In patients with leukemia, peripheral blood stem cell transplants (PBSCT) and bone marrow transplant (BMT) have similar overall and leukemia-free survival even after 10 years of follow-up.
The data, now available online ahead of print in Lancet Oncology, is the largest randomized study of the two treatments to include a homogenous population in terms of conditioning regimen and graft source, said lead study author Birte Friedrichs, MD, of the Department of Hematology and Stem Cell Transplantation at Asklepios Hospital St. Georg, in Hamburg, Germany, and the Medical Clinic III, Charite-Campus Benjamin Franklin, in Berlin, Germany.
Additionally, no other randomized study has such a long follow-up period with a detailed analysis of graft versus host disease (GVHD), he said.
Asked for his opinion for this article, Armand Keating, MD, the Epstein Chair in Cell Therapy and Transplantation and Director of the Division of Hematology at the University of Toronto and Director of the Cell Therapy Program at Princess Margaret Hospital, said the findings are reassuring, because if has been a concern among hematologist-oncologists about there possibly being a survival difference between the two modalities.
Richard Champlin, MD, Chair of the Stem Cell Transplantation and Cellular Therapy Department at the University of Texas M. D. Anderson Cancer Center agreed: The study provides oncologists with good long-term data and confirms a number of previous reports, he said.
Dr. Friedrichs and his colleagues at the European Group for Blood and Marrow Transplantation compared outcomes of 329 patients with leukemia 10 years after undergoing a randomized matched sibling donor BMT or PBSCT between 1995 and 1999.
Staff at participating transplantation centers completed questionnaires about long-term events, chronic GVHD, late effects, and secondary cancers for patients surviving more than three years.
The 10-year overall survival rates were 49.1% for PBSCT patients and 56.5% for BMT patients, differences that were not statistically significant.
Patients undergoing PBSCT had an increased risk of developing chronic GVHD compared with those receiving BMT (73% vs 54%), and more PBSCT patients needed immunosuppressive therapy five years post-transplant (26% vs 12%). However, an increased risk of GVHD did not result in significantly increased mortality or affect general health status, return to work or late events.
While the incidence of GVHD was higher with longer immunosuppressive treatment, “we have to conclude that there can be given no recommendation that one of the graft sources is superior,” Dr. Friedrichs said.
One drawback of the GVHD analysis was that its impact on quality of life and social integration could only be estimated, because patients were not directly asked about these outcomes. To make an adequate assessment, patients need to be followed continuously after transplant, which is not always easy to achieve.
Additionally, while GVHD induction clearly depends on the graft source, its clinical course is related to many other factors such as infections, time of treatment initiation, and the type of treatment, and it can be difficult for one study to cover all these factors.
The researchers also found a nonstatistically significant trend toward improved leukemia-free and overall survival in patients with acute leukemia who underwent BMT. Those with acute lymphoblastic leukemia (ALL) had a 10-year overall survival rate of 33% with BMT vs 18% with PBSCT and a leukemia-free survival rate of 28% and 13%, respectively.
In patients with acute myeloid leukemia (AML) 10-year overall survival was 65.3% with BMT and 52.3% with PBSCT and leukemia-free survival was 62.3% and 47.1%, respectively.
While interesting, the study subanalyses indicating improved survival in patients with acute leukemias were insignificant and too small to draw any conclusions, cautioned Dr. Keating. Overall, the study subanalyses were hypothesis generating and require more research.
Chronic Myeloid Leukemia
An analysis of patients with chronic myeloid leukemia (CML) found survival rates between the two transplant groups to be similar. Ten-year overall survival in CML patients was 61% with BMT vs 57% with PBSCT, and the leukemia-free survival rates in those undergoing BMT and PBSCT were 40% and 48.5%, respectively.
However, because the study pre-dates treatment with imatinib, it doesn't inform the decision of using transplant in patients who are not responding to the drug or to second-line therapies, Dr. Keating noted.
CML patients whose disease is refractory to tyrosine kinase inhibitors should be considered for PBSCPT based on available data, the researchers wrote, citing a 2002 paper in Blood by Elmaagacli et al.
Patient, Donor, & Physician Preferences
Joseph H. Antin, MD, Chief of the Stem Cell Transplantation Program and Professor of Medicine at Harvard Medical School, commented that when deciding whether a patient should undergo BMT or PBSCT, criteria other than survival may be considered. Deciding what course of treatment to pursue is ultimately a doctor-patient-donor discussion.
For the donor, “it's a little easier and noninvasive to give peripheral blood cells,” Dr. Champlin said. “It's like giving blood at a blood bank and collecting platelets”—whereas with bone marrow harvest, the patient has to undergo general anesthesia for needle punctures on the iliac crest to withdraw the marrow.
In comparison, peripheral stem cell donors have to take filgrastim injections for about four days to raise their stem cell count before apheresis, and this medication can cause some bone pain. However, blood counts do recover more quickly than with bone marrow harvest, he added.
Dr. Antin noted that when all side effects are considered, the overall morbidity for donors of either bone marrow or peripheral stem cells is about the same.
The bottom line, however, Dr. Champlin said, is that many donors would prefer to be awake for donation rather than being under general anesthesia.
While there has been a shift toward using PBSCT, “the physician has an obligation to present the data to the patient and recommend the appropriate and best treatment option, including choice of graft when considering transplantation,” said Mary Eapen, MD, a pediatric oncologist at Children's Hospital of Wisconsin and Assistant Professor of Pediatrics at Medical College of Wisconsin.
GVHD should also be a consideration when deciding what treatment option to pursue. “GVHD increases morbidity and mortality,” she said. Although the study by Dr. Friedrich et al does not suggest a higher mortality after GVHD, other papers have, she said, citing Lee SJ et al: Blood 2002; 100:406-414 as an example.
GVHD may also increase the burden of morbidity (Fraser CJ et al: Blood 2006;108: 2867–2873), she added. “We've known for years that chronic graft-versus-host disease can be a problem for many people,” Dr. Antin said. If patients are concerned about GVHD, they might consider BMT.
Based on the results of the study by Dr. Friedrich's group, physicians who prefer BMT will use BMT and those who prefer PBSCT will continue to use PBSCT, Dr. Keating predicted.
While this research was informative, “we need to conduct further studies on cytogenetic and molecular risk factors and subsequent transplant outcomes,” Dr. Friedrichs said. Additionally, who benefits from early transplantation and to what extent GVHD and the graft-versus-leukemia effect occur in different disease subgroups need to be further examined.
Currently, studies are investigating the potential difference between bone marrow and PBSC in the matched-unrelated setting, Dr. Friedrichs said.
Also, said Dr. Antin, researchers are awaiting study results from the Blood and Marrow Transplant Clinical Trials Network trial and the National Marrow Donor Program of PBSCT vs BMT from matched unrelated donors.