Positron emission tomography (PET) is a whole-body imaging technique using 18 fluorine-fluorodeoxyglucose (FDG), whose uptake is increased in tumor cells. Published studies have shown PET to be an effective method of staging lymphoma and to be more sensitive than CT at detecting extranodal disease. The purpose of this study was to determine whether the increased marrow uptake of FDG observed in some lymphoma patients during routine staging PET scans represented marrow involvement by disease. PET scans of 50 patients with Hodgkin's (12) and non-Hodgkin's (38) lymphoma were analyzed by three independent observers and the marrow graded as normal or abnormal using a visual grading system. Unilateral iliac crest marrow aspirates and biopsies were performed on all patients. The PET scan and marrow histology agreed in 39 patients (78%), being concordant positive in 13 and concordant negative in 26 patients. In 8 patients the PET scan showed increased FDG uptake but staging biopsy was negative; in 4 of these 8 patients the PET scan showed a normal marrow background with focal FDG “hot spots” distant from the site biopsied. In 3 patients the marrow biopsy specimen was positive but the PET scan normal; 2 of these 3 patients had non-Hodgkin's lymphoma whose malignant cells did not take up FDG at lymph node or marrow disease sites. Therefore, there were only 5 patients (10%) in whom there was a difference between the PET scan and biopsy result which could not be fully explained. Visual interpretation of marrow FDG uptake during whole-body staging PET scans can correctly assess marrow disease status in a high proportion of lymphoma patients. PET has the potential to reduce the need for staging marrow biopsy.

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Most cases of mastocytosis are indolent, usually cutaneous mastocytosis or indolent systemic mastocytosis (SM). Aggressive mast cell (MC) diseases are very rare and often fatal. They can develop de novo or due to progression of indolent forms and can present in different ways; either as MC sarcoma or as advanced SM which includes aggressive SM, MC leukemia, and SM with an associated hematological neoplasm. This review will describe these different aggressive forms of mastocytosis, illustrated by cases submitted to the workshop of the 18th Meeting of the European Association for Haematopathology, Basel 2016, organized by the European Bone Marrow Working Group. In addition, the diagnostic criteria for identifying myelomastocytic leukemia, an aggressive myeloid neoplasm with partial MC differentiation that falls short of the criteria for SM, and disease progression in patients with established mastocytosis are discussed.

1746 Introduction: Systemic Mastocytosis (SM) is a myeloproliferative neoplasm (MPN) with heterogeneous clinical manifestations and limited treatment options for patients with aggressive disease. The WHO Classification sub divides SM patients into Indolent (ISM: evidence of clonal mast cells in bone marrow), Smouldering (SSM: Trypstase > 200ng/ml;organomegaly without dysfunction; bone marrow mast cell burden > 30% ), Aggressive (ASM: organomegaly with laboratory evidence of dysfunction), Mast Cell Leukaemia (MCL; > 20% mast cells on aspirate and >10% on blood film) and Associated Haematological Non-Mast Cell Disorders (AHNMD). The c-kit mutation (D816V) is present in > 90% of SM patients. Tryptase levels reflect total mast cell burden. To date there is no discriminatory marker to allow for identification of SM patients with more aggressive disease. CD30 (Ki-I antigen) has been reported as a potential marker for mast cells in high grade mastocytosis (Sotlar et al, 2011).We present preliminary data on 43 SM patients seen at Guys and St Thomas' Hospitals NHS Foundation Trust looking at CD30 and CD123 expression with clinical correlates. Methodology: 43/58 SM patients who have a full set of clinical records and bone marrow trephine samples have been evaluated. Bone marrow trephine processing: fixation in a neutral buffered formalin < 24hours; EDTA decalcification for 48 hours;Immunochemistry on an automated immunostainer (Leica Bondmax)using standard protocols: CD 30 (Dako dilution 1:75, antigen retrieval ER2). CD123 (BD Sciences, Novacastra, dilution 1:400,antigen retrieval ER2). Bone Marrow trephine samples were reviewed by haematopathologists at diagnostic MDM. Disease bulk was estimated as a percentage of the trephine sample. Immunocytochemistry review of the CD30/CD123 was reviewed by a single haematopathologist for this study. Clinical information was reviewed for laboratory results, tryptase levels, clinical symptoms and SM diagnosis. Results: 43 patients: M:F(18:25). SM diagnoses: 26 ISM (60%), 2 SSM (5%),3 ASM (7% ), 12 AHNMD (28%). Data on 43 patients for CD30 expression and 40 for CD123 expression. Tryptase: 20 CD30(+) patients median 74.9ng/ml (range 16.6–285ng/ml): 23 CD 30(−) patients median 43.6ng/ml (range 15.1–386ng/ml). Conclusions: Our preliminary data on 43 patients with SM/ CD30/123 expression suggests: Disclosures: Harrison: Novartis: Honoraria, Research Funding, Speakers Bureau; YM Bioscience: Consultancy, Honoraria; Sanofi Aventis: Honoraria; Shire: Honoraria, Research Funding.

