M K Mateos1, T N Trahair2, C Mayoh3, P M Barbaro4, R Sutton5, T Revesz6, D Barbaric7, J E Giles3, F Alvaro8, F Mechinaud9, D Catchpoole10, R S Kotecha11, L Dalla-Pozza12, M C J Quinn13, S MacGregor13, G Chenevix-Trench14, G M Marshall2. 1. Kids Cancer Centre, Sydney Children's Hospital, Randwick, NSW, Australia; Children's Cancer Institute, Lowy Cancer Centre, UNSW, NSW, Australia; School of Women's & Children's Health, UNSW, NSW, Australia. Electronic address: m.mateos@unsw.edu.au. 2. Kids Cancer Centre, Sydney Children's Hospital, Randwick, NSW, Australia; Children's Cancer Institute, Lowy Cancer Centre, UNSW, NSW, Australia; School of Women's & Children's Health, UNSW, NSW, Australia. 3. Children's Cancer Institute, Lowy Cancer Centre, UNSW, NSW, Australia. 4. Children's Medical Research Institute, Westmead, NSW, Australia; Department of Haematology, Lady Cilento Children's Hospital, Brisbane, Australia. 5. Children's Cancer Institute, Lowy Cancer Centre, UNSW, NSW, Australia; School of Women's & Children's Health, UNSW, NSW, Australia. 6. SA Pathology, Women's and Children's Hospital, North Adelaide, SA, Australia. 7. Kids Cancer Centre, Sydney Children's Hospital, Randwick, NSW, Australia. 8. Children's Cancer & Haematology Service, John Hunter Children's Hospital, New Lambton Heights, NSW, Australia. 9. Children's Cancer Centre, Royal Children's Hospital Melbourne, Parkville, VIC, Australia. 10. Children's Cancer Research Unit, The Children's Hospital at Westmead, Westmead, NSW, Australia. 11. Perth Children's Hospital, Perth, WA, Australia; Telethon Kids Cancer Centre, Telethon Kids Institute, University of Western Australia, Perth, WA, Australia; School of Pharmacy and Biomedical Sciences, Curtin University, Perth, WA, Australia. 12. Children's Cancer Research Unit, The Children's Hospital at Westmead, Westmead, NSW, Australia; Cancer Centre for Children, The Children's Hospital at Westmead, Westmead, NSW, Australia. 13. Statistical Genetics, QIMR Berghofer Medical Research Institute, Herston, QLD, Australia. 14. Cancer Genetics, QIMR Berghofer Medical Research Institute, Herston, QLD, Australia.
Abstract
BACKGROUND: Symptomatic venous thromboembolism (VTE) is an unpredictable and life-threatening toxicity, which occurs early in childhood acute lymphoblastic leukemia (ALL) therapy. Approximately 5% of children will experience VTE which is treated with anticoagulation. Asparaginase and corticosteroids are etiologic factors for VTE, however other clinical factors may modify this risk. PROCEDURE: We sought to i) assess published pre-treatment VTE risk factors ii) identify early clinical factors that were associated with VTE and iii) determine whether single nucleotide polymorphisms (SNPs) associated with VTE in non-cancer patients contributed to VTE in children with ALL. We performed a detailed, retrospective analysis of 1021 ALL patients treated between 1998 and 2013. Individual patient records were reviewed to ascertain VTE incidence and document treatment-related clinical variables. RESULTS: The incidence of VTE was 5.1%. Extremes of weight at diagnosis (<5th or >95th centile) was an independent risk factor in multivariable analysis, when added to published risk factors of age ≥10 years and mediastinal mass. When factors during induction/consolidation were considered separately: bacteremia, elevated serum gamma-glutamyl transferase and bilirubin were associated with VTE occurrence. None of the SNPs associated with VTE in non-cancer populations were significantly associated with VTE in our cohort. CONCLUSION: We found two known risk factors (age ≥ 10 years and mediastinal mass) in a large cohort of children treated for ALL and identified other factors associated with VTE such as weight extremes at diagnosis, bacteremia, and abnormal liver function which warrant further study. These VTE risk factors may form the basis of future thromboprophylaxis trials. Crown
