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Intravenous immunoglobulin (IVIg) is a common therapy for patients with immune thrombocytopenia (ITP). The initial response rate for IVIg is 80%[1][1] and is typically rapid, with some patients responding in 24 hours, although usually in 2–4 days.[2][2] When IVIg is used alone, the response is

Introduction Current treatment options for myelofibrosis (MF) are diverse; apart from rare patients who are eligible for allogeneic transplantation, active treatments are focused on controlling MF-related symptoms and are not disease modifying. Patients who are initially asymptomatic and those at low risk for progression are usually observed without active treatment (watch and wait) until the appearance of symptoms or progression. There are limited real-world data on the management of patients with MF in the United Kingdom (UK). The REALISM UK study documented the early management pathways for patients with MF in routine clinical practice. Method REALISM UK was a multi-centre, retrospective, non-interventional study in 15 UK secondary care centres. Eligible patients were those aged ≥18 years at diagnosis of MF, with diagnosis >6 months and ≤5 years prior to data collection and with ≥1 follow-up visit. Data on patient demographics, clinical characteristics, MF management strategies and outcomes were collected from patients' medical records; the observation period was from the date of MF diagnosis until data collection. The primary endpoint was the time from diagnosis to active treatment. Watch and wait strategies included supportive therapies (blood transfusions, erythropoiesis-stimulating agents, and steroids). Results A total of 200 patients were recruited (63% [n=126/200] with primary MF (PMF); 37% [n=74/200] with secondary MF). The median age at MF diagnosis was 69.7 years (interquartile range [IQR] 63.5-75.7) and 71% (n=141/200) had a JAK2 mutation. At diagnosis, 52% (n=104/200) of patients had International Prognostic Scoring System (IPSS) categories of intermediate-2 (Int-2) or high. Common documented features of disease at diagnosis included an enlarged spleen (47%, n=94/200), anaemia (44%, n=88/200), and constitutional symptoms (e.g. night sweats, unexplained fever, or weight loss [30%, n=60/200]). The median (IQR) time to first active treatment was 46 days (range 0-350) in the total population; patients with higher risk disease were prescribed active treatment sooner: IPSS low, 136.5 days (range 0-625; n=26); IPSS Int-1, 90 days (range 0-494; n=70); IPSS Int-2, 0 days (range 0-252; n=65); IPSS high: 0 days (0-216; n=39). The choice of first management strategy by IPSS at diagnosis is shown in Table 1. During the study period, watch and wait was the first management strategy for 54% (n=107/200) of patients, with the median (IQR) time from diagnosis to active treatment in this group being 322 (130-610) days. Constitutional symptoms were recorded in 20% (n=21/107) of patients for whom watch and wait was the first management strategy. Active treatment was started at diagnosis for 47% (n=93/200) of patients, with the most commonly used medications being hydroxycarbamide (22.5% [n=45/200]) and ruxolitinib (17.5% [n=35/200]). The median (IQR) treatment duration during the study observation window was 346 days (range 121-768) for hydroxycarbamide and 375 days (range 172-691) for ruxolitinib. In total, 5.5% (n=11/200) of patients were recorded as having undergone allogenic stem cell transplantation during the observation period. Conclusion Clinicians in the UK apply a broad range of management strategies for the treatment of patients with MF. Many patients were observed without active treatment following diagnosis, despite having symptomatic disease. The most common active treatments as first management strategies were hydroxycarbamide and ruxolitinib. Disclosures Mead: Pfizer: Consultancy; Novartis: Consultancy, Honoraria, Other: Travel/accommodation expenses, Research Funding, Speakers Bureau; Bristol Myers-Squibb: Consultancy. Somervaille:Novartis: Consultancy, Honoraria. Butt:Novartis: Consultancy, Honoraria, Speakers Bureau. Whiteway:Novartis: Consultancy, Honoraria, Speakers Bureau. Kirkpatrick:Novartis: Consultancy, Honoraria. Roughley:Novartis: Consultancy, Honoraria. Ewing:Novartis: Honoraria, Other: Meeting attendance sponsorship ; Bristol Myers-Squibb: Other: Meeting attendance sponsorship . Garg:Novartis: Consultancy, Honoraria. Harrison:Promedior: Honoraria; Shire: Speakers Bureau; Sierra Oncology: Honoraria; Celgene: Honoraria, Speakers Bureau; Roche: Honoraria; Novartis: Honoraria, Research Funding, Speakers Bureau; Incyte: Speakers Bureau; Gilead: Speakers Bureau; CTI: Speakers Bureau; AOP: Honoraria; Janssen: Speakers Bureau. Bains:Novartis: Employment. Chiu:Novartis: Employment. Hickey:OPEN VIE: Employment.

