bluuebunny/crossref_metadata_2025_split huggingface dataset:
PB1782 TWO‐YEAR SURVIVAL WITH AXICABTAGENE CILOLEUCEL IN RELAPSED OR REFRACTORY LARGE B‐CELL LYMPHOMA: AN UPDATED ANALYSIS
Authors: Diakite I. , Lin V.W. , Klijn S. , Navale L. , Purdum A.G. , Fenwick E. , Botteman M. , van Hout B. 
Published: June 2019

Background:Relapsed/refractory large B cell lymphoma is historically associated with a poor prognosis, with a median overall survival (OS) of 6.3 months. In the 2‐year update of the ZUMA‐1 trial of axicabtagene ciloleucel (axi‐cel), median OS was not reached after a median follow‐up of 27.1 months. Prior analysis at 1‐year suggests that traditional parametric survival models cannot accurately estimate long‐term OS with axi‐cel when a large proportion of patients achieve durable remissions, thereby supporting the use of a mixture cure model (MCM) for survival extrapolations (Bansal, et al. Biol Blood Marrow Transplant. 2018).Aims:We analyzed the updated 2‐year ZUMA‐1 data to further explore the robustness of MCM.Methods:The ZUMA‐1 data were analyzed using a traditional parametric model, MCM, a general mixture model (GMM), and an integrated Markov cure model (IMCM). The MCM assumed patients with long‐term OS would have similar mortality as the age‐adjusted general population. The GMM relaxed this assumption by separately fitting and then combining parametric survival functions for poor‐ and good‐prognosis patients in a single survival function. The IMCM simultaneously accounted for OS and disease progression in a single framework. All parameters were estimated via maximum likelihood estimations, and model fit was assessed via Akaike information criterion (AIC).Results:The best‐fitting traditional model estimated a mean OS of 10.6 years (AIC = 444.3). The best‐fitting MCM estimated a mean OS of 13.5 years, with a 51.0% long‐term OS fraction (AIC = 439.3). The best‐fitting GMM produced a mean OS of 13.5 years, with a 52.7% long‐term OS fraction (AIC = 442.1). The best‐fitting IMCM estimated a mean OS of 13.4 years, with a 50.5% long‐term OS fraction (AIC = 916.6). The higher AIC for GMM and IMCM is partly because of specifying more parameters than MCM.Summary/Conclusion:Analyzing the updated ZUMA‐1 2‐year data, both the GMM and IMCM showed good model fit and results consistent with those of the MCM. These results support the long‐term survival associated with axi‐cel in relapsed/refractory large B cell lymphoma driven by the ≥ 50% long‐term OS rates.
PB1808 THE LEVELS OF SERUM FERRITIN CAN BE A PREDICTIVE FACTOR FOR SURVIVAL OUTCOMES IN DIFFUSE LARGE B CELL LYMPHOMA PATIENTS WITH ANEMIA
Authors: Lee H.S. , Jeong J.Y. , Jo J.‐C. , Lee W.S. , Lee J.H. 
