Cerebral sinus venous thrombosis during childhood acute lymphoblastic leukemia therapy: Risk factors and management
Khaled GhanemRaghida M. DhayniCarol Al‐AridiNidale TarekHani TamimAnthony K.C. ChanRaya SaabMiguel R. AbboudHassan El‐SolhSamar Muwakkit
45
Citation
22
Reference
10
Related Paper
Citation Trend
Abstract:
Abstract Background Cerebral sinus venous thrombosis (CSVT) is a rare but serious complication of childhood acute lymphoblastic leukemia (ALL) therapy. No available consensus exists regarding its risk factors and appropriate management due to the rarity of cases. Procedures Out of 209 ALL patients aged 1–21 years treated at the Children's Cancer Center of Lebanon between May 2002 and May 2015, 13 developed CSVT during therapy. Patient characteristics, clinical management, and outcomes were studied. Results The incidence of CSVT was 6.2% (95% confidence interval [CI]: 3.4–10.4). Using univariate analysis, increased risk of CSVT was observed with age >10 years (odds ratio [OR]: 3.56, 95% CI: 1.13–11.2), T‐cell immunophenotype (OR: 4.14, 95% CI: 1.16–14.7), and intermediate/high risk disease (OR: 3.4, 95% CI: 1.03–11.7). The only statistically significant risk factor by multivariate analysis was the treatment as per the intermediate‐/high‐risk protocol (HR: 15.6, 95% CI: 1.43–171.3). Most cases (77%) occurred in the postinduction phases of treatment while receiving a combination of asparaginase and dexamethasone rather than prednisone. Treatment with low molecular weight heparin (LMWH) for a minimum of 3 months and until significant radiological improvement is observed resulted in 100% survival rate. All but one patient had complete neurological recovery. Conclusions CSVT is an important complication of childhood ALL therapy. Postinduction combined asparaginase and dexamethasone intensive treatment for intermediate‐/high‐risk patients was the most important risk factor. Treatment with LMWH for a minimum of 3 months, and until asparginase therapy is over, with major radiological improvement seems to be effective and feasible.Keywords:
Asparaginase
Univariate analysis
The British Journal of Haematology publishes original research papers in clinical, laboratory and experimental haematology. The Journal also features annotations, reviews, short reports, images in haematology and Letters to the Editor.
Asparaginase
Asparagine synthetase
Refractory (planetary science)
Cite
Citations (1)
Asparaginase
Acute lymphocytic leukemia
Cite
Citations (63)
Monitoring of anti-Xa activity (aXa) levels is not routinely required in patients receiving enoxaparine at prophylactic dosages, since aXa is supposed to stay below the manufacturer's recommended range in patients treated for venous thrombosis (0.5-1 IU/ml). In order to aXa in elderly subjects receiving prophylactic enoxaparin, 68 consecutive patients (mean age 82.5 +/- 10.7 years) hospitalized in a medical department receiving 4000 IU enoxaparin daily subcutaneously for the prevention of venous thromboembolic disease were studied. After the first injection of enoxaparin, the aXa of 57.4% patients was superior to 0.5 IU/ml while 69.4% had an aXa higher than 0.5 after 8.4 +/- 1.2 days. A negative relationship between aXa and body weight and a trend towards a positive correlation between aXa and age but not with creatinine clearance were noted. Our findings question the opportunity to monitor aXa in elderly patients receiving 4000 IU enoxaparin as antithrombotic prophylaxis.
Dose
Enoxaparin sodium
Cite
Citations (28)
The paper reviews air travel and venous thrombosis. The risk of venous thrombosis increases with distance flown. The mechanisms that cause thrombosis are unknown, but may be related to hypobaric hypoxia, i.e. reduced air pressure inside the aeroplane, stasis of the lower limbs, often referred to as economy class syndrome (ECS), and dehydration.Symptomless deep venous thrombosis may occur in 10% of healthy long-haul airline travellers over 50 years of age, and up to 4.5% of passengers under 50 at high risk of thrombosis. Wearing of elastic compression stockings during the flight is associated with reduced risk of deep venous thrombosis.Passengers should be encouraged to use the muscle-vein pump regularly, ensure adequate hydration, and in some cases wear elastic compression stockings. A majority of passengers will not need any thromboprophylaxis. Aspirin may have a protective role, but its efficacy in preventing venous thrombosis is much smaller than that of low molecular weight heparins. A high prophylactic dose of a low molecular weight heparin should be considered in passengers at high risk of thrombosis.