Background: Patients with lower-risk MDS (LR-MDS) are prone to iron toxicity due to long-term iron accumulation either caused by RBC transfusions or ineffective erythropoiesis. Nontransferrin bound iron (NTBI), including labile plasma iron (LPI), are toxic iron species that may mediate cellular damage via oxidative stress. The EUMDS registry collects prospective observational data on newly diagnosed LR-MDS patients from 145 centers in 17 countries since 2008. Methods: We analyzed serum from 247 LR-MDS patients collected at six-month intervals for ferritin, transferrin saturation (TSAT), hepcidin-25, soluble transferin receptor (sTfR) and toxic iron species (NTBI and LPI) in order to evaluate temporal changes in iron metabolism, the presence of potentially toxic forms of iron and their impact on survival, and quality of life. In addition, we measured the impact of iron chelation on the iron species levels and its impact on the outcome parameters. Results: The median age was 73 years (range: 37 to 95 years) and 66% were males. WHO2001 MDS-subtypes were RCMD (45%), RARS (22%), RA (18%), RAEB-1 (7%), 5q-syndrome (4%) and RCMD-RS (4%). The IPSS-R categories were: (very) low risk: 66%; intermediate risk: 11%; (very) high risk: 2% and unknown: 20%. The median EQ5D index score was 0.80 (p10 to p90: 0.52 to 1.00). The table shows iron parameters at registration, 1 and 2 years follow-up both in transfusion-dependent (TD) and transfusion-independent (TI) patients and according to: MDS-RS (RARS/RCMD-RS) or MDS Other (RA/RCMD/RAEB/5q-syndrome). Mean serum ferritin levels were increased in TD patients, compared to TI patients (Table). Increase of ferritin levels over time was high in both TD groups, but the increase was more pronounced in the RS subgroup. Elevated CRP levels (> 10mg/L) were observed in TD nonRS patients, especially during the first year after diagnosis. Markedly increased mean TSAT levels (>75%) occurred in the subgroup of TD-RS patients throughout the observation period. Hepcidin levels were most markedly elevated in TD nonRS patients at registration and remained elevated during follow-up (Table). Hepcidin levels were low in MDS-RS TI patients at all time points compared to nonRS MDS patients and decreased over time as a result of an increased (ineffective) erythropoiesis (Table). This is supported by the highest levels of STfR also noted in this patient category (data not shown). The highest NTBI and LPI levels were observed in TD-RS patients compared to the other 3 subgroups (Table). Both NTBI and LPI levels had a strong correlation (p 80%) occurred almost exclusively in patients with MDS-RS and/or previous transfusions. Both the EQ5D index score and EQ-VAS showed a negative correlation (r) with LPI levels with r = -0.09 (p = 0.028) and r = -0.07 (p=0.046) respectively. This negative effect of elevated LPI levels was most pronounced in the TD RS subgroup with a negative correlation of -0.17 for the EQ5D index score and -0.2 for the VAS score. In total 16 patients received iron chelation during the sample collection period (11 patients deferasirox, 4 patients desferioxamine and 1 patient unknown). LPI levels were normal in 14 out of the 17 samples collected during deferasirox treatment and in 2 out of 5 samples collected during desferoxamine treatment. The Kaplan-Meier curves (Figure) demonstrate the prognostic impact of elevated LPI levels by transfusion status as a time dependent variable; once a subject had an elevated LPI level, they remained in this group. Patients were censored at time of starting iron chelation (16 patients). In a multivariate analysis comparing elevated LPI levels and transfusion dependency to the control group with undetectable LPI and no transfusion showed a significantly decreased survival in all 3 risk groups after adjustment for age at diagnosis, baseline IPSS-R category and ESA treatment status; for details, see supplementary table. Conclusion: This study illustrates labile plasma iron species as a clinically relevant assay for identification of the toxic fraction of overt iron overload and its negative impact on HRQoL and overall survival in transfusion dependent and transfusion independent patients. Table. Table. Disclosures Culligan: Merck Sharp & Dohme (MSD): Honoraria; Abbvie: Other: Support to attend conferences; Takeda: Honoraria, Other: Support to attend conferences; Pfizer: Honoraria; Celgene: Other: Support to attend conferences; JAZZ: Honoraria; Daiichi-Sankyo: Other: Support to attend conferences. Garelius:novartis: Honoraria. de Witte:Celgene: Honoraria, Research Funding; Novartis: Research Funding; Amgen: Consultancy, Research Funding.

