ORLANDO, FL—The fear that donating stem cells for allogeneic transplant could increase the risk of cancer may have been keeping some individuals from volunteering. But now, as shown in a study reported here at the ASH Annual Meeting, potential donors can be reassured that donating bone marrow or peripheral blood stem-cells (PBSC) does not increase the risk of cancer or hospitalization.
The fear of possible long-term adverse events after donation stems from the use of G-CSF infusion to mobilize the donor's stem cells, and there have been reports in the literature of a potentially increased risk of leukemia, explained Alexander H. Schmidt, MD, PhD, Chief Medical Officer of German Bone Marrow Donor Registry (DKMS).
In the study reported here (Abstract 365), a total of 12,559 unrelated donors were asked afterwards about their overall health, number of hospitalizations, prescription drug use, and any diagnosis of cancer subsequent to the donation.
“There was no evidence for an increased malignancy risk related to donation, and a three-fold or stronger increase of leukemia risk due to donation could be excluded,” Dr. Schmidt said, noting that the DKMS (Deutsche Knochenmarkspenderdatei) is the largest bone marrow donor center in the world, with more than 2.5 million registered donors.
“Stem cell donation is a purely altruistic act by donors, so the safety of these volunteers is of the utmost importance,” Dr. Schmidt said.
He said the main challenge to mounting follow-up studies is the need for a very large number of individuals to continue supplying the data for many years.
“And since blood and bone marrow donors are largely healthy, they are not very motivated to follow up for many years, so the number of responses falls off rapidly and in a few years is less than 50%.”
He and his coresearchers decided, therefore, to send out only one, very simple questionnaire to 15,456 donors in the registry, asking about their general health status, hospitalizations or long-term medical treatment, prescription drugs taken, and their willingness to donate again.
Dr. Schmidt said this was not only the largest follow-up study on donors ever done, but that a remarkable percentage—81.3%—replied, translating into a total of 55,228 observation years (30,777 observation years for 8,730 PBSC donors, 23,037 observation years for 3,556 bone marrow donors, and 1,414 observation years for 273 donors of both PBSCs and bone marrow).
Regarding the question on the general well-being of donors, Dr. Schmidt said there were no relevant differences between the bone marrow or peripheral stem cell donors and the general population, and that the percentage who said their health was good or very good was very high—95.1% of PBSC donors, 96% of bone marrow donors, and 92.2% of dual donors.
It initially appeared that the rate of hospitalizations was lower for PBSC donors, but Dr. Schmidt said that after adjusting for age and gender (more males in this cohort and younger median age) there was no discernable difference.
More than 95% of donors said they would be willing to donate again.
“And among people who had donated both peripheral blood cells and bone marrow donation—that is, made at least two donations—more than 90% would be willing to donate again,” he said.
Incidence Ratio of Hematologic Malignancies
Dr. Schmidt's team calculated the standard incidence ratio for 85 malignancies—that is, the number of reported or observed cases divided by the number of expected cases.
“Among German donors we took incidences observed in total and we could not identify increased malignancy risks for hematologic malignancies.”
He said the observed standard incidence ratio for all malignancies and all donors was 0.99, suggesting that underreporting did not substantially affect the quality of the collected data on malignancies.
The data did show a small increased risk for bone marrow donors for malignant melanoma, but Dr. Schmidt said that appears to be a statistical artifact—“because there is no plausible mechanism to explain how a bone marrow donation could increase the risk of melanoma.”
Interestingly, the risk of lung cancer was much lower among donors than expected, with a standard incidence ratio of 1.15. There is speculation that stem-cell donors might have more interest in health matters and so would smoke less than the general population, “but this is only an assumption we cannot prove,” Dr. Schmidt said.
Only six cases of hematologic malignancies were reported: two of Hodgkin disease and one of plasmocytoma in PBSC donors; one case of acute myeloid leukemia and one case of non-Hodgkin lymphoma in bone marrow donors; and one case of chronic lymphocytic leukemia in dual donors.
Complement to Standard Follow-up
Dr. Schmidt said the study's once-only, retrospective approach led to high return rates, with the highest number of observations ever in relation to bone marrow and stem cell donation.
But he added that “a retrospective approach such as ours should not replace current prospective donor projects but could be a valuable complement to such programs.”
“We hope that these results underscore the fact that these donation procedures are extremely safe and will encourage more people to become donors,” Dr. Schmidt said.
Dr. Schmidt's report was one of those highlighted at an ASH media conference during the meeting. The moderator, ASH President-Elect Armand Keating, MD, Professor of Medicine and Director of the Division of Hematology at the University of Toronto, said he considered the study to be important, “because of the large number of individuals analyzed, the reasonable follow-up time of about four years, and for addressing in a reassuring way the low likelihood of increased malignancy, including leukemia, in donors who received G-CSF.”