BACKGROUND:Transient positivity for hepatitis B core antibody (Anti-HBc) following intravenous immunoglobulin (IVIG) and subcutaneous immunoglobulin exposure is a well-described phenomenon. The aim of this study was to retrospectively review Hepatitis B viral screening practices in IVIG recipients in a hematology specific cohort at a single center. METHODS:Electronic databases were analyzed to identify all hematology patients who received IVIG from September 2022 to March 2022 at a single Irish center (n = 43). The proportion of patients that had a baseline anti-HBc tested prior to IVIG receipt was assessed as well as the proportion of patients that developed a transiently positive anti-HBc following IVIG exposure. Data were also collected relating to signal cut-off ratios in patients with detectable anti-HBc post-IVIG. RESULTS:58.1% of patients had at least one serological hepatitis B viral test sent prior to IVIG exposure. Anti-HBc was the least common serological investigation performed prior to IVIG exposure (21% of recipients). A positive or equivocal "low level antibody" was identified in 15% of recipients and this was proven to be transient in all cases. CONCLUSION:The minority of hematology patients had a baseline anti-HBc assessed prior to IVIG exposure. All patients in this study had the potential to require further immunosuppressive therapies, which could be limited by a misleading anti-HBc result. We therefore advocate for baseline anti-HBc testing to be performed prior to IVIG exposure in hematology patients and for cautious interpretation of anti-HBc results taking into account signal cut-off ratios post-IVIG exposure.

A 64- year- old man presented with a 3- month history of mild constitutional symptoms. Computed tomography of the abdomen and pelvis showed intra- abdominal lymph-adenopathy and splenomegaly, suggestive of haematological malignancy. A full blood count was normal. Serum protein electrophoresis showed a slightly elevated IgM level (7.24 g/l) and a monoclonal IgM band too weak to quantify. Bone marrow and lymph node biopsy were consistent with an indolent small B- cell lymphoma, most likely a marginal zone lymphoma. As there was no indication for immediate treatment, a watch and wait approach was undertaken. Four months later, the patient developed profuse watery diarrhoea and weight loss. This was associated with hypoalbuminaemia (albumin 22 g/l). Colonoscopy showed non- specific colitis that did not respond to a trial of systemic corticosteroids. Magnetic res-onance enterography was performed, which demonstrated diffuse mucosal thickening throughout the small bowel (top left). Oesophago- gastro- duodenoscopy showed extensive ab-normality within the mucosa of the duodenum (top right). Histological assessment of the duodenal mucosa showed ex-pansion of the lamina propria by eosinophilic material within the lymphatics and in the interstitium (bottom left, haema-toxylin and eosin). This material was negative on amyloid staining and positive by periodic acid Schiff staining (bottom right). Immunohistochemistry showed IgM deposition with kappa light chain restriction. Repeat electrophoresis showed that the IgM level had increased to 39 g/l with a paraprotein of 15 g/l.

Abstract Background Bone-protective treatment should always be considered when commencing glucocorticoid therapy in individuals at high risk of fracture, as outlined in recent guidelines (National Osteoporosis Guideline Group, July 2018). Despite this, many patients receive high dose glucocorticoids (>7.5mg/kg/day or equivalent for >3 months) during treatment of haematological malignancy without formal assessment of bone health. Methods Twenty-five patients with Non-Hodgkin’s Lymphoma (NHL) on high dose steroid chemotherapy protocols were retrospectively assessed. The inclusion criterion was defined as any patient commenced on a cyclophosphamide, doxorubicin, vincristine and prednisolone (CHOP) containing protocol from 1/8/2020 to 1/8/21. Data was collected from electronic and written patient records. Information regarding patient age, diagnosis, steroid preparation and dose, presence of risk factors for osteoporosis and calcium and vitamin D prescriptions were collected. Radiological imaging was reviewed to assess for the occurrence of fragility fractures. Each patient had a FRAX® score calculated to assess fracture risk. Results The mean age of patients studied was 67 years and equally distributed between males and females. All patients had NHL. 32% (n=25) of patients were identified to be at high risk for fracture (FRAX® score >20% ten-year probability of major osteoporotic fracture). 16% had already established fragility fractures prior to commencing steroid treatment. 28% of patients were females over the age of 70 years. Only 12% of patients received vitamin D and calcium supplementation. No patient commenced bone protection therapy. Conclusion Omission of bone health assessment prior to high dose glucocorticoid treatment is prevalent in haematological malignancy and places patients at risk of significant morbidity. Patients are not routinely considered for protective measures including calcium and vitamin D supplementation and bone protection therapy. A simple risk-assessment tool and education to staff and patients prior to glucocorticoid therapy could significantly improve practice in this area. It is now planned to introduce routine risk assessment for this cohort of patients, with re-audit following implementation.