Improve stroke prevention in atrial fibrillation (AF) patients. AF patients on warfarin who visited Bradford Anticoagulation Clinic between January and December 2013 were listed randomly, then the first 200 patients were selected. Time in therapeutic range (TTR) over that year was calculated for each patient using the Rosendaal method. Exclusion criteria: 1. Patients recently started on warfarin (within 6 weeks). 2. Patients with a target international normalised ratio (INR) range other than 2.0–3.0. …

PB 2.54-1. Bauduer, F., Guichandut, J.P. & Ducout, L. (2004) Successful use of fresh frozen plasma and desmopressin for transurethral prostatectomy in a French Basque with combined factors V + VIII deficiency. Journal of Thrombosis and Haemosta

myeloma. The role of surgery in addition to radiotherapy for the management of MSCC continues to be debated [2,3]. The most persuasive evidence for the benefit of surgery in addition to radiotherapy for the management of MSCC came in 2005 from a randomised trial of 101 patients that showed improved functional outcomes and survival for MSCC managed by decompressive surgery followed by radiotherapy compared with radiotherapy alone [4]. However, this study was limited to highly selected patients recruited over 10 years and has been criticised on several methodological grounds [2]. Importantly in the context of myeloma, the trial excluded patients with haematological malignancies. Rades et al. [3] carried out a retrospective review of the outcome of 521 patients with less than three vertebral metastases with MSCC managed with radiotherapy alone. This series included 63 patients with myeloma/lymphoma (grouped together for analysis); 76% of the myeloma/ lymphoma patients experienced an improvement in motor function, 2% deteriorated and local control (defined as the absence of recurrence or progression of motor defects) was achievedin98%at1year.Onmultivariateanalysis,myeloma/ lymphoma was a highly significant factor predicting a favourable functional outcome. The authors highlighted myeloma/lymphoma patients as a group that should be managed with radiotherapy alone. These results are supported by a subsequent retrospective matched pair analysis of 324 patients with MSCC [2]; in this series the outcomes (motor function, ambulatory status, regaining ambulation, local control and survival) after radiotherapy alone were similar to those after surgery and radiotherapy. In the 48 patients in the series with myeloma/lymphoma, motor function improved in 63% and deteriorated in 2% of patients, with a high local control rate of 95% at 1 year of follow-up. The optimal radiotherapy dose fractionation schedule is uncertain in MSCC. In a retrospective multinational study of 172 myeloma patients with MSCC, a functional improvement after radiotherapy alone was observed in 52% of patients and 47% of non-ambulatory patients regained the ability to walk at 4 months [5]. A functional improvement was more common after long-course than short-course radiotherapy (76 versus 40% at 12 months, P¼0.003). The authors concluded that a schedule of 30 Gy in 10 fractions over 2 weeks was appropriate for myeloma MSCC. In summary, we believe that the current evidence does not support the use of surgical decompression in myeloma patients with MSCC; these patients are adequately managed with radiotherapy. Exceptions include patients with spinal instabilityand/orbonycompression(uncommoninmyeloma). Vertebroplasty and kyphoplasty remain useful options after radiotherapy if pain control has not been achieved.

A 60-year-old woman was admitted with dysarthria, unsteady gait and limb weakness. She had been diagnosed 5 years previously with symptomatic IgG k multiple myeloma and had been treated with ABCM [adriamycin, BCNU (carmustine), cyclophosphamide, melphalan], melphalan autograft, alphainterferon maintenance and a combination of cyclophosphamide with dexamethasone for relapsed disease. At this presentation she was transfusion-dependent despite erythropoietin/granulocyte colony-stimulating factor support and her general health was deteriorating. On examination she had dysarthria and an ataxic gait. Investigations showed a stable IgG paraprotein of 22 g/l. Preand post-contrast head computed tomography was normal. A magnetic resonance imaging scan of her head demonstrated marked meningeal enhancement, particularly in the posterior fossa, consistent with leptomeningitis (left image, post gadolinium contrast). A lumbar puncture was performed and showed a low glucose (0AE5 mmol/l), a high protein (2AE3 g/l) and a high white cell count. The cerebrospinal fluid cytology showed a large number of plasma cells, all with a neoplastic phenotype CD19–56+/) (right image). Treatment options were discussed and she was treated palliatively with dexamethasone and died peacefully 12 d after this presentation.