Venous thrombosis in children, adolescents and young adults with acute lymphoblastic leukemia receiving chemotherapy in the Republic of Belarus

V V Dmitriev,E V Dmitriev,O I Bydanov,N V Lipay,N V Migal

doi:10.17650/1818-8346-2019-14-2-13-23

Abstract

Objective: to clarify the conditions for the occurrence of thrombosis and assess the effect of anticoagulant therapy on the survival and outcome of thrombosis in children, adolescents and young adults with acute lymphoblastic leukemia (ALL) receiving program chemotherapy.Materials and methods. The study included 592 patients with ALL received program chemotherapy from 2008 to 2017 in the Belarusian Research Center for Pediatric Oncology, Hematology and Immunology (Minsk, Belarus). Of them, in 42 patients various localization venous thrombosis was detected at different therapy phase.Results.The cumulative detection rate of thrombosis was 7.5 ± 1.1 %. The use of pegelated asparaginase (PEG-asp) at a dose of 1000 IU/m2 in induction therapy increased the relative risk of thrombosis in the first 5 weeks of treatment by 3 times (relative risk 3.4; 95 % confidence interval 0.98–11.9), compared to patients not receiving PEG-asp. The cumulative detection rate of thrombosis in patients with the post-induction L-asparaginase (L-asp) 25,000 IU/m2 regimen was 14.7 ± 2.6 %, which was higher (p = 0.0536) than when using L-asp in other dosing regimens. In addition to ALL as the main disease, taking chemotherapy drugs, other risk factors for thrombosis (thrombophilia, the presence of antiphospholipid antibodies, a decrease of natural anticoagulants activity) in various combinations were in half (23 of 42) patients with venous thrombosis. Therapeutic dose of low molecular weight heparins (LMWH) 150–200 IU/kg received 30 patients. Reduced for the period of thrombocytopenia from 100 to 35 × 109/L for up to 4 weeks, a daily dose of LMWH was received by 12 patients. The dose of LMWH was reduced in proportion to the blood platelets count. After the recovery of the platelet count of more than 100 × 109/L, patients continued treatment of LMWH in a daily dose of 150–200 anti-Xa IU/kg. Reducing of LMWH dose during thrombocytopenia period did not affect the outcome of thrombosis (χ2 = 0.494; p = 0.78). Among 42 patients with thrombosis, 38 completed maintenance therapy, eventfree survival was 83.0 ± 8.0%, which did not differ (p = 0.654) from that (81.0 ± 2.0 %) in patients without thrombosis. Conclusion. The presence of venous thrombosis with the use of LMWH as antithrombotic therapy did not lead to a decrease in the event-free survival of ALL patients, compared with those without thrombosis. Reducing the therapeutic dose of LMWH did not affect the outcome of thrombosis in the analyzed groups.

Highlights

Для цитирования: Дмитриев В.В., Мигаль Н.В., Быданов О.И. и др
In 42 patients various localization venous thrombosis was detected at different therapy phase
In addition to ALL as the main disease, taking chemotherapy drugs, other risk factors for thrombosis in various combinations were in half (23 of 42) patients with venous thrombosis

Summary

Характеристика Characteristic

12,9; 0,0003 справа – 6), глубоких вен правой руки – 1, бедренной вены – 2, бедренной вены с распространением до наружной подвздошной вены – 7 (слева – 3, справа – 4). Тромбоз венозных синусов выявлен методом магнитно-резонансной ангиографии у 8 пациентов в связи с прогрессированием общемозговой симптоматики: в первые 5 нед индукционной терапии – у 6 (2 детей и 4 молодых взрослых), с 6 по 12‐ю неделю – у 2 (1 ребенок и 1 молодой взрослый пациент). Во всех протоколах как на этапе индукционной терапии, так и на этапах консолидации использовали лекарственные средства, содержащие L-asp: Escherichia coli L-asp На протоколах кооперативной исследовательской группы по изучению ОЛЛ у детей и подростков использовали следующие комбинации: на этапе индукции – PEG-asp только на 3‐й день от начала терапии в дозе 1000 МЕ / м2 в течение 1 ч (у молодых взрослых обязательно) на фоне перорального приема дексаметазона в дозе 6 мг / м2 в течение 36 дней; на этапах консолидации – L-asp. На этапе индукционной терапии протокола ALL-MB-2015 PEG-asp является обязательным препаратом Distribution of patients according to acute lymphoblastic leukemia treatment protocols

Постиндукционный режим аспарагиназы Asparaginase in postinduction therapy

Случаи Кумулятивn тромбоза Cases ная частота Cumulative of thrombosis incidence

Findings

Этап консолидации Consolidation