Page 133 - 2019_04-Haematologica-web

Thromboembolism and thromboprophylaxis in pediatric ALL
A
B
C
D
E
F
Figure 2. Thromboembolic events according to the randomization arms. Results are shown by intention to treat (A, C and E) and by treatment as given (B, D and F) for the total cohort (A and B) and stratified by age <6 years (C and D) and ≥6 years (E and F). Events are depicted as cumulative incidence curves. The P values indicated were calculated with the Fisher exact test. CI: confidence interval; OR: odds ratio; TE: thromboembolism; UFH: unfractionated heparin.
Exploratory as-treated analyses stratified by age (Figure 2D,F) demonstrated a significantly reduced risk of throm- boembolism in patients 6 years of age or older when treated in one of the experimental arms compared to the risk in the control group [UFH: 18/158, 11.4%; enoxa- parin: 5/120, 4.2%, P(versus UFH)=0.001; antithrombin 4/150, 2.7%, P(versus UFH)<0.001]. No significant differ- ences were found among patients below 6 years of age (UFH 7/214, 3.3%; enoxaparin 2/96, 2.1%; antithrombin 5/191, 2.6%).
No formal test for interaction was done for the sub- group analysis by age. Applying Fine-Gray models with interaction terms for age older than 6 years and enoxa- parin/antithrombin, the interactions were not significant. This, however, does not entirely exclude interactions since the power of such tests is low.
Hemorrhage
Eight bleeding episodes were documented among the 949 randomized patients (0.9%). Four of them occurred during induction chemotherapy under antithrombotic prophylaxis and four during consolidation after termina- tion of the anticoagulants. All hemorrhages were classi- fied as major (7 gastrointestinal, 1 cerebral). Four patients with hemorrhage were treated in the UFH group (1.1%), three in the antithrombin group [0.9%, P(versus UFH)=1.0] and one patient in the enoxaparin group [0.5%, P(versus UFH)=0.66].
Leukemia outcome and survival
The 5-year probability of event-free survival and cumu- lative incidence of relapse of the THROMBOTECT cohort were comparable to those of the 577 non-random-
haematologica | 2019; 104(4)
761