Acute Lymphoblastic Leukemia, Bleeding, Hemostatic Disorder, Thrombosis
Conditions
Brief summary
The goal of this study is to investigate the hemostatic balance in children with acute lymphoblastic leukaemia (ALL) treated according to the ALLTogether1 protocol with focus on the early treatment period including concomitant use of steroids and asparaginase. The investigators aim to determine if complement proteins or microparticles can be used as clinically relevant predictive or diagnostic biomarkers for thrombosis and if global hemostatic assays can predict bleeding or thrombosis. Characterization of proteins connected to hemostasis before and during ALL treatment may provide pathophysiological insights regarding ALL- and treatment related coagulopathy. The ultimate goal of the study is to minimize the morbidity and mortality related to thrombosis and bleeding complications in children with ALL. Several pediatric oncology centers in Sweden will be participating in this study, which will enroll approximately 100 pediatric patients.
Interventions
DIAGNOSTIC_TESTCoagulopathy parameters
Standard coagulation tests: APT (Activated Partial Thromboplastin Time), PT/INR (Prothrombin Time Test), Protein-C, Protein-S, Fibrinogen, Antithrombin, D-dimers. Global haemostasis assays: CAT (Calibrated Automated Thrombogram), OHP (Overall Haemostatic Potential), Fibrin clot turbidity assay, microparticle detection by flow cytometry, scanning electron microscopy. Protein expression profile (mass spectroscopy) Ultrasound of catheterised neck veins to detect clots
Sponsors
Karolinska Institutet
Karolinska University Hospital
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
1 Years to 17 Years
Healthy volunteers
No
Inclusion criteria
* Diagnosis of Acute Lymphoblastic Leukaemia (ALL) in Sweden * Age 1-17.99 years at diagnosis * Planned/Initiated treatment for ALL according to the ALLTogether1 protocol * Signed informed consent from parents and patients (from 12 years - voluntary if \<15 years)
Exclusion criteria
* Other underlying diseases which according to examiner's clinical assessment may increase the risk of bleeding or thrombosis and which are expected to lead to adaption of the therapy protocol for ALL (e g APS, moderate/severe v Willebrand disease, haemophilia) * Patient not treated according to the ALLTogether1 protocol (including patients with BCR::ABL1, mixed phenotype acute leukaemia - MPAL)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Coagulation events (thrombosis and/or bleeding) in early phases of treatment for childhood ALL according to the ALLTogether1 therapy protocol | From diagnosis until the start of the subsequent phase of therapy (day 0 to 106 in protocol therapy) | Incidence of coagulation events during the induction and consolidation phases (first 106 days of ALL-therapy) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Laboratory abnormalities indicating a risk of haemostatic events in the early phases of childhood ALL therapy | From diagnosis until the start of the subsequent phase of therapy (day 0 to 106 in protocol therapy) | Incidence of laboratory abnormalities during the induction and consolidation phases (first 106 days of ALL-therapy) |
| Sub-clinical catheter-related thrombosis (central vein catheters) during the early phases of childhood ALL therapy | At the end of induction (protocol day 29 +/- 3 days) | Thrombosis detected by ultrasound screening of catheterised neck veins |
Contacts
Primary ContactMats M Heyman, M.D., PhD
Backup ContactLovisa H Malmqvist, M.D.
Outcome results
None listed