotherapy and recently, immunotherapy and small molecules. As life expectancy in general population increases, a significant increase in patients who are accepted as old is also expected. As fitness is not a simple concept, explained with chronological age alone, older patients are suggested to be assessed individually and thoroughly in terms of cognition, comorbidity and mental health.Aims:We aimed to investigate the factors which may be related with survival and should be improved in older patients with CLL.Methods:104 patients who were 65 years and older diagnosed and treated for CLL were enrolled in the study in a retrospective manner. Demographic and survival data were recorded from files.Results:Mean age of our patients was 76,69 years (65‐91). 45 patients were female (43,3%) while 59 were male (56,7%). Median duration of watchful waiting period was 18 months (0‐74). 13 patients were Rai Stage 0 (12,5%) while 36 were Stage I (34,6%), 40 were Stage II (38,5%), 5 were Stage III (4,8%) and 10 were Stage IV (9,6%). Median lymphocyte count was 19.750/μL, median hemoglobin level 12,7 g/dL and median platelet count was 193 x106/L.Median survival was 46 months (2‐86 months). 40 patients had hypogammaglobulinemia (38,5%). 23 patients have developed a secondary malignancy (22,1%). 40 patients had immune thrombocytopenia (ITP) (38,5%) and 5 patients had autoimmune hemolytic anemia (AHA)(4,8%).Regarding the relation of complications during the course of disease, only hypogammaglobulinemia was observed to be related with survival. In patients who had hypogammaglobulinemia, mean survival was 42,25 months while in patients who did not have hypogammaglobulinemia, mean survival was 61,3 months (p < 0,05).Summary/Conclusion:Hypogammaglobulinemia should be sought in every older CLL patient and be supported if found. Survival of patients who have hypogammaglobulinemia is shorter, which may be explained with increased rates of infections as well as secondary malignancies due to the immune compromisation status.
PB1912 EFFICACY AND SAFETY OF RITUXIMAB BIOSIMILAR TRUXIMA IN PATIENTS WITH CHRONIC LYMPHOCYTIC LEUKEMIA AND NON‐HODGKIN'S LYMPHOMAS
Authors: Micheva I. , Useir S. , Gercheva L. 
Published: June 2019

Background:Rituximab, an anti‐CD20 monoclonal antibody, is a key therapeutic in the treatment of B cell lymphomas and Chronic lymphocytic leukemia (CLL). TruximaTMis the first biosimilar of the medicine Rituximab to be approved for the treatment of patients non‐Hodgkin's lymphoma (NHL) and CLL, showing similar efficacy, pharmacokinetics, safety and immunogenicity profile. The use of biosimilars may reduce treatment costs andincrease patient access to Rtuximab.Aims:The aim of the study was to assess the efficacy and safety of TruximaTM treatment in combination with chemotherapy in patients NHL and CLL followed for 12 months.Methods:A total of fifty one patients, 28 men and 23 women, were treated with ruximaTMin the Clinic of Hematology at “Sveta Marina” University Hospital, Varna. TruximaTMwas applied at a dose of 375 mg/m2every 3 weeks in combination with chemotherapy. Response was estimated at treatment completion.Results:Median age was 68,5 years. 22 patients were with CLL, one Richter,s syndrome, 16 with Diffuse large B cell lymphoma (DLBCL), 4 with Mantel cell lymphoma (MCL), 4 with Ssmall cell lymphoma (SCL), 4 with Marginal cell lymphoma (MZL). TruximaTMwas combined with different chemotherapeutic regimens: CHOP in 11 patients, Bendamustin in 23, FC in 6, MINE in 3, ACVBP in 1, COP in 3, ICE in 1, and Leukeran in 1. In 34 patients TruximaTMwas applied as a first line treatment, in 12 patients as a second line, in 5 cases as a third line. 30 patients have completed their treatment at the time of analysis. Complete response was achieved in 9 (30%) patients, partial response in 17 (56,7%) patients, stable disease in 4 (13,3%). Progressive disease was observed in 1 patient with DLBCL. Grade 3 or 4 hematological toxicity was registered in 5 patients (9,8%). Infusion related reactions were observed in 5,8% of the patientsat grade 1 and 2.Summary/Conclusion:Our experience with the biosimilar over the last year has revealed that TruximaTM is an effective treatment without unexpected side effects. Moreover, cost may be a factor for doctor's choice.
