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Thromboembolism in acute lymphoblastic leukemia : Results of nopho all2008 protocol treatment in patients aged 1 to 45 years

Rank, Cecilie Utke ; Toft, Nina ; Tuckuviene, Ruta ; Grell, Kathrine ; Nielsen, Ove Juul ; Frandsen, Thomas Leth ; Marquart, Hanne Vibeke Hansen ; Albertsen, Birgitte Klug ; Tedgård, Ulf LU and Hallböök, Helene , et al. (2018) In Blood 131(22). p.2475-2484
Abstract

Thromboembolism frequently occurs during acute lymphoblastic leukemia (ALL) therapy. We prospectively registered thromboembolic events during the treatment of 1772 consecutive Nordic/Baltic patients with ALL aged 1 to 45 years who were treated according to the Nordic Society of Pediatric Hematology and Oncology ALL2008 protocol (July 2008-April 2017). The 2.5-year cumulative incidence of thromboembolism (N 5 137) was 7.9% (95% confidence interval [CI], 6.6-9.1); it was higher in patients aged at least 10 years (P < .0001). Adjusted hazard ratios (HRas) were associated with greater age (range, 10.0-17.9 years: HRa, 4.9 [95% CI, 3.1-7.8; P < .0001]; 18.0-45.9 years: HRa, 6.06 [95% CI, 3.65-10.1; P < .0001]) and mediastinal mass... (More)

Thromboembolism frequently occurs during acute lymphoblastic leukemia (ALL) therapy. We prospectively registered thromboembolic events during the treatment of 1772 consecutive Nordic/Baltic patients with ALL aged 1 to 45 years who were treated according to the Nordic Society of Pediatric Hematology and Oncology ALL2008 protocol (July 2008-April 2017). The 2.5-year cumulative incidence of thromboembolism (N 5 137) was 7.9% (95% confidence interval [CI], 6.6-9.1); it was higher in patients aged at least 10 years (P < .0001). Adjusted hazard ratios (HRas) were associated with greater age (range, 10.0-17.9 years: HRa, 4.9 [95% CI, 3.1-7.8; P < .0001]; 18.0-45.9 years: HRa, 6.06 [95% CI, 3.65-10.1; P < .0001]) and mediastinal mass at ALL diagnosis (HRa, 2.1; 95% CI, 1.0-4.3; P 5 .04). In a multiple absolute risk regression model addressing 3 thromboembolism risk factors, age at least 10 years had the largest absolute risk ratio (RRage, 4.7 [95% CI, 3.1-7.1]; RRenlarged lymph nodes, 2.0 [95% CI, 1.2-3.1]; RRmediastinal mass, 1.6 [95% CI, 1.0-2.6]). Patients aged 18.0 to 45.9 years had an increased hazard of pulmonary embolism (HRa, 11.6; 95% CI, 4.02-33.7; P < .0001), and patients aged 10.0 to 17.9 years had an increased hazard of cerebral sinus venous thrombosis (HRa, 3.3; 95% CI, 1.5-7.3; P 5 .003) compared with children younger than 10.0 years. Asparaginase was truncated in 38/128 patients with thromboembolism, whereas thromboembolism diagnosis was unassociated with increased hazard of relapse (P 5 .6). Five deaths were attributable to thromboembolism, and patients younger than 18.0 years with thromboembolism had increased hazard of dying compared with same-aged patients without thromboembolism (both P £ .01). In conclusion, patients aged at least 10 years could be candidates for preemptive antithrombotic prophylaxis. However, the predictive value of age 10 years or older, enlarged lymph nodes, and mediastinal mass remain to be validated in another cohort.