The British Journal of Haematology publishes original research papers in clinical, laboratory and experimental haematology. The Journal also features annotations, reviews, short reports, images in haematology and Letters to the Editor.

An 18-year-old female with no prior medical history, presented with a three-week history of nausea, dyspnoea on minimal exertion and palpitations. On examination, sinus tachycardia of up to 120 beats per minute at rest was noted. Echocardiogram and computed tomography (CT) pulmonary angiogram revealed a large pericardial effusion (left). CT thorax and positron emission tomography (PET) scan showed a 21 × 60 mm superior and anterior mediastinal mass (standardised uptake value, SUV 4·5) with anterior pericardial uptake, surrounding the aortic arch and great vessels and causing near occlusion of the right pulmonary artery. Full blood count and blood film were normal. Analysis of pericardial fluid (right) showed a population of immature myeloid cells, some containing cytoplasmic granules and Auer rods, indicating infiltration of the pericardium by myeloblasts. Biopsy of the mass showed dense sclerosis and a diffuse infiltrate of intermediate size myeloblasts with irregular nuclei and pale cytoplasm. Immunohistochemistry was suboptimal due to sclerosis but demonstrated that the neoplastic cells expressed CD45, CD117, CD34, CD68 and BCL2 with a high MIB1 index (>70%). There was no expression of CD2, CD3, CD4, CD5, CD8, CD20, PAX5, terminal deoxynucleotidyl transferase, myeloperoxidase (MPO), CD30, CD23 or CD56. CD79a was equivocal. Overall, this was indicative of myeloid sarcoma (MS), though the degree of sclerosis was unusual. Cells in the pericardial fluid expressed CD45, CD34 and CD117 with some expression of MPO and with Sudan black B positivity, confirming the presence of myeloblasts. Fluorescence in situ hybridisation analysis of pericardial fluid showed monosomy 7. Analysis for NPM1 and FLT3 mutations was negative. There was no evidence of bone marrow involvement on bone marrow aspiration or trephine biopsy. The patient was treated with induction/consolidation chemotherapy, with PET then showing a complete metabolic response; monosomy 7 was no longer detectable in pericardial fluid. The patient was then successfully consolidated with a matched unrelated donor allogeneic stem-cell transplant. She remains in remission 10 months post-transplant. MS is a rare myeloid neoplasm, defined as a tumour mass of leukaemic cells that occurs in extramedullary tissues at almost any site, in isolation or associated with acute myeloid leukaemia or other myeloid neoplasm. Virtually all patients develop overt bone marrow involvement if untreated. Malignant effusions in haematological malignancies are rare in comparison with solid tumours. A small number of case reports describe MS of the pericardium, with some reports of simultaneous serosal effusions at other sites. Serosal fluid can offer high-yield information in diagnostically challenging cases. It is important to consider MS in the differential diagnosis of a mediastinal mass with pericardial or pleural effusions.

