New-Style Stem Cell Transplants Offer Hope to Blood Cancer Patients
For blood cancer patients, cures require killing nearly every cancer cell without harming non-cancerous tissues. This is a tough goal, but new therapies are on the horizon, including "targeted" treatments and better stem cell transplants.
I will discuss targeted therapy more fully in an upcoming Links. Suffice to say that targeted treatments hold great promise and are less toxic than standard anti-cancer drugs. As for their effectiveness, they are potentially very exciting, but researchers are still determining whether they can kill enough cancer cells to provide long-term cures.
Stem cell transplants, however, have a proven curative record and remain the best option for many blood cancer patients. Unfortunately, they also come with substantial risks. Before a patient undergoes a conventional stem cell transplant, doctors must use high-dose radiation and/or chemotherapy to efficiently kill cancer cells. But most blood cancer patients are over the age of 50, and older patients are often unable to withstand the toxicity of standard transplant regimens. The same holds true for younger people with certain health issues. This vulnerable population is more likely to succumb to high-dose treatment or develop life-threatening graft-versus-host disease, which is caused by transplanted immune cells attacking a patient's normal cells.
Now, new experimental transplants using lower chemotherapy or radiation doses and/or more cancer-specific treatments are being introduced around the world. They have the potential to increase the safety of stem cell transplants and improve overall survival.
One new technique is the use of radioimmunotherapy, in which antibodies are used to deliver radiation directly to tumor cells before a transplant, eliminating the need for high-dose, whole-body chemotherapy or radiotherapy. A Society-funded Specialized Center of Research (SCOR) team led by Irwin Bernstein, M.D., of Fred Hutchinson Cancer Research Center, is studying this approach and reported its most recent findings at the annual American Society of Hematology (ASH) conference in December.
SCOR member John Pagel, M.D. described results from a phase I clinical trial that has used a radioactive antibody (anti-CD45) as part of a reduced-intensity transplant procedure to treat 33 older (50-plus years of age) patients with advanced acute myeloid leukemia (AML) or high-risk myelodysplastic syndrome. High doses of killing radiation have been specifically targeted by the antibody to cancer sites, including bone marrow and spleen, without markedly increasing toxicities. This dose-escalation study is still underway at the Seattle Cancer Care Alliance.
Dr. Pagel and his colleagues have already shown that this same antibody can measurably increase the curative power of conventional chemotherapy/transplant treatments for young adult AML patients in first remission. A follow-up trial is about to open at multiple clinical research centers around the country. Specifics, including entry criteria, will soon be available at www.seattlecca.org.
Ajay Gopal, M.D., another SCOR team researcher, presented results of a phase II clinical trial using another radioactive antibody (anti-CD20, tositumomab, GlaxoSmithKline) to provide tumor-targeted radiation in elderly patients (60 plus years of age) with advanced, non-Hodgkin lymphoma unresponsive to conventional chemotherapy. Transplants were performed using the patient's own healthy stem cells after cancer cells were removed. Findings for the first 24 patients suggest that radioactive antibodies will also help older lymphoma patients undergoing stem cell transplants. The study is still open.
While larger studies with longer follow-up are needed to confirm that radioimmunotherapy can improve overall survival, results so far suggest that blood cancer patients, including those who are not candidates for standard transplants, will indeed benefit from this new procedure. Visit www.clinicaltrials.gov for a list of clinical trials that are testing radioimmunotherapy.
Clearly, less toxic treatments mean less hospitalization, so both survivorship and quality of life are likely to be improved. And, of course, none of these advances would be possible without continued funding for biomedical research and continued patient participation in clinical trials. This is the path by which new and better treatments will move from labs to patients.
Deborah Banker, Ph.D.