For the past decade, Children’s Mercy Hospital and Clinics’ Jignesh Dalal, MD, has worked to perfect a widely used therapy that reduces bone marrow rejection, making it safe for children.
Within the past year, supported by a $120,000 grant from the Midwest Cancer Alliance, Dr. Dalal and his colleagues have designed photopheresis for pediatric patients for treatment of graft-versus-host disease. To date, they have completed this therapy in many patients, demonstrating photopheresis can be tolerated in children.
“We’ve shown we can successfully do this in children,” says Dr. Dalal, Chief of Bone Marrow Transplantation Section. “Taking blood out of a child’s body can be dangerous. But we’ve done it and alleviated the difficult side effects that come with a bone marrow transplant.”
After mixing a bowl of blood with psoralen, they expose cells to ultraviolet light, killing reactive lymphocytes. Then, they infuse the blood back in to help generate tolerance. The machine designed for children uses a smaller bowl and circuit size, decreasing the time blood is outside the body.
After the procedure, Dr. Dalal and his colleagues monitor patients very closely. For two months post-transplant, they check in with patients twice a week. The frequency falls to twice every 15 days for the following six months.
During this time, our research team monitors B-cells and T-cells at two-month, four-month and six-month intervals. Doing so helps them determine how the body generates tolerance and which immune system cells play the biggest roles in the process. If the cells are imbalanced, putting a child at risk for graft-versus-host disease, the team attempts to push them back into equilibrium.
So far, Dr. Dalal says, the results have been very encouraging.
Of the nine patients currently enrolled in the study, five have completed the photopheresis therapy. According to Dr. Dalal, between 50% and 60% of patients experience positive benefits, including increased energy, skin loosening, decreased eye and mouth dryness, and an overall improved quality of life.
“We’re seeing the positive effect of the photopheresis appear between four to six weeks after transplant, and the peak benefit comes at around four to six months,” Dr. Dalal says. “From what we’ve seen, that positive effect remains.”
Understanding how cells generate tolerance has broader-reaching implications. With this knowledge our team could ultimately reduce rejection rates for solid organ transplants or improve treatments for lupus and scleroderma.
The result of our team’s work is a significant step forward. Successful photopheresis eliminates the need for immune-suppressive drugs, making children less vulnerable to viral, fungal or bacterial infections that can attack their comprised immune systems.
In addition, the team is currently analyzing data for its next challenge – understanding the chemotherapy drug cyclophosphamide.
“This drug isn’t well understood. Currently, we give all patients the same dosage,” Dr. Dalal says. “At Children’s Mercy Hospital, we’re investigating whether genes play a role in how the body metabolizes it and if different doses produce different side effects and desirable effects.”
This continued research strengthens Children’s Mercy’s existing reputation as a world-class pediatric cancer facility bringing cutting-edge therapies to patients.