Over the last twenty years, chronic myeloid leukemia (CML) has come to be considered a paradigm for rationally selected, targeted inhibition of the disease-specific, BCR-ABL1 tyrosine kinase activity. However, a minor but significant numbers of patients either fail, or have suboptimal responses to first line tyrosine kinase inhibitor (TKI) therapy. The causes of a suboptimal response are many, with the acquisition of ABL1 kinase domain mutations (KDMs) contributing to resistance being widely studied. These ABL1 KDMs usually become apparent within the first two years of starting TKI therapy and their discovery has led to the development of second and third generation TKIs [1]. ABL1 KDMs have been detected throughout the kinase domain with ten common mutations accounting for the majority of those observed [2]. However, rare and novel mutations continue to be detected in TKI-resistant patients with reporting of such cases necessary for future understanding of real-world CML patient management [3]. A 44 year-old man presented with fatigue, weight loss, night sweats, abdominal discomfort, and a hemoglobin of 9.9 g/dl, white cell count of 353.9•109/l and platelet count of 130•109/l. The patient had a marked splenomegaly detected 17 cm below the costal margin. Bone marrow aspirate showed hypercellularity, myeloid metaplasia, only 1% basophils and no myeloblasts with cytogenetics detecting the t(9;22) translocation in all metaphases analysed. Quantitative reverse-transcription polymerase chain reaction detected e13a2 BCR-ABL1 transcripts at a high level, all consistent with a diagnosis of high-risk (Sokal score 1.5; EUTOS score 88), chronic phase CML. The patient commenced nilotinib 300 mg twice daily with BCR-ABL1 transcript levels decreasing very slowly (Figure). Within the first year of treatment he experienced intermittent eye irritation, conjunctival hyperemia which required occasional steroid eye drops and ocular lubricant, and a persistent sensation of asthenia with regular myalgias. His peripheral blood BCR-ABL1 transcript level (Internationally Standardised) at twelve months was a suboptimal 4.87% prompting switch to dasa­tinib 100 mg once daily increased to 140 mg once daily. At twenty months post-diagnosis, the BCR-ABL1 transcript level was 2.12% triggering analysis for an ABL1 KDM as previously described [4] and of which no mutation was detected (Figure). Despite a continued slow decline in BCR-ABL1 transcripts, a major molecular response was never achieved with re-analysis for an ABL1 KDM at 47 months detecting an ABL1 T240A mutation (c.718A>G, p.Thr240Ala; reference sequence NM_005157.5). The patient is currently well with persistent thrombocytopenia secondary to dasatinib and occasional myalgias. He continues attending for regular close molecular monitoring with a most recent BCR-ABL1 level of 0.15% five years post diagnosis. Figure. BCR-ABL1 transcript levels throughout disease course To date, real-world evidence of the degree of TKI resistance conferred by acquisition of the ABL1 KDM T240A has been unclear: this mutation has been previously described once in highly selected CML stem cells cultured in vitro and once at a low level in a CML patient with multiple other mutations during second line dasatinib therapy [5, 6]. The case reported herein provides evidence for acquisition of the T240A mutation to contribute to a sub-optimal molecular response in a patient with chronic phase CML. Whether the T240A mutation was present at a level below the detection sensitivity of Sanger sequencing at 20 months is not known. The introduction of next-generation, deep-sequencing approaches are likely to improve ABL1 KDM detection allowing a timelier re-consideration of TKI therapy [7].

Objectives:To develop a pharmacokinetic model describing total and unbound teicoplanin concentrations in patients with haematological malignancy and to perform Monte Carlo simulations to evaluate target attainment of unbound trough concentrations with various dose regimens.Methods:This was a hospital-based clinical trial (EudraCT 2013-004535-72). The dosing regimen was 600/800 mg q12h for three doses then 600/800 mg daily. Serial total and unbound teicoplanin concentrations were collected. Maximum protein binding was estimated from serum albumin concentration. Population pharmacokinetic analyses and Monte Carlo simulations were conducted using Pmetrics®. Target total and unbound trough concentrations were ≥20 and ≥1.5 mg/L, respectively.Results:Thirty adult patients were recruited with a mean (SD) bodyweight of 69.1 (15.8) kg, a mean (SD) CLCR of 72 (41) mL/min and a median (IQR) serum albumin concentration of 29 (4) g/L. A three-compartment complex binding pharmacokinetic model best described the concentration-time data. Total and unbound teicoplanin concentrations were related by serum albumin concentration and a dissociation constant. CLCR and bodyweight were supported as covariates for CL and volume of the central compartment, respectively. Dosing simulations showed that high CLCR was associated with reduced probability of achieving target total and unbound trough concentrations. Low serum albumin concentration was associated with a reduced probability of attaining target total but not unbound trough concentrations. A method to estimate the unbound teicoplanin concentration from the measured total concentration at different serum albumin concentration was demonstrated.Conclusions:Standard teicoplanin dosing regimens should be used with caution in patients with haematological malignancy. Bodyweight, CLCR and serum albumin concentration are important considerations for appropriate dosing.

