Patency and reflux in relation to post-thrombotic syndrome: a subanalysis of the Ultrasound-Accelerated Catheter-Directed Thrombolysis Versus Anticoagulation for the Prevention of Post-Thrombotic Syndrome trial.

BACKGROUND: Adjunctive catheter-directed thrombolysis (CDT) shows variable efficacy in preventing postthrombotic syndrome (PTS), despite restored patency. OBJECTIVES: This CAVA-trial subanalysis investigated the effect of ultrasound accelerated (UA)CDT on patency, reflux and their relevance in PTS development. METHODS: This multicentre, randomised, single-blind trial, enrolled patients (18-85 years), with a first iliofemoral deep vein thrombosis (DVT) and symptom duration ≤14 days. Patency and reflux were assessed by duplex ultrasound (DUS) at 12 months (T12) and long-term (LT) follow-up (median 39.5 (24.0-63.0) months). PTS was diagnosed using the Villalta score. RESULTS: UACDT significantly improved patency in all vein segments at T12 (60.3% UACDT vs. 25.9% standard treatment (ST), p=0.002) and LT (45.2% UACDT vs. 11.9% ST, p<0.001). Popliteal patency, however, was similar between groups (87.9% UACDT vs. 83.3% ST, p=0.487). Reflux was similar between groups at T12 and LT, only popliteal reflux was significantly reduced in the UACDT group at LT (22.6% UACDT vs. 44.8% ST, p=0.010). Absent iliac patency at T12 was associated with increased PTS risk in the ST-group only (OR 10.84 [1.93-60.78]; p=0.007). In the UACDT group popliteal reflux at T12 was associated with moderate-severe PTS at T12 (OR 4.88 [1.10-21.57]; p=0.041) and LT (OR 5.83 [1.44-23.63]; p=0009). Combined popliteal reflux and absent iliac patency significantly amplified PTS risk (OR 10.79 [2.41-48.42]; p<0.001). CONCLUSION: UACDT improves patency and reduced popliteal reflux. Iliac patency and popliteal reflux are independently associated with moderate-severe PTS and contribute synergistically to its development. However, a proportion of moderate-severe PTS cases lacks an evident underlying cause.

Inferior Outcome of Addition of the Aminopeptidase Inhibitor Tosedostat to Standard Intensive Treatment for Elderly Patients with AML and High Risk MDS.

Treatment results of AML in elderly patients are unsatisfactory. We hypothesized that addition of tosedostat, an aminopeptidase inhibitor, to intensive chemotherapy may improve outcome in this population. After establishing a safe dose in a run-in phase of the study in 22 patients, 231 eligible patients with AML above 65 years of age (median 70, range 66-81) were randomly assigned in this open label randomized Phase II study to receive standard chemotherapy (3+7) with or without tosedostat at the selected daily dose of 120 mg (n = 116), days 1-21. In the second cycle, patients received cytarabine 1000 mg/m2 twice daily on days 1-6 with or without tosedostat. CR/CRi rates in the 2 arms were not significantly different (69% (95% C.I. 60-77%) vs 64% (55-73%), respectively). At 24 months, event-free survival (EFS) was 20% for the standard arm versus 12% for the tosedostat arm (Cox-p = 0.01) and overall survival (OS) 33% vs 18% respectively (p = 0.006). Infectious complications accounted for an increased early death rate in the tosedostat arm. Atrial fibrillation was more common in the tosedostat arm as well. The results of the present study show that the addition of tosedostat to standard chemotherapy does negatively affect the therapeutic outcome of elderly AML patients.