Published: June 2019

Background:There are many clinical and molecular factors used to predict outcomes in patients with malignant lymphomas. Some studies have shown that serum ferritin levels correlated with tumor mass and closely followed disease activity in patients with hematologic malignancies such as malignant lymphoma and acute leukemia. And serum ferritin has frequently been used as a surrogate marker for systemic iron stores, but may also be elevated in specific circumstances without excess iron stores, such as in inflammation. Nevertheless, in actual clinical practice, the patients with malignant lymphoma, who are anemic and have high serum ferritin levels, are considered to suffer from anemia of chronic disease (ACD). To date, no studies have reported the survival differences between the ferritin and Hemoglobin (Hb) levels.Aims:Therefore, we investigated the clinical significance of high serum ferritin level in DLBCL patients with ACD.Methods:A total of 312 patients who were diagnosed with DLBCL between 2010 and 2016 were retrospectively analyzed. Patients were divided into four groups based on their ferritin (<500 and ≥500 ng/ml) and hemoglobin (Hb, <12 and ≥12 g/dL) levels. Progression free survival and Overall survival were calculated with the use of the Kaplan‐Meier methods.Results:In this study, several factors were demonstrated as independent prognostic factors for survival outcomes. IPI risk is an independent prognostic factor for the 5‐year PFS and 5‐year OS (relative risks (RR) = 0.458, 95% confidence interval [CI]: 0.277–0.758, p = 0.002 and RR = 0.297, 95% CI: 0.152–0.578, p < 0.001, respectively). Non‐bulky mass (<10 cm) (RR = 1.995, 95% CI: 1.140–3.448, p = 0.015) and female sex (RR = 1.848, 95% CI: 1.141–2.997, p = 0.013) were independent good prognostic factors for the 5‐year PFS. Low Hb and high ferritin were also independent poor prognostic factor for the 5‐year PFS (RR = 2.411, 95% CI: 1.063–5.473, p = 0.035: compared with high Hb and low ferritin levels and RR = 2.124, 95% CI: 1.072–4.209, p = 0.031: low Hb and low ferritin). Nevertheless, the groups based on Hb and ferritin levels did not significantly differ for 5‐year OS. In addition, the survival outcomes based on the ferritin level in patients with anemia (Hb < 12.0 g/dL) indicated statistically significant difference. The 5‐year PFS values were 59.3% and 40.9% in low and high serum ferritin levels (<500 and ≥500 ng/ml), respectively (p = 0.01), and the 5‐year OS values were 78.4% and 51.9% in the low and high ferritin levels, respectively (p = 0.006).Summary/Conclusion:High serum ferritin levels may prove to be efficient predictive markers for survival outcomes in DLBCL patients with anemia looks like ACD. In DLBCL patients with anemia, that is, considered as ACD, high ferritin level may not indicate a simple ACD but may be a prognostic factor for poor survival.
PB1834 PRALATREXATE EXPERIENCE IN NON HODGKIN LYMPHOMA
Authors: Enciso‐Olivera L. , Patiño B. , Diaz M. , Martinez H. , Otero D. , Spirko P. , Acon C. 
Published: June 2019

Please indicate where the abstract has been published before: Third National Congress of clinical investigation. Colombian Association of Oncology and Hematology (ACHO)Background:Pralatrexate is an antimetabolite used mainly in the treatment of relapsed or refractory peripheral T‐cell lymphoma. However, due to its low prevalence rate, and a small population analyzed in the trials, there is not a trial which evaluated results in ordinarily practice in our knowledge.Aims:To study the treatment with Pralatrexate in a 10 patients series with T‐cell lymphoma, both nodal and cutaneous, attended in our institution.Methods:Case series. Patients older than 18 years old, with a diagnosis of T‐Cell lymphoma, any subtype, treated with at least one cycle of Pralatrexate with available information for following up and treatment evaluation. All the analysis were made in the statistic package R (Version 3.4.3) and STATA 15.Results:Ten patients were included, 50% were men. The median was 47.8 years (IQR 17.04). The 50% had a Mycosis Fungoides (MF) diagnostic, being the most frequent histologic type. Five patients had the diagnosis of T Cell Lymphoma NOS which, one (10%) T cell Lymphoma ALK‐negative, one (10%) angioimmunoblastic lymphoma and one (10%) primary cutaneous anaplastic lymphoma.All the patients had received a prior treatment based on anthracyclines. The number of treatment received prior to the Pralatrexate beginning was a mean of 2,8 (SD 1.03). The 30% (three patients) suffered grade 3 mucositis in at least one cycle. Four patients required to be admitted at least in a cycle due to complications related to the treatment, and a patient required to be admitted in an intensive care unit requiring vasopressor support. None opportunistic infections were reported nor febrile neutropenia related to the other treatment cycles.A patient (10%) reached out complete response, two patients were in stable disease. Six patients (60%) progressed during the treatment after a mean of 2.8 cycles (1 to 4). At the last evaluation time, five (50%) of patients had started a new treatment line.Summary/Conclusion:The pralatrexate treatment in our patients with T cell lymphoma diagnosis offers a low response and short duration rates. Despite its good tolerance, also there is a high risk of complications, mainly mucositis.