Essential thrombocythemia (ET) is associated with arterial and venous thrombosis, hemorrhage and transformation to acute leukemia and myelofibrosis. Cytoreduction with hydroxyurea (Hu) reduces thrombotic risk, but concerns about potential toxicity have led to the widespread use of a newer agent, anagrelide (Ag) as first-line therapy. However, no randomized trials comparing the efficacy and safety of Ag with Hu have been performed. The MRC PT1 trial is an international, multi-centre, randomized controlled trial comparing Ag with Hu in patients with ET at high-risk of vascular events (based on age, platelet count or cardiovascular risk factors). The trial was independently conceived, conducted and analysed by the investigators on behalf of the UK Myeloproliferative Disorders Study Group and the MRC Adult Leukaemia Working Party. Patients (newly diagnosed or previously treated) were randomized to receive either Ag plus aspirin (Ag+asp) or Hu+asp. Clinical end-points together with blood and bone marrow morphology were assessed centrally by experts blinded to treatment allocation. With 809 patients randomized and median follow-up of 39 months, it is the largest and most comprehensive randomized study of ET performed to date. Patients in the Ag+asp arm were significantly more likely to reach the primary end-point and several secondary end-points. Intention-to-treat log-rank analyses of time to event indicate that Ag+asp patients were significantly more likely than Hu+asp patients to reach the composite primary end-point of arterial thrombosis, venous thrombosis or major hemorrhage (55 v 36 events; odds ratio 1.57; 95% CI 1.04–2.37; p=0.03). Ag+asp was also associated with increased rates of arterial thrombosis (37 v 17 events; OR 2.16; 95% CI 1.27–3.69; p=0.004) and major hemorrhage (22 v 8 events; OR 2.61; CI 1.27–5.33; p=0.008) but, interestingly, decreased venous thrombosis compared to Hu+asp (3 v 14 events; OR 0.27; CI 0.11–0.71; p=0.006). Myelofibrotic transformation, the diagnosis of which required new clinical and/or laboratory features in addition to grade III/IV reticulin fibrosis, was significantly increased in the Ag+asp arm (16 v 5 events; OR 2.92, CI 1.24–6.86, p=0.01). Transformation to MDS/AML was comparable between the two arms (4 Ag+asp v 6 Hu+asp), although the small number of transformations and short follow-up prevent firm conclusions about leukemogenicity. Overall survival was not statistically different. Ag+asp was more poorly tolerated than Hu+asp. In the Ag+asp arm significantly fewer patients remained on their allocated treatment (p<0.00001) and there were significantly greater rates of cardiovascular (p<0.0001), gastrointestinal (p=0.02), neurological (p<0.0001) and constitutional (p<0.001) side effects. Long-term control of the platelet count was comparable between the two arms. These results demonstrate that, compared to Hu+asp, Ag+asp is associated with an excess rate of arterial thrombosis, major hemorrhage and myelofibrotic transformation but decreased venous thrombosis, and suggest that Hu should remain first-line therapy in patients with ET at high risk for vascular events.