Low rate of severe venous thromboses in children with ALL treatment according to COALL-92 and -97 protocol

Mauz‐Körholz, Christine; Nürnberger, W.; Irsfeld, H.; Körholz, Dieter; Göbel, U.

doi:10.1055/s-2008-1043791

Cited by 10 publications

(11 citation statements)

References 7 publications

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“…Mauz-K ö rholz et al showed that the frequency of severe and most often catheter-related thromboses was 1,5 % in patients treated according to the COALL-92 and -97 protocols [5,6] . However, cerebral sinus thromboses are rare events during this treatment.…”

Section: Discussionmentioning

confidence: 99%

Cerebral Sinus Occlusion in a Boy Presenting with Asparaginase-Induced Hypertriglyceridemia

Dietel¹,

Bührdel²,

Hirsch³

et al. 2007

Klin Padiatr

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Cerebral sinus thrombosis is a rare but severe complication during treatment for acute lymphoblastic leukaemia (ALL). It mostly has been reported during treatment with asparaginase and dexamethasone. Hypertriglyceridemia has - albeit very rarely - also been associated with asparaginase therapy. The combination of cerebral sinus thrombosis and hypertriglyceridemia however, has not yet been reported. Here we describe a 15-year-old boy who presented with clinical symptoms and radiologic findings of a cerebral sinus thrombosis. In addition, a life-threatening hypertriglyceridemia was present. The complication was successfully treated by anticoagulation with low molecular weight heparin and the lipid regulator bezafibrate.

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Section: Discussionmentioning

confidence: 99%

Cerebral Sinus Occlusion in a Boy Presenting with Asparaginase-Induced Hypertriglyceridemia

Dietel¹,

Bührdel²,

Hirsch³

et al. 2007

Klin Padiatr

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“…A relatively low thrombotic risk associated with individual drugs or an inherited defect is amplified in combination with other risk factors. Used separately, asparaginase and steroids have a low risk of thrombosis but in combination the risk rises nearly 10‐fold as demonstrated by a retrospective comparison of the risk of symptomatic thrombosis in contemporaneously treated German patients on the Cooperative Acute Lymphoblastic Leukaemia (COALL) 92/97 protocols (1·5%) and those treated on BFM 90/95 (11%) (Mauz‐Korholz et al , 1999). A multi‐centre prospective study of 420 consecutive patients (BFM n = 300, COALL n = 120) subsequently confirmed these results (BFM = 11·6%, COALL = 2·5%, OR = 7·7, P = 0·005) (Nowak‐Gottl et al , 2001).…”

Section: Risk Factorsmentioning

confidence: 99%

“…More recent guidelines on oral anticoagulation and heparin use in adults are available from the British Committee for Standards in Haematology (BSCH) (Baglin et al , 2006). The efficacy and safety of anticoagulation in patients with leukaemia has been demonstrated in several series (Mauz‐Korholz et al , 1999; Imberti et al , 2004; Ziegler et al , 2005). In a retrospective study of 719 leukaemic patients, 14 of 15 patients with a thrombosis were anti‐coagulated without major bleeding problems (Ziegler et al , 2005).…”

Section: Investigation and Managementmentioning

confidence: 99%

Thrombosis and acute lymphoblastic leukaemia

2007

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Summary Venous thrombosis is more frequent in patients treated for acute lymphoblastic leukaemia (ALL) than other malignancies and has distinctive causes, clinical features and remedies. The reported incidence varies from 1% to 36%, depending on the chemotherapy protocol and whether the reported cases are symptomatic or detected on screening radiography. The risk is thought to arise from increased thrombin generation at diagnosis combined with reduced thrombin inhibitory capacity due to depletion of circulating anti‐thrombin (AT) by asparaginase. A number of patient and treatment variables have been reported to influence the risk of thrombosis including hereditary thrombophilia, early insertion of central venous catheters and exposure to a combination of steroids and asparaginase during induction. Erwinia asparaginase is associated with a lower risk of thrombosis compared with Escherichia coli asparaginase. The majority of symptomatic thromboses are related to central venous catheters and involve the upper venous system. Central nervous system thrombosis involving the cerebral venous sinuses is a unique feature of asparaginase‐related thrombosis and is reported to occur in 1–3% of patients. Conclusive evidence to support the use of anti‐coagulant treatment or AT concentrates for primary prevention is lacking, as is evidence for the efficacy of AT concentrates in the management of established thrombosis. Preventative strategies are hampered by conflicting data on factors that would enable identification of those at highest risk of thrombosis.