PB1835 A PHASE 1/1B DOSE‐ESCALATION TRIAL EVALUATING CPI‐818, AN ORAL INTERLEUKIN‐2‐INDUCIBLE T‐CELL KINASE INHIBITOR, IN PATIENTS WITH RELAPSED/REFRACTORY T‐CELL LYMPHOMA
Authors: Mobasher M. , Miller R.A. , Janc J. , Kwei L. , Barker C. , Mohammady A. , Luciano G. , Khodadoust M. , Radeski D. , Horwitz S.M. , Kim Y.H. 
Published: June 2019

Background:Interleukin‐2‐Inducible T‐Cell Kinase (ITK) is a Tec‐family, non‐receptor tyrosine kinase expressed in T cells that plays a key role in T‐cell receptor (TCR) signaling, which is required for development of T‐cells. In T‐cell lymphoproliferative disorders, expression of the TCR and its downstream signaling components are maintained, which suggests that malignant cells may exploit this growth and survival pathway to their advantage. Professional antigen‐presenting cells abundant in the lymphoma microenvironment may provide antigen to drive TCR signaling through ITK, which is expressed in a variety of T‐cell lymphomas including PTCL, CTCL, ALCL, and in a subgroup of T‐lymphoblastic leukemia/lymphoma. CPI‐818 is a first‐in‐class, irreversible, covalent‐binding ITK inhibitor with a high degree of selectivity for ITK. By inhibiting ITK, CPI‐818 blocks signaling pathways that are essential to inflammatory responses and has shown to inhibit tumor growth in animal models.Aims:To test the effect of CPI‐818 clinically, a phase 1/1b dose‐escalation trial of CPI‐818 is initiated in subjects with relapsed/refractory T‐cell lymphoma.Methods:The trial will include patients with various types of T‐cell lymphoma (PTCL and CTCL) who have progressed on, refractory to, relapsed, or intolerant to at least 2 standard therapies; age ≥ 18 yo; have ECOG status 0‐1; adequate organ function; and without any other condition that would contraindicate the use of the investigational product. Dose Escalation with 3 + 3 (+ optional 3) design will consist of up to 6 ascending dose levels (100,200, 400, 600, 900, and 1200 mg BID) of CPI‐818. In the Dose Expansion phase, there will be 4 disease‐specific expansion cohorts (AITL, PTCL‐NOS, CTCL and other T‐cell lymphoma), and each cohort may enroll up to a maximum of 28 subjects/cohort based on a 2‐stage expansion design‐ Figure.The objectives of the study are to evaluate the safety and tolerability of CPI‐818; establish the maximum tolerated dose or the maximum administered dose of CPI‐818; evaluate pharmacokinetics and pharmacodynamics of CPI‐818 in humans; assess the anti‐tumor activity of CPI‐818 and identify potential biomarker signals. Study schema in the figure.Approximately 151 subjects will be enrolled at approximately 35 sites in the US, South Korea, and Australia.Results:None. Trial in progressSummary/Conclusion:None. Trial in progressimage
PB1838 EPISTAXIS IN PEDIATRIC TERTIARY OUT‐PATIENT CLINIC: COULD IT BE AN ALARMING SIGN?
Authors: Elalfy M. , Tantawy A. , Badr Eldin B.E. , Ebeid F. , Mekawy M.A. , Mohammad Y. 
