Treatment practice and outcomes in FLT3-mutant acute myeloid leukemia in the pre-midostaurin era: a real-world experience from Australian tertiary hospitals.

Recent regulatory approval of midostaurin, a FLT3 targeting small molecular inhibitor, will likely lead to increased use of midostaurin in combination with intensive chemotherapy for patients with FLT3-mutant AML. Translation of clinical trial results into everyday practice has its challenges. This study compared the relevance of the trial population and practices studied in the midostaurin registration study (RATIFY) with real-world practice in terms of patient factors, chemotherapy, mutation-specific frequencies and clinical outcomes among patients with FLT3-mutant AML in the pre-midostaurin era (2010-2015) in Australia. We observed substantial diversity of chemotherapy regimens used in the community and limitations of the generalizability of eligibility criteria used in RATIFY (such as age and hyperleukocytosis). This study provides real-world historical data that may be used for comparison with future trial cohorts incorporating FLT3 inhibitors into the management of FLT3-mutant AML and highlights the inherent difficulties in translating clinical trial data into routine practice.

Venous thromboembolism management in Northeast Melbourne: how does it compare to international guidelines and data?

BACKGROUND: Venous thromboembolism (VTE) is a major cause of morbidity and mortality with significant heterogeneity in its management, both within our local practice and in international guidelines. AIMS: To provide a holistic evaluation of 'real-world' Australian experience in the warfarin era, including how we compare to international guidelines. METHODS: Retrospective evaluation of VTE from July 2011 to December 2012 at two major hospitals in Melbourne, Australia. These results were compared to recommendations in the international guidelines. RESULTS: A total of 752 episodes involving 742 patients was identified. Contrary to international guidelines, an unwarranted heritable thrombophilia screen was performed in 22.0% of patients, amounting to a cost of AU$29 000. The duration of anticoagulation was longer compared to international recommendations, although the overall recurrence (3.2/100 person-years) and clinically significant bleeding rates (2.4/100 person-years) were comparable to 'real-world' data. Unprovoked VTE (hazard ratio 2.06; P = 0.01) was a risk factor for recurrence, and there was no difference in recurrence between major VTE (proximal deep vein thrombosis (DVT) and/or pulmonary embolism) and isolated distal DVT (3.02 vs 3.94/100 person-years; P = 0.25). Fourteen patients were subsequently diagnosed with malignancy, and patients with recurrent VTE had increased risk of prospective cancer diagnosis (relative risk 6.68; P < 0.001). CONCLUSIONS: While our 'real-world' VTE experience during the warfarin era largely correlates with international guidelines, there remains heterogeneity in the management strategies, including excessive thrombophilia screening and longer duration of anticoagulation. This audit highlights the need for national VTE guidelines, as well as prospective auditing of VTE management, in the direct oral anticoagulant era for future comparison.

Retrospective review on isolated distal deep vein thrombosis (IDDVT) - A benign entity or not?

INTRODUCTION: Isolated distal deep venous thrombosis (IDDVT) is traditionally associated with less severe clinical sequelae, with ongoing debate on multiple aspects of its management. Despite numerous studies evaluating its acute management, there remains a paucity of data evaluating long-term complications such as recurrence and subsequent malignancy. We aim to evaluate the characteristics of IDDVT in institutions that routinely perform whole leg ultrasonography, and the risks of recurrence and complications in comparison to major venous thromboembolism (major VTE; defined as above-knee or proximal DVT and pulmonary embolism (PE)). METHODS: Retrospective evaluation of consecutive IDDVT and major VTE from July 2011 to December 2012 in a hospital network in Melbourne, Australia. Patients were followed up for a minimum of 24months. Patients with active malignancy were excluded. RESULTS: Of 1024 VTE cases, there were 164 non-cancer patients (92 males, 72 females, median age of 61years) with IDDVT. Compared to major VTE, IDDVT was more likely to be provoked (73% vs 59%, p<0.01), has shorter duration of anticoagulation (median 3.5months vs 6.0months, p<0.01) and less clinically significant bleeding (2.4% vs 6.7%, p=0.05), independent of duration of therapy. Recurrence was non-inferior compared to major VTE (10% vs 7%, p=0.36) and 60% recurred with major VTE. Three (1.8%) were subsequently diagnosed with cancer (vs 1.9% in major VTE, p=0.97). CONCLUSIONS: IDDVT has non-inferior rates of recurrence and subsequent cancer detection compared to major VTE and hence, its clinical significance should not differ from major VTE. Further studies are required to determine the adequate length of anticoagulation.