Jonathan Lambert

The JAK2V617F mutation and thrombosis

Since the discovery of the JAK2V617F mutation, the clinical and pathological consequences of this acquired defect have been extensively investigated to determine whether its presence characterises a distinct subgroup of myeloproliferative disorders (MPD). MPD management remains highly dependent on the patient’s thrombotic risk. Whether the presence of the JAK2V617F mutation modifies the thrombotic risk is currently contentious, although there is increasing clinical evidence to suggest that the mutation may be variably associated with thrombosis. These observations are further supported by laboratory parameters which suggest that the JAK2V617F mutation may confer increased activation of leucocytes and platelets in MPD. The role of screening for the JAK2V617F mutation in patients presenting with thrombosis without overt MPD is unclear, but appears justified in cases of idiopathic splanchnic vein thrombosis.

Prognostic role of PET scanning before and after reduced-intensity allogeneic stem cell transplantation for lymphoma.

Allogeneic stem cell transplantation (SCT) is an established therapy for patients with relapsed lymphoma, but the role of positron emission tomography (PET) scanning preallogeneic and postallogeneic SCT is uncertain. We investigated whether pretransplantation PET status predicted outcome after allogeneic SCT and whether PET surveillance after transplantation provided additional information compared with computed tomography (CT) scanning. Eighty consecutive patients with lymphoma who received a reduced-intensity allogeneic SCT were entered onto a prospective trial. PET and CT scans were performed before transplantation and up to 36 months after transplantation. Forty-two patients were PET-positive before transplantation. Pretransplantation PET status had no significant impact on either relapse rate or overall survival. Thirty-four relapses were observed, of which 17 were PET-positive with a normal CT scan at relapse. Donor lymphocyte infusion (DLI) was administered in 26 episodes of relapse and was guided by PET alone in 14 patients. These findings suggest that, in contrast to autologous SCT, pretransplantation PET status is not predictive of relapse and survival after allogeneic SCT for lymphoma. Posttransplantation surveillance by PET detected relapse before CT in half of episodes, often allowing earlier administration of DLI in patients with recurrent lymphoma, and permitted withholding of potentially harmful DLI in those with PET-negative masses on CT scans.

Elevated serum microRNA 483-5p levels may predict patients at risk of post-operative atrial fibrillation

OBJECTIVES Post-operative atrial fibrillation (POAF) is the commonest post-operative cardiac arrhythmia, affecting ∼1 in 3 patients undergoing coronary artery bypass grafting (CABG). Although its aetiology is complex, atrial substrate changes may pre-dispose to its onset. This study aims to ascertain the atrial microRNA signature of POAF and determine the potential for circulating microRNA as a pre-operative biomarker for this arrhythmia. METHODS Thirty-four patients undergoing non-emergent, on-pump CABG were prospectively recruited. Right atrial biopsies were taken intra-operatively and snap frozen for RNA extraction. Plasma was obtained at 24 h pre-operatively and at 2 and 4 days post-operatively. POAF was defined by continuous Holter recording. Inter-group comparisons were performed using Students t-test or analysis of variance as required. Receiver operating characteristic (ROC) analysis was used to determine the diagnostic accuracy of pre-operative serum miRNA as a POAF biomarker. RESULTS Sixteen microRNAs were differentially expressed in the atrial myocardium of POAF patients when compared with those maintaining sinus rhythm. miR-208a was the most underexpressed [fold change (FC) = 2.458] and miR-483-5p the most overexpressed (FC = 1.804). miR-483-5p also demonstrated significant overexpression in the pre-operative serum of these patients, with ROC analysis demonstrating an overall predictive accuracy of 78%. CONCLUSIONS This study provides the first description of atrial myocardial and circulating plasma microRNA in POAF patients. Our findings suggest POAF may be associated with pre-existing atrial substrate differences predisposing to arrhythmogenesis. Moreover, this study highlights the potential for miR-483-5p in biomarker development. Further work must now perform prospective, targeted validation of these results in a larger patient cohort.