BACKGROUND: Symptomatic venous thromboembolism (VTE) is an unpredictable and life-threatening toxicity, which occurs early in childhood acute lymphoblastic leukemia (ALL) therapy. Approximately 5% of children will experience VTE which is treated with anticoagulation. Asparaginase and corticosteroids are etiologic factors for VTE, however other clinical factors may modify this risk. PROCEDURE: We sought to i) assess published pre-treatment VTE risk factors ii) identify early clinical factors that were associated with VTE and iii) determine whether single nucleotide polymorphisms (SNPs) associated with VTE in non-cancerpatients contributed to VTE in children with ALL. We performed a detailed, retrospective analysis of 1021 ALL patients treated between 1998 and 2013. Individual patient records were reviewed to ascertain VTE incidence and document treatment-related clinical variables. RESULTS: The incidence of VTE was 5.1%. Extremes of weight at diagnosis (<5th or >95th centile) was an independent risk factor in multivariable analysis, when added to published risk factors of age ≥10 years and mediastinal mass. When factors during induction/consolidation were considered separately: bacteremia, elevated serum gamma-glutamyl transferase and bilirubin were associated with VTE occurrence. None of the SNPs associated with VTE in non-cancer populations were significantly associated with VTE in our cohort. CONCLUSION: We found two known risk factors (age ≥ 10 years and mediastinal mass) in a large cohort of children treated for ALL and identified other factors associated with VTE such as weight extremes at diagnosis, bacteremia, and abnormal liver function which warrant further study. These VTE risk factors may form the basis of future thromboprophylaxis trials. Crown
Authors: Marion K Mateos; Morten Tulstrup; Michael Cj Quinn; Ruta Tuckuviene; Glenn M Marshall; Ramneek Gupta; Chelsea Mayoh; Benjamin O Wolthers; Pasquale M Barbaro; Ellen Ruud; Rosemary Sutton; Pasi Huttunen; Tamas Revesz; Sonata S Trakymiene; Draga Barbaric; Ulf Tedgård; Jodie E Giles; Frank Alvaro; Olafur G Jonsson; Françoise Mechinaud; Kadri Saks; Daniel Catchpoole; Rishi S Kotecha; Luciano Dalla-Pozza; Georgia Chenevix-Trench; Toby N Trahair; Stuart MacGregor; Kjeld Schmiegelow Journal: Cancers (Basel) Date: 2020-05-19 Impact factor: 6.639
Authors: Laila M Sherief; Marwa Zakaria; Basma K Soliman; Naglaa M Kamal; Sultan A Alharthi; Sara As Abosabie; Mahmoud Abdelazeem Journal: SAGE Open Med Case Rep Date: 2022-08-12
Authors: Clarissa E Schilstra; Karen McCleary; Joanna E Fardell; Mark W Donoghoe; Emma McCormack; Rishi S Kotecha; Richard De Abreu Lourenco; Shanti Ramachandran; Ruelleyn Cockcroft; Rachel Conyers; Siobhan Cross; Luciano Dalla-Pozza; Peter Downie; Tamas Revesz; Michael Osborn; Frank Alvaro; Claire E Wakefield; Glenn M Marshall; Marion K Mateos; Toby N Trahair Journal: BMC Cancer Date: 2022-09-15 Impact factor: 4.638
Authors: Marion K Mateos; Glenn M Marshall; Pasquale M Barbaro; Michael C J Quinn; Carly George; Chelsea Mayoh; Rosemary Sutton; Tamas Revesz; Jodie E Giles; Draga Barbaric; Frank Alvaro; Françoise Mechinaud; Daniel Catchpoole; John A Lawson; Georgia Chenevix-Trench; Stuart MacGregor; Rishi S Kotecha; Luciano Dalla-Pozza; Toby N Trahair Journal: Haematologica Date: 2022-03-01 Impact factor: 9.941