Published: June 2019

Background:Epistaxis could be an alarming bell to diagnose a hemostatic disorder.Aims:To detect those with possible bleeding tendencies using simple tools of assessment.Methods:A prospective study for children attended tertiary pediatric out‐patient clinic (POPC) over a one year; who had been presented with epistaxis of non‐apparent cause. They underwent clinical assessment and parents answered pediatric bleeding questionnaire and epistaxis severity score. Complete blood count and coagulation profile, platelet function screening tests.Results:100 patients less than 18 years with epistaxis (53 females and 47 males), estimated annual frequency of epistaxis was 1 in 300 children attended Ain Shams University out‐patient clinic. Half of them were younger than six years. 76 had recurrent epistaxis and 12 had systemic comorbidities. 90% presented by anterior nasal bleeding and the majority had been controlled just by nasal compression. 43 patients presented with epistaxis only; 15% had definite local cause, 85% of them were considered idiopathic on initial evaluation. 57 presented with other bleeding manifestations; 82% of them had a definite hemostatic disorder and ten percent needed further assessment. There was a positive family history for epistaxis in half of those with definite hemostatic disorders. A bleeding score of ≥2 showed significant value in suspecting hereditary hemostatic disorder as a cause of epistaxis.Summary/Conclusion:Epistaxis as a presenting symptom to the POPC is not uncommon; the use of pediatric bleeding questionnaire was helpful to detect those with an underlying hemostatic disorder. Epistaxis was a presenting symptom for a hemostatic bleeding disorder in half of the referred cases. Still around 20% of epistaxis with suspected hemostatic disorder need further studies to reach a definite diagnosis.
PB1846 ANTHROPOMETRIC AND HORMONAL PARAMETERS IN COMPARISON WITH BONE MINERAL DENSITY IN MEN WITH HAEMOPHILIA FROM LOWER SILESIA ‐ PRELIMINARY REPORT
Authors: Biernat M.M. , Jędrzejuk D. , Urbaniak‐Kujda D. , Prajs I. , Podolak‐Dawidziak M. , Wróbel T. 
Published: June 2019

Background:In patients with haemophilia, recurrent episodes of bleeding lead to joint deterioration and bone resorption. To date, the effect of various risk factors on the bone mineral density (BMD) reduction have found conflicting results.Aims:The aim of the study was to analyze the impact of certain parameters, such as: viral status of patients, estradiol, testosteron, parathormone and vitamin D levels in relation to bone density.Methods:24 men with moderate and severe haemophilia, aged 18‐35 were enrolled. BMD at the lumbar spine, trabecular bone score (TBS) and total body densitometry were measured using dual X ray absorptiometry method (DXA) (densitometer Horizon, Hologic, 2017). Blood analyses were performed for morphology parameters, liver and kidney function parameters, HCV, HBV, HIV viral status, estradiol, testosteron, DHEA‐S, TSH, parathormone and Vitamin D levels.Results:The study population included 24 men with haemophilia A, who had been receiving prophylactic factor replacement therapy. HCV seropositivity was found in 6/24 patients (25%), whereas HBV seropositivity was detected in 4 patients (16,7%). There was no patient infected with HIV virus. No statistical correlation was found between BMD and viral serological status. It was found that in 15/24 patients BMD was normal with a Z‐score of > ‐1 (62,5%), whereas in 9/24 patients (37,55%), BMD was decreased. In hemophilic patients with normal BMD Z‐score, the increased BMI, androidal fat deposit (AFD), gynoidal fat deposit (GFD), fat mass index (FMI), free fat mass index (FFMI), Estimated visceral adipose tissue (Est VAT) mass were detected. Among all analyzed hormones, only serum estradiol concentration was statistically higher in patients with normal BMD. In 17/24 examined patients Vitamin D deficiency (<20 ng/ml) was detected (71%), although Vitamin D insufficiency (<30 ng/ml) was found in 4/24 patients (16,7%). Three patients (12,5%) had a normal Vitamin D concentration.Summary/Conclusion:The higher BMD in haemophilic patients is related with certain anthropometric parameters, such as body‐fat‐, free‐fat‐mass indexes and visceral fat tissue. BMD negatively correlated with % body fat, androidal fat mass and PTH, whereas TBS negatively related with androidal/visceral fat mass. We found that Vitamin D deficiency is very common in haemophilic patients, however there was no correlation between Vitamin D levels and BMD.