Abstract Introduction Myelodysplastic Syndrome (MDS) is classically a disease of older people, with median age at presentation of 70-75 years. The incidence of MDS is estimated at 5-13/100,000/year, but rises to >20/100,000/year in older populations. An increase in diagnosis over the last decades is in part due to improved recognition of MDS, but likely also to an increase in the ageing population. There is very little data on the clinical course, management and outcomes for very old patients (≥85 years of age) with MDS. Patients and Methods: This was a retrospective, multicentre analysis of 84 patients with MDS or Chronic Myelomonocytic Leukemia (CMML) aged ≥85 years at diagnosis from 6 centres in Ireland. Results: We identified 84 patients aged ≥85 years at time of diagnosis of MDS (n= 70) or CMML (n=14), including 47 men (56%) and 37 women (44%). Median age at diagnosis was 87 years (range 85-98). Most patients (93%) were anemic at presentation, including 45/47 men (96%) and 33/37 women (89%). Median hemoglobin (Hb) was 9.5 g/dl (range 5.9 -13.8). Median neutrophil count was 2.4 x109/L (range 0-72). Forty-four patients had thrombocytopenia (median platelet count 144 x 109/L (range 18-624)). Data regarding co-morbidities were available for 75 patients: 69% had hypertension, 36% ischemic heart disease, 39% atrial fibrillation, 31% heart failure, 19% diabetes and 39% renal dysfunction. Ferritin was elevated in 18 (32%) of 57 patients tested. 2006 WHO subgroups were reported for 81 patients: RCMD (32; 40%), CMML (14; 17%), RA (10; 12%), RAEB-1 (10; 12%), RAEB-2 (7; 9%), RARS (2; 3%), t-MDS (2; 3%), Hypoplastic MDS (1; 1%) and 5q- Syndrome (1; 1%). Cytogenetic analysis was performed in 49 patients (58%); results were available for 39 (46%). No patient had molecular studies for MDS-associated mutations or p53 deletions/mutations. Karyotype was normal in 23 patients (59% of those with results available), deletion Y in 5 (13%), Trisomy 8 in 5 (13%), complex in 3 (7.7%), 5q- in 2 (5.2%), and monosomy 7 in 1 (2.5%). Risk stratification by IPSS-R was available for only 37/84 patients, primarily due to lack of cytogenetic testing. Data were available regarding treatment strategies for 81 patients. Thirty-five (43%) received supportive care only. Forty-five patients (57%) were transfused; 29 (34%) became transfusion-dependent during the course of their disease. Of these, only 14 (48%) received erythropoietin (EPO). Of 50 patients with significant anemia likely to cause symptoms (Hb < 10g/dl), only 21 (42%) received EPO. Five patients (6%) received azacitidine (1-18 cycles; median 5), 7 (8%) received G-CSF; none received lenalidomide or iron chelation. Median survival for all patients was 17 months (range 0-147), 16 months for men (range 0-70), and 27 months for women (range 1-147). In 35 patients who had IPSS-R data available, median survival was 49 months for Very Good, 30 months for Good and 13 months for Intermediate category patients. For 4 patients in the Poor and Very Poor categories median survival was 1, 5, 7 and 28 months. Median survival for patients with RA was 28 months (n=10), RCMD 25 months (n=29), CMML 13 months (n= 14), RAEB-1 10 months (n=10) and RAEB-2 19 months (n=7). Six patients (including 3 with RAEB-1, 1 with CMML and 1 with t-MDS) developed Acute Myeloid Leukaemia (7%) at a median of 4.5 months from diagnosis. Median survival for these patients was 9.5 months. Of 84 patients, 60 have died. The main causes of death included marrow failure, sepsis, cardiac events, other malignancies and gastrointestinal bleeding. Conclusions Anemia is the commonest presenting feature of MDS in the very old, and may be the sole cytopenia. Unexplained anemia in the very old should trigger suspicion of underlying MDS, especially if associated with a high MCV. In many patients over 85 years cytogenetic analysis is not performed, precluding accurate prognostic evaluation. MDS in these very old patients is not often actively managed with pharmacological intervention or chemotherapy. Up to 50% of transfusion-dependent patients do not receive erythropoeitin. Azacitidine and lenalidomide are infrequently used. Co-morbidities (especially cardiac and renal disorders) are very common. Survival can be prolonged, especially in patients with low-risk disease. With an ageing population, management of very elderly patients with MDS is becoming more challenging and a more proactive approach should be considered. Figure. Figure. Disclosures Quinn: Janssen: Honoraria.

