Submitted April 6, 2006
Accepted May 2, 2006
Thrombotic complications in childhood acute lymphoblastic
leukemia. A meta-analysis of 17 prospective studies
comprising 1,752 pediatric patients
Vanesa Caruso, Licia Iacoviello*, Augusto Di Castelnuovo, Sergio Storti, Guglielmo Mariani, Giovanni de Gaetano, and Maria B Donati
Laboratory of Genetic & Environmental Epidemiology, Research Laboratories,Catholic University, Italy
Hematology-Oncology Unit, Centre for High Technology Research, Catholic University,Campobasso, Italy
Division of Hematology, L'Aquila University, L'Aquila, Italy
* Corresponding author; email: licia.iacoviello{at}rm.unicatt.it.
The risk of thrombosis in children with acute
lymphoblastic leukemia (ALL) reportedly ranges between
1% and 37%. Epidemiologic studies have usually been
hampered by small numbers, making accurate estimates of
thrombosis risk in ALL patients very difficult. The aim
of this study was to better estimate the frequency of
this complication and to define how the disease, its
treatment and the host contribute to its occurrence. We
made an attempt to combine and analyze all published
data on the association between pediatric ALL and
thrombosis, by using a meta-analytic method. The rate of
thrombosis in 1,752 children from 17 prospective studies
was 5.2%(95%CI 4.2-6.4). The risk varies depending on
several factors. Most of the events occurred during the
induction phase of therapy. Lower doses of asparaginase
(ASP) for long periods were associated with the highest
incidence of thrombosis, as were anthracyclines and
prednisone (instead of dexamethasone). The presence of
central lines and of thrombophilic genetic abnormalities
also appeared to be frequently associated to thrombosis.
In conclusion, the overall thrombotic risk in ALL
children was significant, and the subgroup analysis was
able to identify high risk individuals, a finding that
will hopefully guide future prospective studies aimed at
decreasing this risk.
