Researchers at the University of Houston, in collaboration with Baylor College of Medicine, are developing new devices for treating children with hyperleukocytosis, a condition that develops when the body has an extremely high number of white blood cells, often due to leukemia.

Leukemia is the most common type of cancer in children, with an annual incidence of about 5 per 100,000 children in the United States. Up to 20–30% of patients with acute leukemia develop hyperleukocytosis, placing them at risk for life-threatening complications.

Although definitive treatment for acute leukemia involves chemotherapy, leukapheresis—to urgently reduce dangerously elevated white blood cell counts—is a potentially life-saving therapeutic option. During leukapheresis, a large machine uses centrifugation to separate white blood cells, or leukocytes, from the rest of the blood, which is then returned to the patient.

But for children, these conventional blood-filtering machines can be dangerous for several reasons.

Dangers for children include:

• High Extracorporeal volume or ECV—This refers to the amount of blood that is outside the body during a medical procedure. Since children have much less blood than adults, removing too much at once can make them weak or cause serious problems.
• High flow rates—The machine moves blood very quickly through the system which can be risky because it requires the use of large-bore central catheters and puts stress on the body, especially for children who have smaller blood volumes.
• Loss of platelets—Losing too many platelets can make it harder for blood to clot, increasing the risk of bleeding.

Finding another way

On one particularly difficult night in the intensive care unit, Dr. Fong Lam, an associate professor of pediatrics at Baylor College of Medicine and a pediatric intensive care physician at Texas Children’s Hospital, thought, “There has to be a better way.”

It was a night he had no choice but to perform leukapheresis on a young infant with leukemia. “The ECV of the apheresis machine is nearly as large as the child’s total blood volume,” he remembers thinking.

Lam partnered with Sergey Shevkoplyas, a professor of biomedical engineering at UH, to test whether performing cell separation with a high-throughput microfluidic device could alleviate these limitations. The results of their groundbreaking study, led by Mubasher Iqbal, a Ph.D. candidate in biomedical engineering at UH, appear in the journal Nature Communications.

A new way forward

The new microfluidic device uses a large number of tiny channels, about the width of a human hair, designed to quickly and efficiently separate blood cells by size in a process called controlled incremental filtration.

“In vitro, our microfluidic devices removed ~85% of large leukocytes and ~90% of spiked leukemic blasts from undiluted human whole blood,” reports Shevkoplyas. Leukemic blasts are cancerous white blood cells that don’t develop properly. Instead of growing into healthy cells that help fight infections, they multiply too fast and crowd out normal blood cells.

When tested in vivo, the device demonstrated a similar leukocyte collection efficiency without platelet loss or any other adverse effects, while recirculating undiluted whole blood for more than three hours, a typical duration of a leukapheresis procedure.

“Continuously and efficiently separating leukocytes from recirculating undiluted whole blood—without device clogging and cell activation or damage—has long been a major challenge in microfluidic cell separation,” Shevkoplyas said. “Our study is the first to solve this problem.”

“As a practicing physician, I was particularly excited that our multiplexed device could operate at clinically relevant flow rates but with ECV ~1/70th of the typical leukapheresis circuit. Such a dramatic reduction of ECV would be particularly important in leukemic infants with hyperleukocytosis who are often too small on which to perform centrifugation-based leukapheresis safely,” said Lam.

“Overall, our study suggests that microfluidics leukapheresis is safe and effective at selectively removing leukocytes from circulation, with separation performance sufficiently high to ultimately enable safe leukapheresis in children,” said Shevkoplyas.