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“…However, papers dealing with thrombosis and acute leukemia report almost exclusively anecdotical cases or uncontrolled historical series. Only five controlled patient series specifically aimed to evaluate the incidence of thrombosis have been published, all concerning ALL patients receiving l ‐asparaginase: two retrospective investigations (one on children and one on adult patients) [2,8] and three prospective studies on pediatric patients [4,9,10]. Recently, a retrospective investigation on a large series of patients focused the association between venous thromboembolism (VTE) and acute leukemia before starting chemotherapy [11].…”

Section: Introductionmentioning

confidence: 99%

The risk of thrombosis in patients with acute leukemia: occurrence of thrombosis at diagnosis and during treatment

Stefano¹,

Sorà²,

Rossi³

et al. 2005

Journal of Thrombosis and Haemostasis

225

165

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Summary. Background: Thromboembolism can occur during acute leukemia, especially acute lymphoid leukemia (ALL) treated with l‐asparaginase. Yet, most reports are anecdotical and scarce data are available on the risk of thrombosis in acute myeloid leukemia (AML). Objectives: To evaluate the risk of thrombosis in patients with acute leukemia. Patients and methods: Three‐hundred and seventy‐nine consecutive adult patients with newly diagnosed acute leukemia were recruited in an observational cohort study conducted from January 1994 to December 2003. Diagnosis was ALL in 69 patients, acute promyelocytic leukemia (APL; FAB subtype M3) in 31, and non‐M3 AML in 279. All first or recurrent symptomatic thromboembolic events objectively diagnosed were recorded. Results: Twenty‐four patients of the overall 379 (6.3%; 95% CI 4.1%–9.2%) had a first thrombosis, venous in 80% of the cases and arterial in 20%. At diagnosis, thrombosis was a presenting manifestation in 13 cases (3.4% of the whole cohort): 1.4% in ALL, 9.6% in APL, and 3.2% in non‐M3 AML patients. Follow‐up was carried out on 343 patients without thrombosis at diagnosis and further 11 thrombotic events (3.2%) were recorded. At 6 months from diagnosis, the cumulative incidence of thrombosis was 10.6% in ALL, 8.4% in APL, and 1.7% in non‐M3 AML patients. The patients who received l‐asparaginase had a 4.9‐fold increased risk of thrombosis in comparison with those who did not (95% CI 1.5–16.0). The fatality rate due to thrombosis was 0.8%. Conclusions: In patients with acute leukemia, the risk of thrombosis is not negligible. Thombosis can be a presenting symptom at diagnosis in a significant portion of cases with APL (9.6%) and non‐M3 AML (3.2%); a similar rate of thrombosis can occur during the subsequent course of the disease. The incidence of symptomatic thrombosis at diagnosis is relatively low in ALL patients (1.4%), but is significantly increased by further treatment up to 10.6%. Strategies of antithrombotic prophylaxis should be investigated in this setting.

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Low rate of severe venous thromboses in children with ALL treatment according to COALL-92 and -97 protocol

Cited by 10 publications

References 7 publications

Cerebral Sinus Occlusion in a Boy Presenting with Asparaginase-Induced Hypertriglyceridemia

Cerebral Sinus Occlusion in a Boy Presenting with Asparaginase-Induced Hypertriglyceridemia

Thrombosis and acute lymphoblastic leukaemia

The risk of thrombosis in patients with acute leukemia: occurrence of thrombosis at diagnosis and during treatment

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