It is a downhill descent Mary Horowitz, M.D., has never seen. Every year, the slides she has prepared as scientific director of the International Bone Marrow Transplant Registry have shown increasing use of high-dose chemotherapy and stem cell support. The numbers just in for 1999, however, point precipitously downward.
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She also sees a somewhat similar trend for allogeneic transplants, which use donor stem cells instead of a patients own stored blood to restore immunity. From 1996 through 1998, physicians reported about 3,100 procedures. But in 1999, that flat curve headed downward as 2,800 allogeneic transplants were reported.
Whats going on?
Horowitz sees the answer on several levels. One has to do with fallout from reports of mediocre performance of autotransplants for breast cancer, results that were reported in May 1999 at the annual meeting of the American Society of Clinical Oncology. "Bad press for autologous transplants have a ripple effect for transplants in general," she said.
The other is based on additional factorsthere has been no widely successful new use of autologous transplants in recent years, and while high-dose chemotherapy and allogeneic transplants can offer a new immune system to patients, the 20% mortality rate associated with the procedure remains an impediment. Comparatively, about 3% to 5% of patients treated with autotransplants die from effects of the treatment.
"The question remains if these transplants will remain a part of a platform of targeted therapy," Horowitz said.
Decline for Solid Tumors
High-dose chemotherapy and autotransplantation is the treatment of choice for most relapsed lymphoma patients who are considered candidates for intensive therapy. "Any healthy person with relapsed lymphoma is automatically referred to autologous transplant," said American Cancer Society oncologist Herman Kattlove, M.D. There is even new research published in October in the journal Blood suggesting its beneficial use in primary refractory aggressive non-Hodgkins lymphomalymphoma that does not respond to traditional chemotherapy doses.
The procedure is also seen by many as the best way to increase survival in multiple myeloma, which is incurable. Its use has steadily continued for the past 5 years, from 530 procedures in 1996 to about 1,200 in 1999.
But its use in solid tumors remains extremely controversial. It has been tried in lung cancer and brain tumors, but for all intents and purposes, "autotransplants remain experimental in all solid tumors, with the exception of testicular cancer," said Craig Nichols, M.D., professor of medicine in the Department of Hemaotology/Oncology at the Oregon Health Sciences University.
He showed in a study published Oct. 3 in the Journal of Clinical Oncology that use of autologous transplantation is associated with substantial cure rates for testicular cancer patients who experience cancer recurrence.
But others say the jury is still out on breast cancer. "The ASCO studies were very preliminary, like announcing the winner of a marathon after only 10 miles were run. It has allowed physicians to misinterpret the results, which is a disservice to patients," argued Scott Bearman, M.D., director of the Bone Marrow Transplant Program at the University of Colorado Health Sciences Center. Even though he is continuing studies of the therapy in breast cancer, including a novel look of autotransplantation followed by a nonmyeloablative "mini" allogeneic transplant, Bearman says his center has experienced an 80% reduction in use of autotransplantation for advanced breast cancer.
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Blood Cancers
Allogeneic transplantationreplacing a patients immune system with one that is similarplays a role in cancers of the blood such as leukemia. The hope is that the new stem cells will not only replace the patients own, but will recognize the cancer cells as foreign and fight them.
Allogeneic transplants have remained the treatment of choice for a variety of leukemias that have relapsed or not responded to traditional treatment. These leukemias include acute myelogenous leukemia, acute lymphocytic leukemia, and chronic myelogenous leukemia. Last year, there were fewer reported transplants for CML, due to the availability of a promising new drug therapy.
Allogeneic transplants have been tested against autotransplants for treatment of leukemia, and while both offer equivalent survival, their particular deficits came to light. Stephen Nimer, M.D., head of the Division of Hematology-Oncology at Memorial Sloan-Kettering Cancer Center, New York, said that patients with autotransplants tended to die from cancer relapse, while patients receiving allogeneic transplants tended to succumb to the treatment itself.
Future of Therapy
Some researchers contend that high-dose chemotherapy may not be necessary at all. "There is a big move away from high dose chemotherapy in a lot of malignancies. The evidence is compelling that autologous transplants are a big disappointment. They are unlikely to cure anyone," said Richard Childs, M.D., of the National Heart, Lung, and Blood Institute.
Childs believes that many physicians are more interested in the immunological aspects of allogeneic transplants, and he is investigating the use of mini transplants for solid tumors such as colon, breast, pancreatic and liver cancer. He concluded in a study published in the Sept. 14 New England Journal of Medicine that mini allogeneic transplants offer a year or more of survival for half of patients with advanced kidney cancer a cancer that usually doesnt respond to chemotherapy.
Nimer agrees that enhancing a patients immune system will become increasingly useful but sees a different future. He thinks high-dose chemotherapy with stem cell rescue will be critical to the treatment. That procedure will result in a minimal state of disease, which can then be followed by "post transplant immunotherapy, antibody-based or a vaccine" to boost the patients own ability to fight the cancer.
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