Hutch scientists have confirmed the promise of stem-cell transplantation as a cancer therapy with a study showing that the technique offers clear benefits over bone-marrow transplants for patients with high-risk cancers.
Patients with advanced blood cancers may experience fewer complications, speedier recovery and improved relapse and survival rates when treated with stem-cell transplants as compared to traditional bone-marrow transplants, according to the study. The findings were published in the Jan. 18 edition of the New England Journal of Medicine.
The results of the comparative study, led by the Clinical Research Division's Dr. William Bensinger and co-authored by collaborators at Stanford University and City of Hope Medical Center in Duarte, Calif., may encourage more widespread use of stem-cell transplantation to treat a variety of leukemias and other blood disorders.
"The results are exciting because most strategies aimed at reducing relapse are associated with higher toxicities, more complications and higher mortality," said Bensinger, also an associate professor at the University of Washington School of Medicine. "These data suggest that stem-cell transplants may offer the best of both worlds, fewer relapses with fewer complications."
The study of 172 patients evaluated the incidence of acute and chronic graft-vs.-host disease, a potentially life-threatening complication of transplantation, and the rate of growth of donor cells in patients who underwent a marrow or stem-cell transplant from a tissue-type matched family member donor between March 1996 and July 1999.
The incidence of acute graft-vs.-host disease was 57 percent with marrow and 64 with stem cells, while chronic graft-vs.-host disease was lower, with the incidence of 34 percent with marrow and 46 percent with stem cells.
An unexpected result of the study was an increased survival rate for advanced cancer patients transplanted with stem cells versus bone marrow. Researchers found 45 percent of the patients undergoing marrow transplant and 65 percent undergoing stem-cell transplants were disease-free after two years.
Although encouraged by this finding, Bensinger cautioned that the survival-rate increases must be verified by additional studies designed to look at this outcome directly.
Bensinger said the improved treatment outcome using stem-cell transplantation was most significant for patients with advanced disease, who are more likely to relapse after conventional therapy.
"The evidence is convincing enough that we've already made a change in treating our high-risk patients," he said. "For patients with accelerated phases of chronic or acute leukemia, and patients who are beyond first remission or have refractory (nonresponsive) relapses, we are using stem cells."
While the benefits of using stem cells over marrow for low-risk patients is not yet clear and will require more studies, Bensinger is optimistic.
"This could open up other options for many patients, but more work needs to be done to define the value of stem cells in less-advanced cases and in cases using unrelated donors," he said.
Bensinger speculated that stem cells from peripheral blood may be more effective in treating cancers both because they are functionally different from marrow stem cells and because they are present in larger numbers. Patients undergoing stem-cell transplants also receive large numbers of T cells, a type of white blood cell with cancer-fighting activity.
The Hutch has been a pioneer in successfully treating cancer patients using marrow transplantation, a technique in which diseased marrow is replaced with healthy marrow from a tissue-matched donor. The technique requires the patient's own marrow - which produces blood and immune cells - to be destroyed with radiation and chemotherapy, followed by infusion of donor tissue. If the transplant is successful, donor cells will "engraft" and form an entirely new blood and immune system for the recipient.
Bensinger said using stem cells offers advantages to donors as well as cancer patients.
Donating stem cells is easy, akin to giving blood. Isolating bone marrow from a donor is an operative procedure requiring anesthesia. Marrow is typically removed from a donor's hip bones using syringes with very large needles which must be injected multiple times to obtain the appropriate quantity. Donors experience soreness for several days after marrow aspiration.
Bone marrow is a spongy tissue that contains stem cells, undifferentiated cells that have the potential to develop into all of the more specialized blood and immune cells necessary for life. But stem cells also circulate in the blood, making it possible to isolate these lifesaving cells using a much less painful method than marrow aspiration.
For stem-cell collection, donors are given a series of injections to stimulate stem cell growth for four to five days before their blood is collected by a technique called apheresis, which separates and collects the white cell fraction - which contains the stem cells - of the blood. The donor is attached to the apheresis machine with an intravenous line, requiring no anesthesia.
Bensinger said that because most insurance companies that cover bone-marrow transplants from related donors also cover stem-cell transplants, the procedure should be widely available to patients who might benefit.