Introduction Data are limited on the optimal management of cryptogenic TIA/stroke patients with a patent foramen ovale (PFO)±inter-atrial septal aneurysm (IASA), especially with an inherited thrombophilia. Methods Prospectively-collected data on TIA/ischaemic stroke patients with PFO, IASA or both who received ‘goal-directed secondary-prevention medical treatment' were analysed. All patients had trans-oesophageal echocardiography, anti-nuclear, anti-cardiolipin, anti-beta 2 glycoprotein I antibodies, rheumatoid factor, lupus anticoagulant, protein C&S, anti-thrombin, factor VIII activity, activated protein C resistance, Factor V Leiden, prothrombin gene and MTHFR-c.677C>T mutation screening. ENA and homocysteine were assessed in the latter study period. Results Eighty-three patients were recruited. Mean follow-up: 48.1months. Forty-seven patients (56.6%) had an isolated PFO, 32 (38.6%) a PFO and an IASA, and 4 (4.8%) an IASA alone. Eighteen (21.7%) had ≥1 abnormality on thrombophilia screening. The most important abnormalities which lead to treatment changes in 11 patients (13.3%) were primary anti-phospholipid syndrome (N=3; 3.6%), protein S deficiency (N=2; 2.4%) hyper-homocysteinaemia (N=6/72 screened, 8.3%). Four patients (4.8%) opted for PFO closure: two with protein S deficiency, and two with no identified thrombophilia. Seven (8.4%) had recurrent TIA/ischaemic stroke during follow-up (overall annualised incidence: 2.1%), of whom five had a PFO alone and two a PFO and IASA. Discussion Comprehensive arterial and venous thrombophilia screening is warranted in TIA/ischaemic stroke patients with a PFO±IASA, is conclusively abnormal in over a fifth, and informed important decision-making regarding individualised therapy in 13.3% of patients. The incidence of recurrent vascular events in this population is low on optimal, personalised secondary-prevention treatment, even with an underlying thrombophilia.

OBJECTIVES:To demonstrate the incidence, characteristics, treatment and outcomes of patients with therapy-related myelodysplastic syndromes and therapy-related acute myeloid leukaemia (t-MDS/AML) in a tertiary referral centre.METHODS:Patients meeting the diagnostic criteria for t-MDS/AML from 2003 to 2014 were reviewed to analyse their diagnostic features, details of antecedent disorder and treatment, approach to management and survival.RESULTS:39 patients who developed t-MDS/AML were identified with incidence of 8.7%. Median age and gender distribution were similar to de novo MDS but t-MDS/AML patients had greater degree of cytopenia and adverse karyotypes. Time to development of t-MDS/AML was shortest for patients with antecedent haematological malignancy compared to solid tumours and autoimmune disorders (46, 85 and 109 months). Patients with prior acute leukaemia had the shortest latency and poor overall survival. Treatment options included best supportive care (56%), Azacitidine (31%) or intensive chemotherapy/allogeneic transplant (13%). Median OS of all patients was 14 months. Survival declined markedly after two years and 5-year OS was 13.8%. Longer survival was associated with blast count <5% at diagnosis, previous haematological disorder, lower risk IPSS-R and a normal karyotype. Four out of five patients who received intensive therapy/transplant remain alive with median OS of 14 months. Median OS of Azacitidine-treated group was 11 months.DISCUSSION:t-MDS/AML patients showed unique characteristics which influenced their treatment and outcomes. IPSS-R may be useful in risk-adapted treatment approaches and can predict outcomes. Survival remains poor but improved outcomes were seen with allogeneic transplantation. Azacitidine may be effective in patients unfit for intensive therapies.

