Patients undergoing hematopoietic cell transplantation (HCT) face more than just the challenges of their disease — they also must withstand the rigors of intense treatment. But City of Hope researchers are pursuing a high-tech form of highly targeted radiation therapy that could ease treatment side effects and allow more patients to benefit from HCT. Their latest results appear in January issues of two major scientific journals, Clinical Cancer Research and Blood.
|Jeffrey Wong and a team of clinical researchers are studying total marrow irradiation for hematopoietic cell transplant patients. (Photo by p.cunningham)|
HCT aims to replace diseased cells in a patient’s bone marrow with healthy blood stem cells. But physicians first must use high-dose chemotherapy — with or without radiation therapy — to destroy the patient’s diseased marrow. When used, radiation therapy usually comes in the form of total body irradiation, or TBI, which can cause significant side effects.
City of Hope researchers are the first to explore total marrow irradiation, or TMI, as a replacement for TBI for transplant patients. TMI uses an advanced way to deliver radiation called TomoTherapy, which allows physicians to focus radiation beams on diseased bone marrow and avoid exposure to healthy tissues. The researchers hope this will lessen side affects while allowing for higher doses of therapeutic radiation.
In 2006, City of Hope was the first institution in the world to use TMI to treat patients battling multiple myeloma. This year, a team headed by lead author George Somlo, M.D., professor in the Department of Medical Oncology & Therapeutics Research and member of the Department of Hematology & Hematopoietic Cell Transplantation, and senior author Jeffrey Y.C. Wong, M.D., chair of the Department of Radiation Oncology, reported their promising findings in the Jan. 1 issue of Clinical Cancer Research. The journal featured the study on its cover.
|George Somlo (Photo by p.cunningham)|
Standard treatment for multiple myeloma includes some combination of high-dose chemotherapy followed by autologous HCT, a procedure in which patients receive their own blood stem cells to rebuild their blood and immune systems. Radiation therapy also may be used against multiple myeloma, but studies have shown that TBI is unacceptably toxic when given along with high-dose chemotherapy in these patients.
The City of Hope team investigated whether TMI could lessen or reduce side effects. In the phase I trial reported in the journal, 22 patients underwent high-dose chemotherapy followed by autologous HCT. About two months later, they underwent TMI and a second autologous HCT.
“Treatment-related side effects following TMI were less than expected despite radiation doses up to 1.5 times greater than possible for standard TBI treatment, and disease control was promising in comparison to standard therapy,” said Somlo.
The team launched a phase II clinical trial to further test the strategy. Physicians hope that TMI after high-dose chemotherapy will help kill myeloma stem cells — immature cells believed to give rise to cancer — that often survive less intense treatment.
“Cancer stem cells are likely a major reason for relapse in patients with multiple myeloma,” said Somlo. “In our pursuit to cure, we’re looking for any advantage we can find.”
Some patients, like young children and older adults, cannot tolerate intense treatments, so physicians must try other treatment options. In the January issue of Blood, City of Hope researchers reported results of a study testing a technique called total marrow and lymph node irradiation as a form of reduced-intensity conditioning before transplantation.
Reduced-intensity conditioning uses lower doses of chemotherapy and radiation to knock out patients’ diseased bone marrow before they undergo allogeneic HCT, a transplant using stem cells from a donor.
“For many hematologic cancers, transplant is simply the best treatment option. Reduced-intensity conditioning allows more patients to receive the benefits of transplantation,” said Joseph Rosenthal, M.D., director of the Pediatric HCT Program, who co-led the study with Wong.
The new technique targets higher doses of radiation specifically to bone marrow and lymph nodes. Rosenthal and Wong found that patients in their study tolerated the new technique as well as those undergoing standard reduced-intensity conditioning. The team now is designing studies to test if the technique improves outcomes.
Expanding the use of HCT
Initial patient responses are encouraging, Wong said. “By reducing side effects, we have been able to successfully perform TMI-based transplants in patients who would not have tolerated a standard transplant procedure,” Wong said.
This is an important step since many patients with blood cancers such as multiple myeloma and acute myelogenous leukemia are unable to tolerate more-intense therapy due to advanced age, Wong said.
“Reduction in side effects has also allowed for the selective targeting of more therapeutic radiation to the marrow that harbors the greatest burden of malignant cells,” he said. “Now we can design larger studies to see if patients receive additional benefit from TMI.”
Team efforts lead to concurrent publications
Two studies exploring total marrow irradiation were published in January issues of the journals Clinical Cancer Research and Blood.
Authors on the studies included:
- Department of Radiation Oncology — An Liu, Ph.D., Timothy Schultheiss, Ph.D., and Jeffrey Y.C. Wong, M.D.
- Department of Hematology & Hematopoietic Cell Transplantation — Stephen J. Forman, M.D., Chatchada Karanes, M.D., Neil M. Kogut, M.D., Amrita Y. Krishnan, M.D., Pablo M. Parker, M.D., Leslie L. Popplewell, M.D., Firoozeh Sahebi, M.D., David S. Snyder, M.D., George Somlo, M.D. (also part of the Department of Medical Oncology & Therapeutics Research), Ricardo Spielberger, M.D., Anthony S. Stein, M.D., and Sandra H. Thomas
- Department of Pediatrics — Joseph Rosenthal, M.D., and Debbie Hitt, R.N.
- Department of Information Sciences — Andrew Dagis, Ph.D., Paul Frankel, Ph.D., Hossameldin Naeem and Dajun Qian, Ph.D.
The National Cancer Institute supported both studies.