PB1922 PONATINIB INDUCES A SUSTAINED DEEP MOLECULAR RESPONSE IN A CHRONIC MYELOID LEUKAEMIA PATIENT WITH AN EARLY RELAPSE WITH A T315I MUTATION FOLLOWING ALLOGENEIC HEMATOPOIETIC STEM CELL TRANSPLANTATION
Authors: Cerveira N. , Ferreira R.B. , Bizarro S. , Correira C. , Torres L. , Lisboa S. , Vieira J. , Santos R. , Campilho F. , Pinho Vaz C. , Leite L. , Teixeira M. , Campos A. 
Published: June 2019

Please indicate where the abstract has been published before: BMC Cancer.Background:Atypical BCR‐ABL1 transcripts are detected in less than 5% of patients diagnosed with chronic myeloid leukaemia (CML), of which e19a2 is the most frequently observed, with breakpoints in the micro breakpoint cluster region (μ‐BCR) and coding for the p230 BCR‐ABL1 protein. p230 CML is associated with various clinical presentations and courses with variable responses to first‐line imatinib.Aims:In the present study we describe in detail the clinical history of a CML patient with a rare e19a2 BCR‐ABL1 transcript who has failed several lines of targeted therapy with tyrosine kinase inhibitors and relapsed after allogeneic hematopoietic stem cell transplantation.Methods:Detailed characterization of the patient's clinical history including therapeutic approach and cytogenetic and molecular analysis.Results:Here we report a case a CML patient with imatinib resistance due to an E255 V mutation, followed by an early post‐transplant relapse with a T315I mutation that achieved a persistent negative deep molecular response (MR5.0) after treatment with single‐agent ponatinib. Using CastPCR, we could trace back the presence of the T315I mutation to all the RNA samples up to the detection of T315 mutation by Sanger sequencing shortly after allogeneic hematopoietic stem cell transplantation.Summary/Conclusion:This case illustrates the major interest of Ponatinib as a valid treatment option for e19a2 CML patients who present a T315I mutation following relapse after allogeneic hematopoietic stem cell transplantation.image
PB1931 CARDIO‐ONCOLOGY UNIT IMPROVE THE MANAGEMENT OF TREATMENT WITH TKIS OF CHRONIC MYELOID LEUKEMIA PATIENTS: A SINGLE CENTER EXPERIENCE.
Authors: Spinosa G. , CAPALBO S.F. , CASAVECCHIA G. , ZICCHINO S. , DEL MASTRO M. , BRUNETTI N.D. 
Published: June 2019

Background:Although Tyrosine Kinase Inhibitors (TKIs) have revolutionated the treatment of Chronic Myeloid Leukemia (CML), it is importat to focus the attention about the safety of this class of drugs specially for cardiovascular adverse events (CVE), their “off‐ target” effects encompass a wide range of cardio toxicities, including left ventricular disfunction, electrocardiographic abnormalities with dysrhythmias, hypertension, myocardial ischemia and thromboembolic events. The long‐term safety call for a multidisciplinary effort embracing hematologists, cadiologists, nurses.Aims:demonstrate the usefulness of a cardio‐oncology unit in primary and secondary cardiovascular risk prevention in patients with chronic myeloid leukemia in treatment with TKIsMethods:From February 2005 to September 2018, 61 consecutive patients (27 women and 34 men) affected by CML were treated with TKIs at our institution. The patients underwent to clinical, laboratory and instrumental evaluations. Several informations about cardiovascular risk factors, lifestyle and concomitant medications, were collected with the support of a nurse, who administered to patients specific questionnaires. Patients were assessed at baseline and during follow‐up.Results:50% of patients already had cardiovascular disease at diagnosis, 35% of patients developed cardiovascular events during treatment.16.6 % of patients presented risk factors unchangeable, while 83.4 % of patients presented risk factors related to incorrect lifestyle habits.Before the intervention by cardio‐oncology unit, 65% of patients thought they knew the risks associated with the wrong lifestyle habits. After the intervention, the percentage of patients aware of the risk factors was 90% (p value <0.05: significance index). The therapeutic education program was considered very useful for this purpose by 95% of patients. 75% of patients said that their quality of life has improved during the observation period.Summary/Conclusion:CONCLUSIONS: In our institution, the Cardio‐oncology Unit deals with primary prevention and the secondary treatmet of cardiovascular disease therapy‐related. Our results confirm that a cardio‐oncology program applied to patients with CML can represent unique oppotunities and challenges to preserve cardiovascular health, to allow the timely delivery of cancer therapy and achieve disease free remission. Managment of treatment with TKIs of CML patients is multifaced and involve lifestyle education, pharmacotherapy, enhanced cardiovascular surveillance and support services.The optimal composition of cardio‐oncology team should involve support from cardiologist, oncologist and nurses.
