City of Hope radiation oncologists recently completed the world’s first total marrow and lymphoid irradiation treatment (TMLI) using TomoTherapy.

Through a pilot trial available only at City of Hope, a patient with acute myelogenous leukemia received customized, highly focused radiation therapy as part of the conditioning regimen for an allogeneic hematopoietic cell transplant.

The TomoTherapy Hi-Art system allowed radiation oncologists to target radiation beams specifically to bone marrow, lymph nodes and the spleen while limiting radiation exposure to the rest of the body. In contrast, traditional radiation therapy used in conditioning regimens — called total body irradiation, or TBI — exposes every part of the body to the energy beams.

Radiation therapy is meant to destroy any remaining cancer cells and suppress the immune system to accept new, transplanted hematopoietic cells.

“It’s too early to tell if this will replace total body irradiation,” said Jeffrey Wong, M.D., chair of the Division of Radiation Oncology. “But we feel this may be an appropriate way to administer radiation therapy to those who might not stand up to the rigor of TBI.”

Wong is an investigator in the phase 1 trial, which is led by principal investigator Joseph Rosenthal, M.D., director of the Department of Pediatric Hematopoietic Cell Transplantation. The first patient received TMLI in early August.

“We hope that this combination of chemotherapy and TMLI may result in fewer side effects, especially among children, who often have serious long-term effects from bone marrow transplantation,” said Rosenthal. “At the same time, we want to reduce the risk of their leukemia returning.”

Hematopoietic cell transplantation begins with a conditioning regimen, in which chemotherapy is used — with or without radiation therapy — to kill many of the cancerous cells riddling the body. After finishing the regimen, patients receive infusions of replacement hematopoietic (blood) stem cells, either from the patients themselves (called autologous transplants) or from matched donors (allogeneic transplants). These new cells give rise to the patient’s new immune system.

As Wong explained, today’s TBI requires patients to stand up while a machine administers radiation from head to toe. Patients receive radiation three times a day over four days, resulting in 10 to 11 treatments. The radiation exposure may cause side effects such as sore throat, fatigue, nausea, vomiting and diarrhea.

But the new investigational therapy requires only eight treatments — with doses given twice a day for four days — and patients undergo treatment lying down. At the same time, patients receive two chemotherapy drugs believed to be more tolerable than other similar medications.

Wong and colleagues hope the combination of focused radiation and milder chemotherapy will make treatment easier for children and patients over age 55, both vulnerable groups. “With TomoTherapy, the radiation dose to normal tissues is substantially reduced, which we believe may reduce side effects,” he said. 

Researchers hope to open another trial soon, with Anthony Stein, M.D., as principal investigator, evaluating a more intensive treatment regimen for younger adult patients with acute myelogenous leukemia.

Wong said City of Hope is the first to evaluate TMLI because it was one of the first centers to acquire and use TomoTherapy. “We worked with TomoTherapy to develop the concept before we even acquired the machine,” Wong said. “In addition, we have a large bone marrow transplant program — and a strong track record with clinical trials.”