ABSTRACT The objective of this study was to explore the following aspects of teicoplanin use in patients with hematological malignancy: early attainment of target trough concentrations with current high-dose teicoplanin regimens, variability in unbound teicoplanin fractions, factors associated with observed total and unbound trough concentrations, efficacy and toxicity, and renal function estimation. This was a single-center, prospective study. Samples for determination of trough concentrations were taken on days 3, 4, 7, and 10. Total and unbound teicoplanin concentrations were determined using validated high-performance liquid chromatography methods. Regression analyses were used to identify the factors associated with the trough concentration. Thirty teicoplanin-treated adults with hematological malignancy were recruited. Despite the use of dosages higher than the conventional dosages, the proportions of patients with a trough concentration of ≥20 mg/liter at 48 h and at 72 h were 16.7% and 37.9%, respectively. Renal function was significantly negatively associated with total trough concentrations at 48 h and 72 h (P < 0.05). For an average hematological malignancy patient (creatinine clearance = 70 ml/min), sequential loading doses of at least 12 mg/kg of body weight may be needed to achieve early adequate exposure. In the absence of measured creatinine clearance, estimates obtained using the Cockcroft-Gault (total body weight) equation could prove to be an acceptable surrogate. The unbound fractions of teicoplanin were highly variable (3.4 to 18.8%). Higher unbound fractions were observed in patients with low serum albumin concentrations. Teicoplanin was well tolerated. Teicoplanin loading doses higher than those in current use appear to be necessary. Increased dosing is needed in patients with increased renal function. The high variability in protein binding supports the contention for therapeutic drug monitoring of unbound teicoplanin concentrations. (This study has been registered with EudraCT under registration no. 2013-004535-72.)

Objectives: To describe the population pharmacokinetics of teicoplanin in adult patients with haematological malignancies receiving higher than standard doses, and to perform Monte Carlo simulations to determine dosing regimens associated with optimal teicoplanin concentrations.Methods: This was a hospital-based clinical trial (EudraCT 2013-004535-72). Nine blood samples were collected on Day 3, plus single trough samples on Days 7 and 10, and 24 and 48 hours after the last dose. Teicoplanin minimum inhibitory concentrations were determined for Gram-positive isolates from study patients. Population pharmacokinetic analyses and Monte Carlo dosing simulations were undertaken using Pmetrics.Results: Thirty adult haematological malignancy patients were recruited with a mean (SD) loading dose, age, total body weight, and creatinine clearance of 9.5 (1.9) mg/kg, 63 (12) years, 69.1 (15.8) kg, and 72 (41) mL/min, respectively. A three-compartment linear pharmacokinetic model best described the teicoplanin concentration data. Covariates supported for inclusion in the final model were creatinine clearance for clearance and total body weight for volume of the central compartment. The median (IQR) area under the concentration-time curve from 48 to 72 hours (AUC(48-72h)) was 679 (319) mg.h/L. There was a strong correlation between the AUC(48-72h) and trough concentration at 72 hours (Pearson correlation coefficient 0.957, p < 0.001). Dosing simulations showed that administration of five loading doses at 12-hourly intervals, stratified by total body weight and creatinine clearance, increased the probability of achieving target concentrations within 72 hours.Conclusions: To increase the number of patients achieving optimal teicoplanin concentrations an individualized dosing approach, based on body weight and creatinine clearance, is recommended. (C) 2017 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Abstract Background: The presence of significant marrow fibrosis has previously been shown to be a poor prognostic factor in patients with myelodysplastic syndrome (MDS). Associations between fibrosis and higher transfusion requirements, multilineage dysplasia, and an increased rate of leukaemic transformation have been demonstrated. Currently, the presence of fibrosis is not