Acute Lymphoblastic Leukaemias (ALL), Long Term Follow-Up
Conditions
Brief summary
With increasing survival rates in pediatric oncology, reports of long-term side effects persisting decades after treatment are also rising. Clinically evident nephropathies occur in about 5.5% of survivors more than five years after therapy. Chemotherapeutic agents such as ifosfamide, cisplatin, and carboplatin, as well as kidney-directed treatments like radiation, surgery, or stem cell transplantation, increase this risk. Acute kidney injury has also been described in association with cyclophosphamide and high-dose methotrexate, which are used in the treatment of acute lymphoblastic leukemia (ALL). Studies show a high prevalence of albuminuria (around 14.5% of childhood cancer survivors), an early marker of kidney damage, while standard parameters like creatinine often become abnormal only at later stages. Leukemia survivors suffer from vascular late effects caused by persistent endothelial damage triggered by cancer therapies such as anthracyclines, cyclophosphamide, and asparaginase, which increase inflammation and thrombosis risk. These vascular changes may also contribute to kidney injury. ULM is a high-resolution ultrasound technique that uses microbubbles to visualize the microvasculature and resolve dynamic blood flow changes with a resolution beyond the diffraction limit. ULM is independent of kidney or liver function, has been applied in various organs, and was recently used for the first time to visualize glomeruli-the smallest functional units of the kidney-in humans. This method enables early detection of glomerular injury as a consequence of vascular damage, even before albuminuria appears, potentially allowing earlier adaptation of follow-up and initiation of treatment. This pilot project focuses on survivors of ALL, as they are the largest and best studied pediatric cancer patient group also regarding late effects and, therefore, a sufficient number of individuals can be expected for his monocentric approach. Vascular functional impairment of the kidney could be detected at an early stage and the follow-up structures and measures such as the early use of nephroprotective drugs could be adapted.
Interventions
DIAGNOSTIC_TESTUltrasound Localization Microscopy (ULM)
Single Examination: ULM of the kidney after application of a contrast medium (SonoVue®, intravenous).
DIAGNOSTIC_TESTBlood sample
Blood draw (including BB, Diff, Glucose, Na, K, Cl, Ca, LDH, Crea, Cystatin C, Uric Acid, CRP, Albumin, Ferritin, Total Protein) through venous access.
DIAGNOSTIC_TESTUrinanalysis
Examination of urine for erythrocytes, leukocytes, pH value, nitrite, protein, blood, and electrolytes.
DIAGNOSTIC_TESTRenal sonography
Renal sonography including resistance index (RI), Doppler signal, flow velocity, and others.
Sponsors
University of Erlangen-Nürnberg Medical School
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
DIAGNOSTIC
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
3 Years to 17 Years
Healthy volunteers
No
Inclusion criteria
* Diagnosed acute lymphatic leukemia * From 3 years to \< 18 years * completed oncological treatment or treatment day \< 50 according to therapy protocol and no administration of CPM before first examination.
Exclusion criteria
* Known allergic disposition to SonoVue / other contrast agents * Tattoo in the area of the examination field * Pregnancy * Breastfeeding mothers * Contraindication for the use of Sonovue * Critical condition * Known clinically evident renal impairment
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| CEUS Measurement 12 | Study arm early therapeutic effects: Baseline before day 50 of the therapy and follow up after completion of intensive chemotherapy Study arm late therapeutic effects: Baseline at a single-time point in oncological follow-up care | Peak enhancement (PE) |
| CEUS Measurement 3 | Study arm early therapeutic effects: Baseline before day 50 of the therapy and follow up after completion of intensive chemotherapy Study arm late therapeutic effects: Baseline at a single-time point in oncological follow-up care | Wash-in perfusion index (WiPI) |
| CEUS Measurement 4 | Study arm early therapeutic effects: Baseline before day 50 of the therapy and follow up after completion of intensive chemotherapy Study arm late therapeutic effects: Baseline at a single-time point in oncological follow-up care | Wash-in rate (WIR) |
| CEUS Measurement 5 | Study arm early therapeutic effects: Baseline before day 50 of the therapy and follow up after completion of intensive chemotherapy Study arm late therapeutic effects: Baseline at a single-time point in oncological follow-up care | Wash-out under the curve (WoAUC) |
