MIAMI BEACHAs more cancer patients undergo allogeneic and
autologous peripheral blood stem cell (PBSC) and bone marrow
transplants, more long-term complications crop up. Two papers
presented at the ASH meeting addressed the late effects of reduced
bone density and development of therapy-related leukemia.
Bone density loss after solid tumor organ transplant has been
documented, and is commonly related to pretransplant health status,
organ dysfunction, and post-transplant immunosuppressive therapy.
Likewise, cancer patients receiving PBSC or bone marrow transplants
may face similar bone thinning.
Keith M. Sullivan, MD, and colleagues at the Fred Hutchinson Cancer
Research Center and the University of Washington, Seattle, examined
the incidence, severity, and onset of bone density abnormalities
during the first year after allogeneic PBSC transplant.
Their longitudinal study measured bone density by dual energy x-ray
absorptiometry (DEXA) at 3 and 12 months after transplant to
determine the tempo and degree of bone density loss and its
associated risk factors.
We know very little about bone loss following stem cell
transplant, Dr. Sullivan commented, and, with young
adults, this will be an issue for their long-term survival.
Dr. Sullivan reported results on 104 adults (52 women and 52 men),
ranging in age from 18 to 66, without prior bone disease. DEXA scans
of the hip at 3 months showed that 44% of the patients already had
low bone density scores, and 4% of the patients had developed
osteoporosis. In 35% of patients, the researchers observed low spine
density (osteopenia); in 8% of patients they observed osteoporosis of
the spine. We found that the older the patient, the higher the
risk for osteopenia, Dr. Sullivan said. There appeared to
be no gender effect and no effect from use of total body irradiation.
Also highly significant was cumulative prednisone use. Significant
associations between chronic graft-versus-host disease and change in
hip and spine density were presumably due to prednisone therapy, he said.
We dont yet know the most effective type and duration of
routine preventive therapy, Dr. Sullivan said, but
because osteopenia is so common after stem cell allografting, it is
essential to prevent osteoporosis early after transplant. Future
studies should carefully examine the value of interventions to
minimize the risk of bone disease and later morbid-ity in these patients.
At the City of Hope National Medical Center, Duarte, Calif, A.
Krishnan, MD, and colleagues focused on the risk factors for
developing therapy-related leukemia (myelodysplasia or AML) after
autologous transplantation for lymphoma.
Its not clear whether this well-known complication of
therapy for Hodgkins disease and non-Hodgkins lymphoma
represents the effects of pretransplant treatment, or results from
transplant conditioning and/or stem cell priming, Dr. Krishnan said.
City of Hope researchers followed 612 patients (median age, 39)
undergoing autologous transplants for lymphoma. Twenty-two patients
developed morphologic evidence of therapy-related leukemia post-transplant.
Compared with a control group matched for disease and length of
follow-up, there were no significant links between the development of
leukemia and age at transplant, exposure to pretransplant alkylating
agents, prior local radiation, or transplant conditioning regimens.
However, Dr. Krishnan said, stem cell priming with high-dose
etoposide was independently associated with increased risk of
leukemia with genetic abnormalities (11q23/21q22).
In the cohort study, patients who received PBSCs were more likely to
develop myelodysplasia or AML than patients who received bone marrow
alone or bone marrow and peripheral blood stem cells.
We need prospective studies with more sensitive biomarkers from
the time of diagnosis in order to determine the sequence of events
that ultimately leads to therapy-related leukemia, Dr. Krishnan concluded.