Comparison of PET/MRI With PET/CT in the Evaluation of Disease Status in Lymphoma

Purpose The primary aim was to compare the diagnostic performance of PET/MRI (performed with basic anatomical MRI sequences) in detecting sites of disease in adult patients with lymphoma compared with the current standard of care, PET/CT. Secondary aims were to assess the additional value of diffusion-weighted imaging to PET/MRI in disease detection and to evaluate the relationship between the standardized uptake value on PET/MR and the apparent diffusion coefficient on diffusion-weighted imaging. Methods Sixty-eight studies in 66 consecutive patients with histologically proven Hodgkin or non-Hodgkin lymphoma were prospectively evaluated. Each patient had whole body PET/CT, followed by whole body PET/MR. Two experienced readers independently evaluated the PET/MRI studies, and two other experienced readers independently evaluated PET/CT. Site of lymphoma involvement and SUVmax at all nodal sites more avid than background liver were recorded. Readers provided stage (in baseline cases) and disease status (remission vs active disease). The apparent diffusion coefficient mean value corresponding to the most avid PET site of disease was recorded. Results Ninety-five nodal and 8 extranodal sites were identified on both PET/CT and PET/MRI. In addition, 3 nodal and 1 extranodal sites were identified on PET/MRI. For positive lesion detection, reader agreement in PET/MR was perfect between the 2 readers and almost perfect between PET/CT and PET/MR (k > 0.978). Intermodality agreement between PET/CT and PET/MRI was also near perfect to perfect for staging/disease status k = (0.979–1.000). SUVmax from PET/CT and PET/MRI correlated significantly (Spearman rho correlation coefficient, 0.842; P < 0.001). Diffusion-weighted imaging did not alter lesion detection or staging in any case. A negative correlation was demonstrated between ADC mean and SUVmax (Spearman rho correlation coefficient r, −0.642; P < 0.001). Conclusions PET/MRI is a reliable alternative to PET/CT in the evaluation of patients with lymphoma. Diffusion-weighted imaging did not alter diagnostic accuracy. With comparable accuracy in detection of disease sites and added benefit of radiation dose reduction, PET/MRI has a potential to become part of routine lymphoma imaging.

The production of JAK2 wild‐type platelets is not downregulated in patients with JAK2 V617F mutant‐positive essential thrombocythaemia

To clarify the relationship between the levels of JAK2 wild‐type (WT) and V617F mutant‐positive platelets in patients with essential thrombocythaemia (ET), we quantified mutant levels in purified cells from 10 V617F‐positive patients prior to receiving cytoreductive therapy. Mutant levels were significantly higher in platelet than neutrophil RNA (P = 0·002), but the mutation was still only present in a sub‐population of platelets (median 54%). When the absolute number of WT platelets was calculated, it was always within or above the normal platelet range, indicating that there is an aberration in the negative feedback to JAK2 WT platelets in ET.

Guidelines for the investigation and management of nodular lymphocyte predominant Hodgkin lymphoma.

Department of Haematology, Beatson West of Scotland Cancer Centre, Gartnavel Hospital, Glasgow, PETIC, Department of Radiology, University Hospital of Wales, Department of Clinical Oncology, Velindre Cancer Centre, Cardiff, UK, Paediatric Haematology/Oncology Unit, Children’s Hospital, John Radcliffe Hospital, Headington, Oxford, Department of Haematology, University College London Hospitals, Department of Pathology, University College London Hospitals, and Department of Haematology, The Royal Free London NHS Trust, London, UK

Ofatumumab is a feasible alternative anti-CD20 therapy in patients intolerant of rituximab

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Both native and ectopically transplanted hearts shown on FDG PET/CT in a PTLD patient.

Posttransplant lymphoproliferative disorder (PTLD) is one of the unfortunate complications of immunosuppression after allograft transplantation. 18F-FDG PET/CT plays an important role in the diagnosis and management of PTLD. The authors report a PET/CT scan of a young woman who received a heterotopic cardiac transplant, demonstrating 2 functional hearts in the thorax. The scan also demonstrates a small-volume mediastinal lymphadenopathy caused by the PTLD/B-cell lymphoma, subsequently proven by mediastinoscopic biopsy.