bluuebunny/crossref_metadata_2025_split huggingface dataset:
PF650 AGE DOES NOT CONFER DIFFERENT FEATURES AND OUTCOMES IN PATIENTS WITH NEWLY DIAGNOSED ACTIVE MULTIPLE MYELOMA YOUNGER THAN 66 YEARS OF AGE TREATED IN A RECENT PERIOD
Authors: Bove V. , Ranero S. , Villano F. , Riva E. 
Published: June 2019

Background:Multiple myeloma (MM) is a disease of the elderly, with median age at diagnosis of 66 years. However, 10% of patients are younger than 50 years. Publications regarding age as prognostic factor for clinical characteristics at diagnosis and outcomes are heterogeneous, with some authors reporting aggressive presentation and worse outcomes in young patients and others showing better outcomes.Aims:To describe clinical and laboratory characteristics, response to treatment and survival in active newly‐diagnosed MM (NDMM) under 66 years. To compare outcomes between <51 and 51–65 years of age.Methods:Retrospective review of medical records of active MM diagnosed from jan2010 to dec2018 at Hospital de Clínicas, Montevideo, Uruguay. Smoldering MM and plasma cell leukemia were excluded. Characteristics at diagnosis were analyzed using descriptive statistics. Survival outcomes were calculated by Kaplan‐Meier method and compared using log‐rank test. In all cases, p < 0,05 was considered significant.Results:131 patients <66 years were included, 36 (27.5%) <51 years. Characteristics at diagnosis are shown in Table 1. Most patients were diagnosed at an advanced Durie‐Salmon and prognostic score (ISS) stages, showing no differences according to age. The mean monoclonal protein was lower in younger patients (p = 0,048). CRAB features and bone marrow infiltration were comparable. Bone plasmacytomas and extramedullary infiltration were more frequent in younger patients. Most used induction regimens were CyBorD and CTD in both groups. Rates of upfront autologous stem cell transplant (ASCT) consolidation were similar. Overall response rate (> = PR [partial remission]) was 77,4% in <51 and 79,9% in 51–65 years (p = 0,590) with comparable depth of response. Median progression free survival (PFS) was 25 months in <51 years and 26 months in 51–65 years (p = 0,683). Mortality rate was 33.3% in <51 years and 31.5% in older. The main causes of death were progression (53,2%) and infections 14,9%, similar in both groups. With a median follow up of 34 months, overall survival (OS) was 68,1%, median not reached in patients <51 years and 75 months in patients 51 – 65 years (p = 0,528).Summary/Conclusion:Clinical and laboratory features are similar in NDMM patients <50 and 51–65 years, although bone plasmacytoma and extramedullary disease were more frequent in the younger. However, this finding did not translate into differences in response or survival. Despite its efficacy and availability, upfront ASCT rate is low.imageDisclosures: no conflicts of interest to declare.Funding: none.
PF651 POMALIDOMIDE, CYCLOPHOSPHAMIDE AND DEXAMETHASONE IN RELAPSED/REFRACTORY MULTIPLE MYELOMA PATIENTS IN A REAL LIFE SETTING: A SINGLE CENTER RETROSPECTIVE STUDY
Authors: Trudel S. , Tessoulin B. , Jullien M. , Blin N. , Gastinne T. , Mahé B. , Dubruille V. , Bonnet A. , Lok A. , Chevallier P. , Peterlin P. , Garnier A. , Guillaume T. , Le Bourgeois A. , Le Gouill S. , Moreau P. , Touzeau C. 