Compression stockings
Air travel
Venous stasis
Cite
Citations (4)
Cite
Citations (4)
PURPOSE: The CNS is an important sanctuary site in childhood acute lymphoblastic leukemia (ALL). CSF asparagine concentration reflects asparaginase systemic pharmacodynamics. We evaluated the time course of CSF asparagine depletion in children with ALL during and after a course of Escherichia coli asparaginase. PATIENTS AND METHODS: Thirty-one children (24 newly diagnosed and seven at relapse) received E coli asparaginase 10,000 IU/m 2 intramuscularly three times weekly for six and nine doses, respectively, as part of multiagent induction chemotherapy. CSF asparagine levels were measured before, during, and after asparaginase dosing. RESULTS: The percentage of patients with undetectable (< 0.04 μmol/L) CSF asparagine was 3.2% (one of 31 patients) at baseline, 73.9% (17 of 23) during asparaginase therapy, and 56.3% (nine of 16) 1 to 5 days, 43.8% (seven of 16) 6 to 10 days, 20.0% (two of 10) 11 to 30 days and 0% (zero of 21) more than 30 days after asparaginase therapy. The proportion of patients with depleted CSF asparagine was higher during asparaginase therapy than at baseline (P < .001), 11 to 30 days (P = .003), and more than 30 days after asparaginase therapy (P < .001). Median CSF asparagine concentrations were 4.42 μmol/L before, less than 0.04 μmol/L during, and less than 0.04 μmol/L at 1 to 5 days, 1.63 μmol/L at 6 to 10 days, 1.70 μmol/L at 11 to 30 days, and 5.70 μmol/L at more than 30 days after asparaginase therapy, respectively. CSF depletion was more common in patients with low baseline CSF asparagine concentrations (P = .003). CONCLUSION: CSF asparagine concentrations are depleted by conventional doses of E coli asparaginase in the majority of patients, but they rebound once asparaginase therapy is completed.
Asparaginase
Cite
Citations (44)
Hematology
Cite
Citations (12)
Pediatric Acute Lymphoblastic Leukemia (ALL) cure rates have improved exponentially over the past five decades with now over 90% of children achieving long-term survival. A direct contributor to this remarkable feat is the development and expanded understanding of combination chemotherapy. Asparaginase is the most recent addition to the ALL chemotherapy backbone and has now become a hallmark of therapy. It is generally accepted that the therapeutic effects of asparaginase is due to depletion of the essential amino acid asparagine, thus occupying a unique space within the therapeutic landscape of ALL. Pharmacokinetic and pharmacodynamic profiling have allowed a detailed and accessible insight into the biochemical effects of asparaginase resulting in regular clinical use of therapeutic drug monitoring (TDM). Asparaginase's derivation from bacteria, and in some cases conjugation with a polyethylene glycol (PEG) moiety, have contributed to a unique toxicity profile with hypersensitivity reactions being the most salient. Hypersensitivity, along with several other toxicities, has limited the use of asparaginase in some populations of ALL patients. Both TDM and toxicities have contributed to the variety of approaches to the incorporation of asparaginase into the treatment of ALL. Regardless of the approach to asparagine depletion, it has continually demonstrated to be among the most important components of ALL therapy. Despite regular use over the past 50 years, and its incorporation into the standard of care treatment for ALL, there remains much yet to be discovered and ample room for improvement within the utilization of asparaginase therapy.
Asparaginase
Lymphoblastic lymphoma
Acute lymphocytic leukemia
Cite
Citations (51)
Asparaginase
Acute lymphocytic leukemia
Cite
Citations (127)