PB1938 PERSPECTIVE OF THE PATIENT WITH CML AND FAILURE TO TREATMENT WITH IMATINIB AT AN ENVIROMENT OF LIMITED RESOURCES.
Authors: Osorno‐Rodríguez K.L. , Cantú‐Rodriguez O.G. , Gómez‐Villarreal J.P. , Ríos‐Rodelo M.R. , Lafarga‐Amao B. , Hawing‐Zárate J.Á. , Villalobos‐Gutiérrez L.E. , Gómez‐Almaguer D. 
Published: June 2019

Background:Chronic myeloid leukemia (CML) is a haematological malignancy caused by translocation t(9;22). The advent of imatinib meant a substantial improvement in the survival of patients compared to older therapeutic options such as busulfan, hidroxyurea and alfa interferon. The presence of resistance or failure to treatment to imatinib requires second‐line drugs such as dasatinib or nilotinib, however its correct access to the population with limited resources is restricted mainly by their costs.Aims:Evaluate the behavior and outcome of patients with a loss of response to imatinib who do not have access opportunately to a second of third line tyrosine kinase inhibitor (TKI).Methods:It's a retrospective, observational, longitudinal study of two medical centers. We collected all the demographic data and the laboratory values of the patients older than 18 years with a diagnosis of CML with failure to imatinib as well as its clinical evolution and the therapeutic measures taken.Results:We obtained the data from 139 patients attended between 2007 and 2018. The median age was 48 years (38‐59) in which 51.8% were males. 64.7% (90) has access to second‐line TKI in a timely manner with a median time between the loss of response and the start of the second‐line therapy of 3 months.In the group without timely manner access, in 57.1% of the patients, the imatinib dose was increased, 14.3% continued imatinib at the same dose due to preservation of hematological response, 22.4% had Ara‐C and/or alfa interferon added to them therapeutic scheme and 18.3% entered to a clinical trial after which 81.2% continued in molecular failure. Of these patients, 44.9% had late access to a second‐line TKI with a median time of 29 months (15‐53), 10.8% developed blastic crises, and 10.2% underwent an allogeneic bone marrowa transplantion, of this subgroup currently 6.1% are in hematological failure and 26.5% are in molecular failure.Of the group with timely access, 39% went to a third‐line TKI due to los of response to treatment, 6.7% developed blastic crises and 4.4% underwent allogeneic bone marrow transplantation, of this group currently 2.2% are in hematological failure and 10% are in molecular failure.Summary/Conclusion:In a population of limited resources such as ours, due to the lack of timely access to second‐line TKI as estabished by international guidelines, other options such as haematopoietic cell transplantation should be considered, in order to limit the risks that delaying the access to a second‐line TKI can cause.
PB1949 CHRONIC MYELOID LEUKEMIA PATIENTS WITH BOTH HIGH TH1 AND HIGH CD8+ T‐CELL LEVELS SHOW THE BETTER REMISSION, AND THE GOOD THERAPEUTIC RESPONSE ACCOMPANIES WITH THE HIGHER TH1 LEVEL
Authors: Dai J. , Yang X. , Wei Q. , Zou M. , Wang Y. , Li H. , Huang X. , Wang X. 