Published: June 2019

Background:Pomalidomide dexamethasone (Pd) is a standard of care for relapsed and refractory multiple myeloma (RRMM) patients who received at least two prior lines of therapy, including both lenalidomide and proteasome inhibitor (PI). In the phase 3 trial MM‐003, patients randomized in the Pd arm achieved an overall response rate (ORR) of 31% and a median progression‐free‐survival (PFS) of 4 months. Similar results were confirmed in the STRATUS trial (MM‐010). In order to improve these results, the triplet oral combination Pomalidomide Cyclophosphamide and Dexamethasone (PCD) has been investigated. To the best of our knowledge, we still need “real life” data evaluating the efficacy and safety of the triplet PCD combination in relapsed MM patients.Aims:To evaluate efficacy and safety of PCD in unselected RRMM patients outside clinical trials.Methods:All consecutive patients treated in our institution between January 2015 to July 2018 were included in this retrospective institutional review board approved analysis if they fulfilled the following criteria: (i) diagnosis of multiple myeloma according to International Myeloma Working Group (IMWG) consensus criteria (ii) relapsed and/or refractory to at least two priors therapies, including lenalidomide and PI and (iii) treated with pomalidomide, cyclophosphamide and dexamethasone. Response to treatment was determined according to IMWG criteria. Progression‐free‐survival (PFS) and OS were estimated using the Kaplan‐Meier method.Results:49 consecutive patients were included. The median age was 66 years, including eight patients (16%) above 75 years. Nine (18%) patients had high‐risk cytogenetic (t(4;14) or 17p deletion). The median number of prior therapies was 3 (range, 2–8) and all patients were previously exposed to proteasome inhibitors and lenalidomide. Thirty‐nine (80%) patients were refractory to lenalidomide. Twenty‐eight (57%) patients were refractory to PI. A double refractory status (lenalidomide and PI) was identified in 21 (43%) patients. The ORR was 76%, including 27% very good partial response or better. With a median follow‐up of 16 months, the median PFS was 7.3 months and the median OS was not reached. Regarding safety, most frequent toxicity was hematologic, including 37% grade 3–4 cytopenias. Deep venous thrombosis were reported in 4% of patients. Nine patients (18%) discontinued therapy due to adverse event.Summary/Conclusion:This real‐life study demonstrated that PCD is therefore a manageable, cost‐effective and oral triplet combination for unselected RRMM patients eligible to Pd.
PF666 LOW JAK2 V617F ALLELE BURDEN PHI‐NEGATIVE CHRONIC MYELOPROLIFERATIVE NEOPLASMS MAY ASSOCIATE WITH ADDITIONAL CALR OR MPL MUTATIONS
Authors: Makarik T. , Odilov A. , Abdullaev A. , Nikulina E. , Treglazova S. , Stepanova E. , Soubortseva I. , Kovrigina A. , Melikyan A. , Sudarikov A. 
Published: June 2019

Background:Jak2 (Janus kinase 2) V617F, CALR (Calreticulin) exon 9 and MPL (receptor for thrombopoietin) exon 10 mutations are associated with the vast majority of Phi‐negative chronic myeloproliferative neoplasms (MPNs). These mutations affect sequential stages of prolipherative signal transduction and therefore after the emergence of one type of mutation another types basically should not have any selective advantages for clonal expansion. However simultaneous findings of these mutations have been reported by different investigators in up to 10% of MPN cases.Aims:To analyze cases with combined mutations in Russian cohort of MPN patientsMethods:Study includes 3267 samples, directed for genetic analysis to the National Research Center for Hematology between 2014 and 2019 from the patients with clinical evidence of MPN. DNAs and RNAs were extracted from blood using reagent kit from Interlabservice (Russia). Jak2 V617F mutation was quantitated by real‐time PCR kit from Syntol (Russia) according to manufacturers instructions. CALR exon 9 deletions/insertions were analyzed by fragment analysis (sensitivity > = 3%). MPL W515L/K mutations were assessed by in‐house allele specific PCR. All cases were tested for phi‐negativity using BCR‐ABl p210 PCR kit from Interlabservice (Russia).Results:In 406 of 3267 cases (12.5%) CALR mutations were detected. In 24 of these 406 cases (6%) Jak2 V617F mutation was found in addition to CALR mutation. Matched measures were obtained at least twice at different time points during the course of disease for these cases. In 19 from 24 (80%) cases with combined CALR and Jak2 mutations V617F allele burden was lower than 3%. Also combination of Jak2 V617F with MPL W515L/K was observed in 3 out of 3267 cases only. Two of them had V617F allele burden lower than 3% (Tabl.1).Summary/Conclusion:Additional mutations may coexist over low background of JAK2 V617F allele. Therefore cases of MPNs with low initial JAK2 V617F allele should be further tested for CALR (and possibly MPL) mutations to ensure correct disease and treatment monitoring. Further dynamic observation studies are required to assess the value of additional mutations for MPN disease progression and treatment outcome.image
PF685 THE RELATIONSHIP BETWEEN TOTAL ANTIOXIDANT CAPACITY AND JAK2V617F MUTATION IN ESSENTIAL THROMBOCYTHEMIA
Authors: Gaman M.‐A. , Moisa C. , Gaman A.M. 
