Researchers have developed a microfluidic leukapheresis method aimed at safely and effectively reducing unprecedented blood leukocyte levels, particularly among pediatric patients suffering from hyperleukocytosis linked to acute leukemia. Conventional leukapheresis techniques, which typically rely on centrifugation, expose children to serious complications due to their large extracorporeal volumes and high flow rates. The new microfluidic approach may provide significant advantages, minimizing these risks.
Acute leukemia accounts for the highest incidence of cancer among children, with as many as 20-30% of these patients developing hyperleukocytosis, defined as having over 100,000 white blood cells (WBC) per microliter. Hyperleukocytosis can lead to life-threatening complications, prompting the need for effective intervention strategies like therapeutic leukapheresis. Traditionally performed using centrifugation, this procedure often involves significant blood loss and complications, especially for pediatric patients with limited blood volumes.
The innovative microfluidic devices utilize controlled incremental filtration (CIF), providing extra advantages over conventional methods. During testing, these devices achieved approximately 80% collection efficiency for larger leukocytes, significantly minimizing platelet losses compared to traditional procedures. Evaluations conducted on Sprague-Dawley rats illustrated not only the efficacy but also the safety of this approach, as no adverse effects were recorded compared to sham controls.
"Microfluidics-based leukapheresis is safe and effective at selectively removing leukocytes from circulation, with separation performance sufficiently high to enable low extracorporeal volume leukapheresis," remarked the researchers.
During experiments, multiplexed devices linked parallelly facilitated faster flow rates. Remarkably, when this device was connected to the rats, it was able to decrease circulating WBC counts by nearly half within three hours of the procedure, with no harmful impact on plasma biomarkers or end-organ function, indicating the method's tolerability.
Another notable finding was the substantially lower extracorporeal volume (ECV) of approximately 0.74 mL used during the procedures, which accounted for only 3% of the rats' estimated total blood volume (eTBV). This contrasts starkly with the much larger volumes needed for traditional centrifugation devices, which can exceed hundreds of milliliters.
The researchers emphasized the positive ramifications this technique could have, particularly aiming to enable therapeutic leukapheresis for pediatric patients who are currently restricted from undergoing such procedures due to their size and safety concerns. Leveraging the small footprint and low volume requirements of the microfluidic devices significantly reduces the need for sedation, invasive catheter placements, and potential complications like dilutional anemia.
"Our data suggest CIF-enabled microfluidic devices may be feasible alternatives to centrifugation-based leukapheresis, especially for the vulnerable pediatric population," the authors noted.
The implementation of this groundbreaking technology could lead to quicker and safer interventions for children facing acute leukemia, with the potential to minimize delays before beginning chemotherapy treatment. Future studies are anticipated to investigate the efficacy of this microfluidic leukapheresis approach in larger animal models before progressing to first-in-human trials.