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Multicenter Study
. 2010 Jun 17;115(24):4999-5004.
doi: 10.1182/blood-2010-01-263012. Epub 2010 Mar 25.

Validation of a predictive model for identifying an increased risk for thromboembolism in children with acute lymphoblastic leukemia: results of a multicenter cohort study

Lesley Mitchell  1 , Moritz Lambers, Silke Flege, Gili Kenet, Valerie Li-Thiao-Te, Susanne Holzhauer, Christoph Bidlingmaier, Michael C Frühwald, Christine Heller, Wolfgang Schmidt, Brigitte Pautard, Ulrike Nowak-Göttl
Affiliations
Multicenter Study

Validation of a predictive model for identifying an increased risk for thromboembolism in children with acute lymphoblastic leukemia: results of a multicenter cohort study

Lesley Mitchell et al. Blood. .

Abstract

Among risk factors for developing thromboembolism (VTE) in children with acute lymphoblastic leukemia were Escherichia coli asparaginase, concomitant steroid use, presence of central venous lines, and thrombophilic abnormalities. Developing a predictive model for determining children at increased risk would be beneficial in targeting interventional studies to high-risk groups (HRGs). Predictive variables were incorporated into a risk assessment model, which was evaluated in 456 children and then validated in 339 patients. VTE risk by score was no greater than 2.5 for low-risk group (LRG) and greater than 2.5 for HRG. VTE rates at 3.5 months (validation cohorts) were 2.5% in LRG and 64.7% in HRG. In multivariate analysis adjusted for age, duration of asparaginase administration, enoxaparin prophylaxis, and T-immunophenotype, the HRG was significantly associated with VTE compared with the LRG (hazard/95% confidence interval [CI], 8.22/1.85-36.53). Model specificity was 96.2% and sensitivity was 63.2%. As secondary objective we investigated the use of enoxaparin for VTE prophylaxis in the HRG. HRG patients without enoxaparin prophylaxis showed a significantly reduced thrombosis-free survival compared with children on low-molecular-weight heparin (LMWH). On the basis of the high specificity, the model may identify children with leukemia at risk of VTE. LMWH may help prevent VTE in the HRG; this warrants assessment in larger cooperative clinical trials.

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Figures

Figure 1
Figure 1
Thromboses-prone drugs, administration days, single and cumulative doses according to different ALL-induction protocols are shown. In the BFM-95 protocol (*) DNR was administered twice (days 8 and 15), and in the 2000 study on days 8, 15, 22, and 29. In addition, in the BFM 2000 protocol PDN and DEXA were randomized. In the FRALLE 2000 HRG (dashed arrow), children received PDN instead of DEXA, and ASP was started on day 8 instead of day 10. ALL indicates acute lymphoblastic leukemia; ASP, Escherichia coli asparaginase; D, day; DEXA, dexamethasone; DNR, daunorubicin; HR, high risk; PDN, prednisone; SR, standard risk; and VCR, vincristine.
Figure 2
Figure 2
The study flow chart is depicted.
Figure 3
Figure 3
The probability of TSF as a function of time is shown. Children with ALL grouped above the score of 2.5 (▲) showed a significantly reduced thrombosis-free survival (TFS) than children with a risk score less than 2.5 (●).
Figure 4
Figure 4
The TFS in children with enoxaparin prophylaxis compared with patients without prophylaxis is shown. Children with ALL without prophylaxis (▼) showed a significantly reduced TFS than children with prophylactic low-molecular-weight heparin (LMWH; ●).
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