PB1883 GLYCOPROTEIN STRUCTURES OF LEUKEMIC B‐LYMPHOCYTES AND CD38 EXPRESSION IN CHRONIC LYMPHOCYTIC LEUKEMIA
Authors: Shalay O. , Lebed H. , Barilka V. , Zotova O. , Valchuk M. , Loginsky V. 
Published: June 2019

Background:Glycoprotein cell structures (glycocode) play an important part in intercellular interaction. Changes in their structure may determine the ability of leukemic cells to spread (expansion), and impact the exposure of membrane antigen, which transmit pro‐ and antiapoptotic signals.Aims:The aim of this study was to conduct research of leukemic lymphocytes glycocode in chronic lymphocytic leukemia (CLL) and its interconnection with the expression of prognostically significant CD38 antigen.Methods:Carbohydrate determinants of leukemic lymphocyte membrane were studied in 65 CLL patients using panel of 12 lectins with main carbohydrate specificity, and CD38 expression.Results:27% of lymphocytes of CLL patients were identified as containing Thomsen–Friedenreich antigen (PNA+), absent in normal lymphocytes. Leukemic lymphocytes are characterized by a significantly lower level of I and II type N‐glycans’ glycosidic chains (RCA). The lymphocytes of the CLL patients reacted weaker with GalNAca‐specific SBA lectin, Mana‐specific PSL lectin and GlcNAcb‐specific lectins (WGA і STL), polyspecific lectin PHA.We researched the correlation between lectin receptors expression level and CD38 antigen. The patients were divided into groups with low and increased antigen expression level. In the low CD38 expression level group (≤30%) no statistically significant changes in interaction with lectins were detected as compared to the general patients group. Leukemic lymphocytes with increased CD 38 expression (>30% CD38+ cells) exhibit a significantly higher interaction level with PNA lectin (T antigen) and decreased interaction level with RCA; they have more terminal Fucα residues (H antigen, LAL lectin).A correlation analysis has been done between the percentage of leukemic cells that bind lectins and the number of CD38+ lymphocytes. A high level of CD38 expression correlates with increased A antigen disaccharide content (GalNAAcα1→3Galβ; SBA lectin), decrease of GlcNAcβ sialylated residues (WGA lectin, r = –0,702; STL lectin, r = –0,503), and sialic acid (SNL lectin). They have less polyantennae N‐glycans (PHA lectin, r = –0,701).Summary/Conclusion:A higher CD 38 expression level is accompanied with an increased number of cells containing Thomsen‐Friedenreich antigen (PNA lectin) and corelates positively with antigen A level (SBA lectin) and terminal Fucα (LAL lectin) and a decreased level of Galβ glycosidic residues (RCA lectin); it correlates negatively with a decrease of GlcNAcβ sialylated residues (WGA, STL lectin), and residues of neuraminic acid (NANA, SNL lectin) and polyantennae N‐glycans (PHA‐L lectin).
PB1907 IBRUTINIB THERAPY IS ASSOCIATED WITH SERIOUS INFECTIONS IN PATIENTS WITH B‐CELL MALIGNANCIES ‐ A SINGLE CENTER EXPERIENCE
Authors: Misura Jakobac K. , Milunovic V. , Kursar M. , Mandac Rogulj I. , Ostojic Kolonic S. , Radic‐Kristo D. 