Published: June 2019

Background:The immune mornitoring on chronic myeloid leulemia (CML) patients may provide valuable guidence for the therapeutic strategies and prognosis prediction of this hematological malignancy.Aims:To investigate the correlation of Th1 and CD8+T‐based immunological characteristics of CML patients with the clinical efficacy.Methods:To analyze the Th1 proportion (Th1/CD4+T) and the CD8+T proportion (CD8+T/Lymphocyte) in the peripheral blood of all the CML patients diagnosed in our center. And the remission status at the same timepoint of the blood test are evaluated. The data is further statistically analyzed in different groups.Results:70% of the patients in newly‐diagnosed group (n = 10), 15.38% of the patients in complete cytogenetic response(CCyR) group (n = 13) and 15.15% of the patients in molecular response 4.5(MR4.5) group (n = 67) respectively show a Th1 level below the lower limit of normal, therefore, the low‐Th1 percentage of the newly‐diagnosed group is significantly higher than that of the CCyR group and that of the MR4.5group (P = 0.01; P = 0.00). On the other hand, the average of the actual Th1 value in the newly‐diagnosed group is also significantly lower than that in the CCyR group and that in the MR4.5 group (P = 0.01; P = 0.00). As we have observed in clinic work that those patients with both high‐Th1 and high‐CD8+T levels (both higher than the upper limit of normal) mostly obtain better remission situations, furthermore, we analyze the relevant groups of CML patients statistically in this study. The results show: The MR4.5 rate in the high‐Th1 and high‐CD8+T group (n = 15) is significantly higher than that in the high‐Th1 and not‐high‐CD8+T group (n = 17) (P = 0.03), while the un‐remission rate in these two groups doesn’t show a statistically significant difference (P = 0.74). On the other hand, the MR4.5 rate in the high‐Th1 and high‐CD8+T group is also significantly higher than that in the low‐Th1 and high‐CD8+T group (here “low‐Th1” represents that the Th1 level is below the lower limit of normal; n = 10) (P = 0.00), while the un‐remission rate in the high‐Th1 and high‐CD8+T group is significantly lower than that in the low‐Th1 and high‐CD8+T group (P = 0.00).Summary/Conclusion:The good therapeutic efficacy of CML patients after treatment shows a significantly higher Th1 level compared with the level at diagnosis. And those patients with a Th1 level and a CD8+T level both higher than the upper limit of normal show the higher remission rate and the deeper remission level.
PB1953 QUALITY OF LIFE AND SYMPTOM BURDEN WITH FIRST AND SECOND GENERATION TYROSINE KINASE INHIBITORS IN PATIENTS WITH CHRONIC MYELOID LEUKEMIA
Authors: Toptas T. , Bostan H. , Kut K. , Pepedil Tanrikulu F. , Yilmaz F. , Atagunduz I. , Tuglular T. 
Published: June 2019

Background:With the advent of tyrosine kinase inhibitors (TKIs), patients with chronic myeloid leukemia (CML) have a life expectancy similar to those of age‐ and sex‐matched healthy population. Nevertheless, patients receiving TKIs report chronic adverse events, some of which may be associated with severe symptoms including fatigue, edema, muscle cramps. Additionally, generic imatinib has license in various countries. In retrospective analyses and post‐marketing safety monitorization, it seems to have a similar efficacy and safety profile. However, quality of life and symptom burden issues in patients receiving TKIs still remains to be elucidatedAims:We aimed to assess the quality of life and symptom burden in patients receiving original imatinib, generic imatinib, dasatinib, and nilotinib.Methods:A total of 121 patients with CML who have been receiving any TKI for at least three months was contacted either by phone or at their routine outpatient clinic visits. All patients accepted to be included in the study. Their demographic data were recruited from chart files. Quality of life was assessed by EORTC‐QLQ‐C30 and its CML24 module. Symptom burden was assessed by MD Anderson Symptom Inventory (MDASI). Questionnaire scores were calculated per associated protocols. Group comparisons were made by Kruskal Wallis test.Results:Median age of patient population was 53 (28‐90) years. Fifty‐four (44.6%) was female. Eighty‐three patients (81.4%) had Sokal low‐intermediate disease. Most of the patients had good ECOG performance status (<2: 96%) and low hematopoietic cell transplantation‐comorbidity index score (<3: 90.8%). Median duration of TKIs was 31 (3‐154) months. Ninety‐eight patients (86.7%) had major molecular response at the time of questionnaire. Patients receiving different TKIs had comparable quality of life and treatment‐related symptom burden scores (table and figure).Summary/Conclusion:First and second generation TKIs as well as generic imatinib have similar impact on quality of life. Although these molecules have different safety profiles, severity of treatment‐related adverse events are generally mild.image
PB1959 THE ROLE OF FLOW CYTOMETRY IN DIFFERENTIAL DIAGNOSIS OF CMML AND REACTIVE MONOCYTOSIS. THE LIPID SIGNAL PATHWAY CHARACTERISTICS IN CLONAL MONOCYTOSIS
Authors: Sevoyan A. , Sevoyan A. 