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type
Contribution to journal
publication status
published
subject
in
Blood
volume
131
issue
22
pages
10 pages
publisher
American Society of Hematology
external identifiers
  • pmid:29661787
  • scopus:85048188042
ISSN
0006-4971
DOI
10.1182/blood-2018-01-827949
language
English
LU publication?
no
id
6e5e5240-ad58-42b4-9c0e-0e3f7059d1d3
date added to LUP
2018-06-21 15:19:49
date last changed
2022-08-02 21:04:38
@article{6e5e5240-ad58-42b4-9c0e-0e3f7059d1d3,
  abstract     = {{<p>Thromboembolism frequently occurs during acute lymphoblastic leukemia (ALL) therapy. We prospectively registered thromboembolic events during the treatment of 1772 consecutive Nordic/Baltic patients with ALL aged 1 to 45 years who were treated according to the Nordic Society of Pediatric Hematology and Oncology ALL2008 protocol (July 2008-April 2017). The 2.5-year cumulative incidence of thromboembolism (N 5 137) was 7.9% (95% confidence interval [CI], 6.6-9.1); it was higher in patients aged at least 10 years (P &lt; .0001). Adjusted hazard ratios (HRas) were associated with greater age (range, 10.0-17.9 years: HRa, 4.9 [95% CI, 3.1-7.8; P &lt; .0001]; 18.0-45.9 years: HRa, 6.06 [95% CI, 3.65-10.1; P &lt; .0001]) and mediastinal mass at ALL diagnosis (HRa, 2.1; 95% CI, 1.0-4.3; P 5 .04). In a multiple absolute risk regression model addressing 3 thromboembolism risk factors, age at least 10 years had the largest absolute risk ratio (RR<sub>age</sub>, 4.7 [95% CI, 3.1-7.1]; RR<sub>enlarged</sub> lymph nodes, 2.0 [95% CI, 1.2-3.1]; RR<sub>mediastinal</sub> mass, 1.6 [95% CI, 1.0-2.6]). Patients aged 18.0 to 45.9 years had an increased hazard of pulmonary embolism (HRa, 11.6; 95% CI, 4.02-33.7; P &lt; .0001), and patients aged 10.0 to 17.9 years had an increased hazard of cerebral sinus venous thrombosis (HRa, 3.3; 95% CI, 1.5-7.3; P 5 .003) compared with children younger than 10.0 years. Asparaginase was truncated in 38/128 patients with thromboembolism, whereas thromboembolism diagnosis was unassociated with increased hazard of relapse (P 5 .6). Five deaths were attributable to thromboembolism, and patients younger than 18.0 years with thromboembolism had increased hazard of dying compared with same-aged patients without thromboembolism (both P £ .01). In conclusion, patients aged at least 10 years could be candidates for preemptive antithrombotic prophylaxis. However, the predictive value of age 10 years or older, enlarged lymph nodes, and mediastinal mass remain to be validated in another cohort.</p>}},
  author       = {{Rank, Cecilie Utke and Toft, Nina and Tuckuviene, Ruta and Grell, Kathrine and Nielsen, Ove Juul and Frandsen, Thomas Leth and Marquart, Hanne Vibeke Hansen and Albertsen, Birgitte Klug and Tedgård, Ulf and Hallböök, Helene and Ruud, Ellen and Jarvis, Kirsten Brunsvig and Quist-Paulsen, Petter and Huttunen, Pasi and Wartiovaara-Kautto, Ulla and Jónsson, Ólafur Gísli and Trakymiene, Sonata Saulyte and Griškevičius, Laimonas and Saks, Kadri and Punab, Mari and Schmiegelow, Kjeld}},
  issn         = {{0006-4971}},
  language     = {{eng}},
  month        = {{05}},
  number       = {{22}},
  pages        = {{2475--2484}},
  publisher    = {{American Society of Hematology}},
  series       = {{Blood}},
  title        = {{Thromboembolism in acute lymphoblastic leukemia : Results of nopho all2008 protocol treatment in patients aged 1 to 45 years}},
  url          = {{http://dx.doi.org/10.1182/blood-2018-01-827949}},
  doi          = {{10.1182/blood-2018-01-827949}},
  volume       = {{131}},
  year         = {{2018}},
}