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Cerebral Sinovenous Thrombosis and Asparaginase Re-exposure in Patients Aged 1 to 45 Years with Acute Lymphoblastic Leukemia: A NOPHO ALL2008 Study

1Pediatrics and Adolescent Medicine, Aarhus University Hospital, Aarhus, Denmark, 2Pediatric Oncology Research Laboratory, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark, 3Department of Hematology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark, 4Department of Paediatrics and Adolescent Medicine, Rigshospitalet, Copenhagen, Denmark, 5Department of Clinical Medicine, Aarhus University, Aarhus, Denmark, 6Section of Paediatric Haematology & Oncology, Rigshospitalet, Copenhagen, Denmark

Abstract Number: LPB0076

Meeting: ISTH 2021 Congress

Theme: Pediatrics » Thrombosis in Neonates and Children

Background: Cerebral sinovenous thrombosis (CSVT) is a serious complication of acute lymphoblastic leukemia (ALL) therapy. Asparaginase (ASP), a cornerstone in ALL treatment, is associated with increased risk of CSVT. CSVT-related premature truncation of ASP may impact survival rates.

Aims: To explore

  • incidence of ASP truncation after CSVT in ALL patients
  • potential clinical and imaging factors predictive of ASP truncation
  • CSVT sequelae

Methods: We included patients (1‒45 years, n=2400) treated according to the NOPHO ALL2008 protocol from 2008/7‒2018/10. Data were retrospectively collected from medical charts. Informed consent was obtained and the study was approved by the local ethics committees.

Results: We identified 45 patients with CSVT, corresponding to a prevalence of 1.9% (95%-CI:1.4‒2.5%). Patients with CSVT were older (33% adolescents/10‒17.9 years; 22% adults/≥18 years), and 22% had CNS leukemia at ALL diagnosis, compared with patients without thromboembolism (16%, 14% and 12%, respectively) (p<0.01). Three patients (7%) died due to CSVT.
Twenty-nine patients (66%) were re-exposed to ASP a median of 33 days after CSVT, all under anticoagulation cover. Thirty-four (83%) had ≥1 ASP dose omitted. Patients re-exposed and non-re-exposed had a median of 2 and 6 doses omitted, respectively. Two patients (4%) experienced re-thrombosis after ASP re-exposure. No re-thrombosis among non-re-exposed patients. Re-exposed patients performed better on the Modified Rankin Scale (mRS) compared to non-re-exposed (2.0 versus 2.7, p<0.05) at CSVT diagnosis. No neurological findings predicted re-exposure. CSVT-score by Zubkov AY et al. quantifying CSVT extension showed no difference among re-exposed and non-re-exposed patients at CSVT diagnosis (2.3 versus 2.9, p=0.16) nor at last follow-up (0.6 versus 0.8, p=0.21). No difference was detected applying mRS among re- and non-re-exposed patients (0.38 and 0.45, p=0.08) at last follow-up (mean 5.8 years).

Conclusions: Although 66% of ALL patients diagnosed with CSVT were re-exposed to ASP, a low recurrence of thrombosis (4%) was detected.

To cite this abstract in AMA style:

Skipper MT, Rank CU, Andrés-Jensen L, Schmiegelow K, Albertsen BK, Tuckuviene R, NOPHO Thrombosis and Haemostasis Working group . Cerebral Sinovenous Thrombosis and Asparaginase Re-exposure in Patients Aged 1 to 45 Years with Acute Lymphoblastic Leukemia: A NOPHO ALL2008 Study [abstract]. Res Pract Thromb Haemost. 2021; 5 (Suppl 2). https://abstracts.isth.org/abstract/cerebral-sinovenous-thrombosis-and-asparaginase-re-exposure-in-patients-aged-1-to-45-years-with-acute-lymphoblastic-leukemia-a-nopho-all2008-study/. Accessed December 7, 2021.

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