Published: June 2019

Background:Myelodysplastic syndrome (MDS) is a heterogeneous group of diseases characterized by ineffective erythropoiesis and dysplasia. MDS and its subtype CMML is highly associated with chronic inflammatory and autoimmune diseases; however the combination of MDS with other bone marrow neoplasms is not a common entity. Only few cases of MDS combined with other blood malignancies have been described. The pathogenesis and mechanisms of two different clones evolution in MDS is an unclear multistep process involving molecular genetic instability, epigenetic factors and innate immune response deregulation. The role of plasma lipid signaling pathway have been also defined in recent years.Aims:Is to investigate the role of immunophenotyping in differential diagnosis of CMML and reactive monocytosis and clarify the possible significance of phosphoinositides in diagnosis of CMML.Methods:Blood samples of patient with CMML combined with plasma cell disorder, patient with CMML and blood samples of 2 patients with monocytosis were examined in our laboratory. Peripheral blood CBC, bone marrow smear cytological examination, pathohistology, flow cytometry and PCR were performed for the diagnostic purposes. In parallel with classic diagnostic work‐up the chromatograph method was used to investigate the cytoplasmatic mono and di‐phosphoinositides in patients with CMML.Results:CBC reveal monocytosis >1000 less than 1 month duration, PCR analysis were negative for BCR ABL in all 4 cases. Case N = 1 histology examination Results: >30% of plasma cells express CD56 and CD138, atypical cells express MPO and CD14 and epithelioid granulomas. In case N = 1 Immuntophenotype results were the following: (CD64+)‐52%, (CD16+)‐44%, (CD14‐). In case N = 2 the dysplasia, megakaryocytes and monocytes were observed by histology examination. Immunophenotype Results: (CD14+/CD16)‐31.1%, (CD14+/‐CD16+)‐49.3%, (CD14‐/CD16‐)‐4.3%. There were monocytosis and secondary changes of hematopoietic tissue in histology examination of cases N = 3 and N = 4. Immunophenotype showed: (CD14‐/16‐)‐13%, (CD64+)15%, (CD56‐)‐3%. High level of mono and di‐phosphoinositides were registered in first 2 cases in compare with cases N3 and N4. The flow cytometry revealed monocyte specific markers in all 4 cases with certain variations.Summary/Conclusion:The exact immunophenotype markers for clonal monocytosis must be defined. Lipid signaling pathway components, such as cytoplasmatic mono and di‐phosphoinositides must be investigated in the context of clonal monocytosis and diagnostic purposes.
PB1968 TWO NEW MUTATIONS AND MOLECULAR CHARACTERIZATION OF G6PD GENE AMONG THAI CHILDREN WITH G6PD DEFICIENCY
Authors: Traivaree C. , Boonyawat B. , Photi‐a A. , Monsereenusorn C. , Phetthong T. 
Published: June 2019

Background:Glucose‐6‐phosphate dehydrogenase (G6PD) deficiency is the most common X‐linked inherited erythroenzymopathy in Thailand. The clinical and hematological manifestations of G6PD deficiency is variable.Aims:This study aimed to characterize the spectrum of G6PD gene mutations in Thai pediatric patients who were followed‐up in Phramongkutklao Hospital, a tertiary center in central Thailand.Methods:A total of 102 children including 73 males (71.6%) and 29 females (28.4%) were included in our study. Mutation analysis was performed by direct DNA sequencing of the G6PD gene. Neonatal hyperbilirubinemia was the most common (87.3%) clinical manifestation in this study.Results:Molecular analysis of G6PD gene in 102 G6PD‐deficient Thai children identified a total of 12 mutational types. G6PD Viangchan (871G>A) was the most common (46.2%) identified mutation. G6PD Canton (1376G > T) was the second most common and was identified in 15.4%, followed by G6PD Kaiping (1388G > A) 14.4% and G6PD Mahidol (487G > A) 8.6%, respectively. Eight uncommon G6PD mutations including G6PD Quing Yan (392G > T) (3.8%), G6PD Aures (143C > T) (1.9%), G6PD Coimbra (592C > T) (1.9%), G6PD Songklanagarind (196T > A) (1.9%), G6PD Union (1360C > T) (1.9%), G6PD Valladolid (406C > T) (1.9%), G6PD Chinese‐5 (1024C > T) (1%) and G6PD Mediterranean (563C > T) (1%) were identified in this study. G6PD Valladolid and G6PD Aures were firstly identified in Thai populations.Summary/Conclusion:This study characterizes the molecular heterogeneity of G6PD variants causing G6PD deficiency in Thai children. Our study demonstrated the efficiency of direct DNA sequencing which can identify mutations in all 102 patients.