Published: June 2019

Background:Essential thrombocythemia (ET) is a BCR‐ABL1‐negative myeloproliferative neoplasm associated in 50–60% of cases with the presence of the JAK2V617F mutation. Several studies have revealed that oxidative stress induces a growth advantage to JAK2V617F‐ positive clones, but little is known about the antioxidant status of ET patients.Essential thrombocythemia (ET) is a BCR‐ABL1‐negative myeloproliferative neoplasm associated in 50–60% of cases with the presence of the JAK2V617F mutation. Several studies have revealed that oxidative stress induces a growth advantage to JAK2V617F‐ positive clones, but little is known about the antioxidant status of ET patients.Aims:To evaluate the total antioxidant capacity (TAC) in patients with ET and to investigate if there are any differences between JAK2V617F‐positive cases and JAK2V617F‐negative ET cases in terms of TAC.Methods:We evaluated patients diagnosed with ET according to the WHO criteria (2016 revised) vs. healthy subjects (control group). Patients were classified based on age, sex and JAK2V617F mutational status. Haematological and biochemical parameters, as well as bone marrow aspirate or biopsy, were analyzed. Detection of JAK2V617F mutation was performed by RT‐PCR. TAC was measured using a multi‐detection microplate reader FLUOstar Omega (reagents from Sigma‐Aldrich). Data analysis was conducted using the student T‐test and a p‐value ≤ 0.05 was considered statistically significant. The study was approved by the Ethics Committee of the University of Medicine and Pharmacy of Craiova, Romania, approval no. 79/23.02.2017. All subjects agreed to partake in the study and signed a written informed consent.Results:The study group involved 58 ET patients (mean age 59.72 ± 14.63 years, age range 22–82): 25 males (40.32%, mean age 55.77 ± 15.80 years, age range 22–82) and 37 females (59.68%, mean age 62.14 ± 13.30 years, age range 23–81). 36 patients (62.07%) were JAK2V617F‐positive and 22 patients (37.93%) were JAK2V617F‐negative. 7 patients (12.07%) had homozygous genotype and 29 patients (50.00%) had a heterozygous genotype. TAC was decreased in patients with ET compared with healthy subjects and in JAK2V617F‐positive vs. JAK2V617F‐negative cases (p < 0.05). We found no significant differences between sexes in terms of age (men = 55.77 ± 15.80 years vs. women = 62.14 ± 13.30 years, p = 0.1116) or TAC (men = 0.50 ± 0.04 mM/L vs. women = 0.49 ± 0.06 mM/L, p = 0.3043). Also, we did not record significant differences in terms of TAC between JAK2V617F homozygous genotype vs. JAK2V617F heterozygous genotype (0.48 ± 0.05 mM/L vs. 0.49 ± 0.06 mM/L, p = 0.1686).Summary/Conclusion:In patients diagnosed with ET, TAC is decreased compared to normal individuals. Also, the decrease in TAC is more expressed in JAK2V617F‐positive cases vs. JAK2V617F‐negative cases or controls. No significant differences in terms of TAC were found between sexes or JAK2V617F homozygous vs. heterozygous genotype.
PF698 LUSUTROMBOPAG RELIABLY INCREASES PLATELETS REGARDLESS OF BASELINE PLATELET COUNTS IN THROMBOCYTOPENIC CHRONIC LIVER DISEASE PATIENTS UNDERGOING PLANNED INVASIVE PROCEDURES: RESULTS OF 2 PHASE 3 TRIALS
Authors: Brown R.S. , Imawari M. , Izumi N. , Osaki Y. , Bentley R. , Baykal T. , Ochiai T. , Kano T. 
