SEATTLE – A decade of refinements in marrow and stem cell
transplantation to treat blood cancers significantly reduced the
risk of treatment-related complications and death, according to an
institutional self-analysis of transplant-patient outcomes
conducted at Fred Hutchinson Cancer Research Center.
Among the major findings of the study, which compared
transplant-patient outcomes in the mid-'90s with those a decade
later: After adjusting for factors known to be associated with
outcome, the researchers observed a statistically significant 60
percent reduction in the risk of death within 200 days of
transplant and a 41 percent reduction in the risk of overall
mortality at any time after transplant.
"Everything we looked at improved a decade after the initial
analysis," said George McDonald, M.D., a Hutchinson Center
gastroenterologist and corresponding author of the paper, which was
published (date) in the New England Journal of Medicine.
McDonald and colleagues reviewed the outcomes of 1,418
transplant patients who received peripheral-blood stem cells or
bone marrow from unrelated donors between 1993 and 1997 and
compared them to 1,148 patients who had the same procedures between
2003 and 2007. The malignancies treated included forms of leukemia,
lymphoma, multiple myeloma and myelodysplastic syndrome.
The researchers also found that the estimated one-year overall
survival rates for both groups were 55 percent and 70 percent,
respectively. They also observed statistically significant declines
in the risks of severe graft-vs-host-disease; infections caused by
viruses, bacteria and fungi; and complications caused by damage to
the lungs, kidney and liver.
Lead author and biostatistician Ted Gooley, Ph.D., noted that
the analysis presents the findings in terms of the changes in the
"risk" or "hazard" of death and transplant complications after
taking into account the fact that the patients treated in the
mid-2000s were, on average, older and sicker than those who were
treated in the mid-1990s.
McDonald said he and his colleagues can only speculate about the
reasons for the improved outcomes because the study was
retrospective and was not a randomized comparison of transplant
techniques and treatments among groups of patients. However, the
authors deemed several changes in clinical practices to be
important in risk reduction, many of which were the result of
ongoing clinical research (including various randomized clinical
trials) conducted at the Hutchinson Center and at other major
transplant centers around the world:
- Careful pharmacologic monitoring and dose adjustments to avoid
under and over treatment with the potent chemotherapeutic agents
used in transplantation.
- Use of reduced-intensity conditioning in older and less healthy
patients.
- Less use of high-dose systemic immune suppression to treat
acute GVHD.
- Use of the drug ursodiol to prevent liver complications.
- New methods for early detection of viral and fungal infections
as well as preventive therapy for such infections.
- The use of better and less toxic anti-fungal drugs to treat
serious infections caused by Candidal organisms and molds.
- Use of donor peripheral blood hematopoietic cells instead of
bone marrow as the source of donor cells, which results in faster
engraftment and return of immunity.
- More accurate matching of marrow or stem cell donors with
unrelated patients.
"This research and the improved outcomes are the result of a
team approach to one of the most complex procedures in medicine,"
McDonald said. Medical oncologists and transplantation biologists
at the Hutchinson Center are supported in the care of patients by
specialists in infectious diseases, pulmonary and critical care
medicine, nephrology, gastroenterology and hepatology, and by
highly skilled nurses and support staff.
"Each of these programs is involved in ongoing clinical research
into the complications of transplant, which results in constant
changes in how transplantation is carried out," he said. "These
data show clearly that our collective efforts have improved the
chances of long-term survival for our patients."
SOURCE