Published: June 2019

Background:Ibrutinib is an irreversible inhibitor of Bruton tyrosine kinase (BTK). Recently, ibrutinib has become available in Croatia for chronic lymphocytic leukemia (CLL) with del17p aberration or in early relapse and for relapsed/refractory mantle cell lymphoma (MCL) pretreated with bendamustine and rituximab. BTK inhibition can lead to immunosuppression through B‐ and T‐cell inhibition resulting in an increase in infections. In literature, systematic meta‐analyses have shown higher incidence of infections in B‐cell malignancies treated with ibrutinib, however the results for CLL are diverse.Aims:The main aim of this retrospective study was to retrospectively review all infections associated with ibrutinib in patients treated with B‐cell malignancies and characterized the grade and possible predisposing factors at single center institution.Methods:We retrospectively reviewed the medical charts for all patients treated with ibrutinib in era from 2015‐2018 to estimate the rate and grade of infections and possibly underlying factors predisposing these patients to infections.Results:A total number of patients included was 32, mainly the patients treated for CLL (28). Median line of previous therapies was 2 with only two patients being treatment naïve. The dosage of ibrutinib was according to the standard of care with median exposure to ibrutinib being 8.5 months. Any grade of infections occurred in 41.9% (N = 18) of our sample with median time to first infection being 82.5 days. The most common type of infection was sepsis (33.3%) followed by pneumonia (22.2%). The specific microbiological agents were isolated in 8 patients. Most of infections were mild (grade I/II according to NCI CTCAE nomenclature) estimated to be 41.2% in our sample. Grade III‐IV infections occurred in 35.3% of sample and grade V infections occurred in 4 patients. It is important to note that re‐infection occurred in 4 patients. Ibrutinib therapy was temporally withdrawn in 9 patients with median time off therapy being 30 days while it was discontinued indefinitely due to infection in 3 patients. Previous fludarabine therapy (p = 0.024) was the only factor associated with the occurrence of infection unlike previous number of therapy, neutropenia, leukopenia and levels of immunoglobulin G. In survival analysis, infections in general were not associated with poorer outcome (p = 0.265), but the grade of infection was associated with poorer outcome (p = 0.003)Summary/Conclusion:Our findings show, however, higher grade of serious infections than pivotal RESONATE trial with expected incidence early in the treatment course. The role of temporary ibrutinib withdrawal due to an infection should be explored in the greater samples possible through the larger observational studies.
PB1921 COMPREHENSIVE ANALYSIS OF MOLECULAR RESPONSE IN TUNISIAN CML PATIENTS FOR TREATMENT DISCONTINUATION
Authors: Frikha R. , Elloumi M. , Kamoun H. 
Published: June 2019

Background:Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm characterized by a balanced genetic translocation, t(9;22)(q34;q11.2) and the generation of a BCR‐ABL1 fusion oncogene. Assessment and monitoring of BCR‐ABL1 levels by quantitative PCR (qPCR) is essential for the management of CML patients treated with TKIs.Currently, deeper molecular response (DMR: BCR‐ABL1 ≤0,01% IS) is considered to be the gateway to treatment‐free remission, which is becoming a high‐priority goal of CML treatment. Thus, achieving deep molecular response is a requirement for a successful treatment discontinuation.Aims:This study was carried out to identify patients with chronic myeloid leukemia (CML) treated with TKI therapy in routine clinical practice in Tunisia potentially eligible for treatment discontinuation, based on a molecular response (MR) on the international scale (IS).Methods:It was a 2 years retrospective study of 114 CML patients who attended the hematology department at the Hospital University of Sfax, south of Tunisia. Quantitative assessment of the BCR‐ABL transcript was performed using the Cepheid Xpert BCR‐ABL ultra assay.Results:Most patients (67,5% i.e 77/114) had an optimal response according to the European LeukemiaNet 2013 guidelines. Among them; 58,4% were in deep molecular response at their last visit and had been receiving TKI for at least 4 years.Summary/Conclusion:Despite the limit of our study, the available real‐life molecular responses with TKI therapy should be considered to identify potentially CML patients eligible for discontinuation of TKI therapy.