Published: June 2019

Background:Lusutrombopag is an oral, small molecule thrombopoietin receptor agonist approved in Japan and US for improvement of thrombocytopenia, and in EU for severe thrombocytonia, associated with chronic liver disease in patients undergoing planned invasive procedures. The degree of thrombocytopenia may impact the treatment response to lusutrombopag and need for platelet transfusion.Aims:This analysis evaluates the increase in platelet count and maximum platelet count achieved according to baseline platelet count.Methods:L‐PLUS 1 and L‐PLUS 2 were two similar phase 3 multicenter, randomized, double‐blind, placebo‐controlled studies; L‐PLUS 1 (JapicCTI‐132323) was conducted in Japan and L–PLUS 2 (NCT02389621) was conducted globally. Patients with thrombocytopenia due to chronic liver disease received lusutrombopag 3 mg or placebo for up to 7 days prior to an invasive procedure scheduled 9–14 days after randomization. Patients were adults with platelet count (x109/L) <50 at baseline. Platelet transfusion was mandated if the platelet count remained <50 no more than two days prior to the planned invasive procedure. The change in platelet count over time was a key efficacy endpoint. A per‐protocol population from the two trials was integrated for this analysis; post‐platelet transfusion platelet counts were excluded from the analysis when calculating the proportion of patients who met a criterion and summary statistics for maximum platelet counts.Results:312 patients were randomized. Of the 270 patients in the per‐protocol population, 78.1% of patients in the lusutrombopag group (n = 137) achieved a platelet count ≥50 at least once during the study versus 30.1% of patients in the placebo group (n = 133). The platelet count increased by double or more in 47.4% and 3.8% in the lusutrombopag and placebo groups, respectively, and increased by 50% or more in 77.4% and 12.8%, respectively. The average maximum platelet count in the lusutrombopag group stratified according to baseline platelet count of <20, ≥20‐<30, ≥30‐<35, ≥35‐<40, and ≥40‐<50 was 56, 45, 64, 82, and 87, respectively (Figure). The average maximum change in platelet count in these strata were +41, 21, 32, 45, and 42, respectively.Summary/Conclusion:Patients on lusutrombopag experienced a clinically meaningful response in platelet count regardless of whether the baseline platelet count was above or below 35x109/L, thereby avoiding the need for use of platelet transfusion.image
PF732 AN INDEPENDENT OBSERVATIONAL STUDY OF REAL LIFE COSTS OF CARE TO MYELOMA PATIENTS IN THE ERA OF NOVEL THERAPIES
Authors: Thompson J. 
Published: June 2019

Background:Novel haematological therapies offer advantages in management of malignant and non‐malignant conditions, but treatment access is limited by cost, typically referenced as medication cost alone. The addition of real world costs of care provides a more complete cost‐benefit analysis, and limited published data and common perception have suggested additional costs are greater for novel agents.Aims:We analysed and compared total dollar value costs of care excluding the cost of the novel agent for myeloma patients treated first‐line with bortezomib and non‐novel agent based regimens in an inclusive (encompassing all patients within a local health network), real‐world cohort.Methods:We interrogated electronic and case note databases to record hospital admissions, outpatient visits, investigations, and non‐primary‐therapy medications and costed these using standard values using single payer government benchmarks. The primary end point was the real world cost of treatment per patient for the first year of treatment.Results:After using generalised linear models to adjust for patient age, gender, International Staging System (ISS) stage, trial status and transplant status, the mean yearly cost of care for patients receiving bortezomib‐based regimens was AU$24,162 (CI $20,207–28,118), which was 2.6% lower (CI −22.1–21.7, p = 0.814) than that for those receiving regimens not containing a novel agent ($26,300, CI $23,121–29,479) excluding the novel agent. Compared to patients at Stage 1 at baseline ($, CI$‐), costs of care were 62.2% higher (CI 50.1–81.8, p < .0001) for patients at Stage 3 at baseline ($, CI$‐). Costs were 36.0% lower (CI 18.2–49.9, p < .0001) for trial patients ($21,381, CI $17,404–25,358) compared to non‐trial patients ($25,130, CI $20,120–30,139). Yearly costs of care are estimated to be on average 51.5% higher (CI 22.0–88.1, p < .0001) for transplant patients ($27,288, CI $23,351–31,226) compared to non‐transplant patients ($17,088, CI $10,980–23,196).Summary/Conclusion:Contrary to common perceptions and previously published data, bortezomib‐based regimens do not confer higher costs of care in the real world than conventional regimens. Subgroup analysis indicates significant cost differences based on ISS stage, trial involvement, transplant status and age.
PF743 PENICILLIN PROPHYLAXIS AND PNEUMOCOCCAL VACCINE USE IN ADULT SICKLE CELL PATIENTS: A RETROSPECTIVE ANALYSIS OF CLINICAL PRACTICE AND OUTCOMES IN OXFORD, UK
Authors: Ejaz A. , Hayes S. , Akanni M. , Roy N. 