included in standard risk scores for MDS such as the Revised International Prognostic Scoring System (IPSS-R) nor is fibrosis included in the current WHO classification for MDS. It is also not certain whether the presence of fibrosis should alter current treatment algorithms for patients. More information is needed to further assess both the prognostic and therapeutic implications of the presence of significant fibrosis in this patient population. Methods: We conducted a retrospective study utilizing a database of 247 patients with diagnosed MDS in a single center from 2000-2014. Bone marrow trephine samples for 200 of these patients were assessed using the European consensus on grading bone marrow fibrosis. Data was collected on: age, gender, WHO classification, marrow blast percentage, cytogenetics, progression to AML, treatment with azacitadine, and overall survival. These characteristics were compared between patients without significant fibrosis (grade 0/1) and those with significant fibrosis (grade 2/3). Our aim was to identify potential significant associations with MDS fibrosis and to assess whether treatment with azacitadine influenced these parameters or overall survival between the two groups. Results: Of 200 patients, 38 were found to have significant fibrosis (19%) versus 162 without significant fibrosis (81%). There was no significant difference in age or gender between the two groups. The commonest WHO category in both groups was RCMD (31.58% v 48.77%) in the fibrosis and non-fibrosis groups respectively. IPSS-R score was determined for 152 patients where data was available. There was no significant difference observed in IPSS-R Score between the two groups. Cytogenetic data was available on 175 patients. The commonest cytogenetic result in both groups was normal karyotype (55.3% v 52.5%). In the fibrosis group this was followed by complex cytogenetics (> 2 abnormalities) (23.68%) and trisomy 8 (7.89%). The presence of a cytogenetic abnormality was not significantly different in those with or without fibrosis (p=0.69). A significant difference was found between patients' marrow blast percentage at diagnosis (average 5.4% blasts in fibrotic patients versus 3.6% in non-fibrotic patients (p=0.04)). There were no differences in diagnostic haemoglobin level, neutrophil count, and platelet count. Acute Myeloid Leukaemia (AML) developed in 31 patients. The presence of fibrosis was associated with an increased rate of AML transformation with 27% compared with 13.5% in patients without fibrosis (p=0.05). Median overall survival was decreased in the fibrosis group compared to the non-fibrosis group (29 months versus 42 months, p=0.02). A total of 36 patients (25 of whom progressed to AML) received azacitadine treatment (9 (24%) patients with fibrosis and 27 (17%) patients without fibrosis). Patients with fibrosis had a longer median survival than those without (29 months and 19 months respectively) but this difference was not statistically significant (p=0.48). Conclusion: Marrow fibrosis adversely affects overall survival in patients with MDS. Patients with fibrosis are more likely to present with higher marrow blast counts and to progress to AML. Patients with fibrosis who received azacitadine appeared to have an overall higher survival than those without fibrosis. However, the numbers of patients who received azacitadine were small. This study confirms the adverse prognostic influence of marrow fibrosis in patients with MDS, but the presence of fibrosis may not adversely affect the responsiveness to azacitadine therapy. Table IPSS-R Score - Fibrosis versus Non-Fibrosis Table. IPSS-R Score - Fibrosis versus Non-Fibrosis Figure Overall Survival (Non-Fibrosis versus Fibrosis) Figure. Overall Survival (Non-Fibrosis versus Fibrosis) Disclosures Desmond: Novartis: Honoraria.

Sequence-specific RNA binding proteins (RBP) are important regulators of the immune response. RBP modulate gene expression by regulating splicing, polyadenylation, localization, translation and decay of target mRNAs. Increasing evidence suggests that RBP play critical roles in the development, activation and function of lymphocyte populations in the immune system. This review will discuss the post-transcriptional regulation of gene expression by RBP during lymphocyte development, with particular focus on the Tristetraprolin family of RBP.