| CEUS Measurement 6 | Study arm early therapeutic effects: Baseline before day 50 of the therapy and follow up after completion of intensive chemotherapy Study arm late therapeutic effects: Baseline at a single-time point in oncological follow-up care | Wash-in and wash-out under the curve (WiWoAUC) |
| CEUS Measurement 7 | Study arm early therapeutic effects: Baseline before day 50 of the therapy and follow up after completion of intensive chemotherapy Study arm late therapeutic effects: Baseline at a single-time point in oncological follow-up care | Wash-out rate (WoR) |
| CEUS Measurement 8 | Study arm early therapeutic effects: Baseline before day 50 of the therapy and follow up after completion of intensive chemotherapy Study arm late therapeutic effects: Baseline at a single-time point in oncological follow-up care | Time to peak (TTP) |
| CEUS Measurement 9 | Study arm early therapeutic effects: Baseline before day 50 of the therapy and follow up after completion of intensive chemotherapy Study arm late therapeutic effects: Baseline at a single-time point in oncological follow-up care | Rise time (RT) |
| CEUS Measurement 10 | Study arm early therapeutic effects: Baseline before day 50 of the therapy and follow up after completion of intensive chemotherapy Study arm late therapeutic effects: Baseline at a single-time point in oncological follow-up care | Mean transit time (local) (mTTI) |
| CEUS Measurement 11 | Study arm early therapeutic effects: Baseline before day 50 of the therapy and follow up after completion of intensive chemotherapy Study arm late therapeutic effects: Baseline at a single-time point in oncological follow-up care | Fall time (FT) |
| CEUS Measurement 1 | Study arm early therapeutic effects: Baseline before day 50 of the therapy and follow up after completion of intensive chemotherapy Study arm late therapeutic effects: Baseline at a single-time point in oncological follow-up care | Peak enhancement (PE) |
| CEUS Measurement 2 | Study arm early therapeutic effects: Baseline before day 50 of the therapy and follow up after completion of intensive chemotherapy Study arm late therapeutic effects: Baseline at a single-time point in oncological follow-up care | Wash-in area under the curve (WIAUC) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Urine status | Study arm early therapeutic effects: Baseline before day 50 of the therapy and follow up after completion of intensive chemotherapy Study arm late therapeutic effects: Baseline at a single-time point in oncological follow-up care | Measurement of proteinuria in mg/l with protein differentiation |
| RI | Measurement of proteinuria with protein differentiation | Resistance index (Sonography) |
| Flow velocity | Study arm early therapeutic effects: Baseline before day 50 of the therapy and follow up after completion of intensive chemotherapy Study arm late therapeutic effects: Baseline at a single-time point in oncological follow-up care | Flow velocity in Doppler Signal (Sonography) |
| Weigth | Study arm early therapeutic effects: Baseline before day 50 of the therapy and follow up after completion of intensive chemotherapy Study arm late therapeutic effects: Baseline at a single-time point in oncological follow-up care | Weigth of the participant in kilograms |
| Height | Study arm early therapeutic effects: Baseline before day 50 of the therapy and follow up after completion of intensive chemotherapy Study arm late therapeutic effects: Baseline at a single-time point in oncological follow-up care | Height of the participant in meters |
| BP | Study arm early therapeutic effects: Baseline before day 50 of the therapy and follow up after completion of intensive chemotherapy Study arm late therapeutic effects: Baseline at a single-time point in oncological follow-up care | Measurement of systolic, diastolic and mean blood pressure in mmHg |
| Electrolytes | Study arm early therapeutic effects: Baseline before day 50 of the therapy and follow up after completion of intensive chemotherapy Study arm late therapeutic effects: Baseline at a single-time point in oncological follow-up care | Concentration of serum electrolytes (Na, K, Cl, Mg, P) in mmol/L. |
| Creatinin and urea level | Study arm early therapeutic effects: Baseline before day 50 of the therapy and follow up after completion of intensive chemotherapy Study arm late therapeutic effects: Baseline at a single-time point in oncological follow-up care | Serum Creatinin and urea level in mg/dl |
| Blood Count | Study arm early therapeutic effects: Baseline before day 50 of the therapy and follow up after completion of intensive chemotherapy Study arm late therapeutic effects: Baseline at a single-time point in oncological follow-up care | Complete blood count with number of red and white blood cells and platelets per µl |
Countries
Germany
Contacts
Primary ContactAxel Karow, MD
Backup ContactAlexander Dierl, MD
Outcome results
None listed