Published: June 2019

Background:Pneumococcal disease prophylaxis with antibiotics and vaccination has a clear mortality benefit in children with sickle cell disease (SCD), with the greatest benefit in children under 5 years [1]. The benefit in adults, who also have functional hyposplenia, is less clear with no trial evidence to support or refute prophylaxis in this group. Current guidelines [2] recommend that adults with SCD have pneumococcal vaccination every 5 years and take antibiotic prophylaxis only if they are compliant, so reducing the theoretical risks of antimicrobial resistance in those who are partially compliant.Aims:Our aim was to establish the current uptake of pneumococcal vaccination and antibiotic prophylaxis in our adult patients with SCD. We wished to ascertain whether a difference exists in episodes of infection for patients who are fully compliant with pneumococcal prophylaxis and those who are not. MiniTab 18 was used for data analysis.Methods:Adult patients with SCD known to the Oxford Red Cell tertiary centre were identified from annual review assessments and a descriptive analysis was undertaken on patient demographics, co‐morbidities, prophylaxis compliance and pneumococcal vaccination status, and episodes of infection occurring from 2015‐2019.Results:133 patients with SCD were identified. 53% were female and the median age was 34 years (range 16–75 years) (see Table 1). 67% of patients were prescribed antimicrobial pneumococcal prophylaxis. Of these, 21% were known to be non‐compliant. 100% of patients were asked to attend their GP for vaccination but only 58% of patients had documentation of pneumococcal vaccination. From 2015 to 2019 there were 41 episodes of infection recorded in 31 patients but only 12 had positive cultures. There was no significant difference in infection rate between patients on prophylaxis and compliant (17/31) and remaining patients (14/31) (p = 0.61). There was one episode of confirmed pneumococcal disease and this was in a patient non‐compliant with prophylaxis and not up‐to‐date with vaccination.Summary/Conclusion:While the majority of our patients were prescribed antibiotic prophylaxis, due to non‐compliance, only half of our cohort were taking antibiotics reliably. There were few culture positive cases of infection, indicating that adults with SCD are at lower risk of infection compared with children, consistent with the literature [3]. In our cohort, over the 3 year period, there was only 1 documented case of pneumococcal disease. The low incidence of infection may have been due to our cohort being of younger age, with few comorbidities and a relatively high proportion of lower risk genotype. This work highlights the need for prospective, randomised evidence in SCD patients to establish whether a benefit exists for pneumococcal prophylaxis in adulthood.image
PF753 IMPACT OF ANTI‐THYMOCYTE GLOBULIN DOSES IN UNRELATED HEMATOPOIETIC STEM CELL TRANSPLANTATION FOR PATIENTS WITH MYELOID NEOPLASM
Authors: Nam J.Y. , Bae S.H. , Kim M.K. , Hyun M.S. , Moon J.H. , Sohn S.K. 
Published: June 2019

Background:Anti‐thymocyte globulin (ATG) is widely used for the prophylaxis of graft‐versus‐host disease (GVHD) in hematopoietic stem cell transplantation (HSCT). However, there is still controversy regarding the optimal dose of ATG.Aims:We analyzed the impact of ATG doses in unrelated HSCT for patients with myeloid neoplasm.Methods:This was a retrospective multi‐center study that assessed the impact of ATG doses on clinical outcomes in patients with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) undergoing an unrelated HSCT. The patients who received peripheral blood stem cells (PBSC) transplantation after conditioning regimens containing i.v. busulfan (BU), fludarabine and rabbit ATG between 2010 and 2017 were included in this study.Results:A total of 96 patents, median age 45 years, with AML (n = 74) or MDS (n = 22) were included in our analyses. 66 patients (69%) received a myeloablative regimen (i.v. BU>6.4 mg/kg). High‐ATG (ATG 9 mg/kg), intermediate‐ATG (ATG 4.5–5 mg/kg) and low‐ATG (ATG 3 mg/kg) were given in 11, 49 and 36 patients, respectively. After a median follow‐up of 23 months, the cumulative incidence of extensive chronic GVHD was 9.1% in the high‐ATG group, 13.8% in the intermediate‐ATG group and 29.7% in the low‐ATG group (p = 0.31). The rate of 2‐year relapse‐free survival was significantly higher in the intermediate‐ATG group than other groups (30% in the high‐ATG group vs. 73.2% in the intermediate‐ATG group vs. 53.8% in the low‐ATG group, p = 0.048). The rate of 2‐year overall survival was similar (45.5%, 68.5% and 44.8%, respectively; p = 0.09). The rate of chronic GVHD–free and relapse‐free survival at 2 years was significantly higher in the intermediate‐ATG group (18.2% in the high‐ATG group vs. 53.8% in the intermediate‐ATG group vs. 18.8% in the low‐ATG group, p = 0.0086).Summary/Conclusion:Our study shows that the incidence of extensive chronic GVHD was similar regardless of the doses of ATG after transplantation of PBSC from unrelated donor for patients with AML or MDS. However, the rate of relapse‐free survival and the rate of a composite end point chronic GVHD–free and relapse‐free survival were significantly higher in the intermediate dose (4.5–5 mg/kg) of ATG group.