PracticeUpdate: Haematology & Oncology

CONFERENCE COVERAGE 20

Patients who reached target second- maintenance-dose antithrombin III level achieved complete response of veno-occlusive disease A large percentage of patients who reached target second-maintenance- dose antithrombin III level achieved

second maintenance dose level, five received adjusted doses and two (40.0%) reached target level before the fourth escalated dose. Thirteen patients (68.4%) achieved complete response at a median of 18 (range 6–54) days from treatment. A greater percentage of patients who reached target second maintenance dose level, versus those who did not, achieved complete response (n=11/12, 91.7% vs n=2/7, 28.6%). Two patients experienced adverse events (grade 4 haemoptysis and grade 5 pulmonary haemorrhage) related to antithrombin-III treatment. At a median follow-up of 65 (range 4–395) days from treatment, the probability of death from veno-occlusive disease or veno-occlusive disease-related organ failure or a complication related to antithrombin-III treatment was 29.4%. Three patients died of veno-occlusive disease or veno-occlusive disease-related organ failure at a median of 22 days from treatment. One patient died of antithrombin-III-related pulmonary haemorrhage at 26 days from treatment. The probability of death from veno-occlusive disease/veno-occlusive disease-related organ failure or treatment complication was lower in patients who reached target second maintenance dose level than in those who did not (20.0% vs 42.9%, difference not significant). Dr Shin concluded that a large percentage of patients who reached target second- maintenance-dose antithrombin-III level achieved complete response. Additional treatment strategies may be needed, however, for patients who do not reach the target second- maintenance-dose antithrombin-III level with their current antithrombin-III dosage.

been reached. The maintenance dose was adjusted to 50 × weight in kilograms + 120 – the second maintenance dose level × weight in kilograms /1.4 IU every 24 h if the target level was not reached. Antithrombin-III treatment was continued until complete response (disappearance of all parameters of veno-occlusive disease), or up to 2 weeks if veno-occlusive disease continued to progress. Twenty patients were enrolled and 19 (11 male, 8 female) were eligible for analysis. Patients underwent HSCT at a median age of 20.8 years for haematologic malignancies, solid tumours, and non-malignant diseases. Sixteen patients received busulfan and/or total body irradiation containing conditioning. Patients were diagnosed with veno-occlusive disease at median (range 6–30) day 18, and two patients suffered concomitant organ failure. Antithrombin-III treatment was started at median (range 0–6) day 0 from diagnosis of veno-occlusive disease. Median antithrombin-III level was 67% (range 46– 99%) before the start of treatment. Twelve patients (63.2%) reached target second maintenance dose level with treatment. Ten of these 12 patients received more than six maintenance doses and all maintained target level before the sixth maintenance dose. Of the seven patients who did not reach target

complete response of veno-occlusive disease caused by haematopoietic stem cell transplantation. This outcome of a multicentre, prospective, phase 2 study of antithrombin III-based treatment for veno- occlusive disease after haematopoietic stem cell transplantation (HSCT) was reported ASH 2016. Hee Young Shin, MD, PhD, of Seoul National University College of Medicine, South Korea, explained that endothelial injury of sinusoids and hepatic veins is the initial event in veno-occlusive disease. This injury results in activation of the coagulation cascade and inflammatory processes, which in turn lead to a hypercoagulable state and consumption of natural anticoagulants including antithrombin-III. Coagulopathy due to veno-occlusive disease can lead to multi-organ failure and death. Supplementation with antithrombin-III concentrate has been shown to reduce veno- occlusive disease-related mortality in several studies. Dr Shin and colleagues set out to evaluate the efficacy and safety of antithrombin-III- based treatment for veno-occlusive disease after HSCT. Between 2013 and 2015, patients with veno-occlusive disease were enrolled from five centres to receive antithrombin-III- based treatment. Veno-occlusive disease was diagnosed without limitation of onset time, when patients had at least two of the following features: • Serum total bilirubin >2 mg/dL • Hepatomegaly or right upper quadrant pain of liver origin • Unexplained weight gain >2% over baseline. Prophylaxis and other treatments of veno- occlusive disease were allowed. Antithrombin- III was loaded at 50 IU per kilogram of body weight every 8 h three times and maintenance doses were given at 50 IU per kilogram of body weight every 24 h. Target antithrombin- III level was ≥ 120%. Antithrombin-III level was measured before the second maintenance dose. The same dose was continued if the target level had

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© ASH 2016/Todd Buchanan 2016

PRACTICEUPDATE HAEMATOLOGY & ONCOLOGY