PBSCs from unrelated donors linked to higher rates of chronic GVHD

53rd ASH Annual Meeting

SAN DIEGO — Patients assigned to filgrastim-mobilized peripheral blood stem cells from unrelated donors did not experience a survival benefit and were more likely to develop chronic graft-versus-host disease compared with patients assigned to receive bone marrow from unrelated donors.

Additionally, phase 3 results from BMT CTN protocol 0201, a prospective, randomized trial, showed that rates of acute graft-versus-host disease (GVHD), relapse, non-relapse mortality and OS were similar between the two treatments.

From January 2004 to September 2009, researchers at 50 centers in the United States and Canada randomly assigned 278 patients with a variety of high-risk leukemias to bone marrow transplantation and another 273 patients to peripheral blood stem cell (PSBC) transplantation. The median follow-up was 36 months.

Claudio Anasetti, MD, chair of the department of blood and marrow transplant at Moffitt Cancer Center in Tampa, Fla., presented the results at the 53rd Annual Meeting of the American Society of Hematology.

Although PBSCs from related donors have been shown to have clinical benefit, Anasetti told HemOnc Today that these results show that PSBCs from unrelated donors put patients at greater risk for chronic GVHD without conferring similar benefits. Survival was identical between the two treatment groups.

“Acute GVHD is not different, but the chronic GVHD is about 15% higher, especially the chronic extensive GVHD, which requires immune suppression and keeps patients at higher risk for disability and death even after 2 years,” he said. “At 2 years, 20% more patients who received PBSC require immunosuppressive drugs.”

Engraftment was more robust and more consistent for patients assigned to PBSCs, but those patients were more likely to die of GVHD, Anasetti said. Bone marrow recipients were more likely to die of graft failure.

Researchers did not observe any difference between the two groups for OS, relapse or non-relapse mortality, he said. Patients assigned to PSBCs had a higher incidence of overall chronic GVHD (53% vs. 40%) and more common chronic extensive GVHD with PBSC (46% vs. 31%).

Patients undergoing myeloablative therapy are more likely to do better with bone marrow transplantation unless they are at increased risk for engraftment failure or they have active infection, Anasetti said. However, it is not clear whether patients undergoing reduced intensity conditioning, who are at greater risk for graft rejection, would benefit from PBSCs.

“The focus in bone marrow transplants should be on improving engraftment, either by modifying conditioning regimens or employing new technology to facilitate engraftment,” he said. “The big question, in my view, remains the prevention of acute and chronic GVHD. If you look at causes of death across the whole of the study, more patients died of acute and chronic GVHD than any other cause. A clinical trial addressing the issue of prevention of acute and chronic GVHD in the reduced-intensity population is probably what is most needed at this time.” – by Jason Harris

Disclosure: Dr. Anasetti reports no relevant financial disclosures.

Brian Bolwell

The follow-up to this study is only a few years, and there is concern that the ongoing morbidity of chronic GVHD may lead to inferior results. It certainly leads to morbidity to the patients. Based on these results, at the very least we can say that for matched, unrelated transplant, there is no benefit to giving peripheral blood progenitor cells if you look at population as a whole. There may be reasons, nevertheless, to still give peripheral stem cells in that setting. These cells tend to engraft quicker, and sometimes that’s important. There may be donor preference. There is another study to be presented here that shows PBSCs may be beneficial in related transplants. One has to ask whether there is a difference between related and unrelated transplants when comparing marrow vs. peripheral stem cells.

Brian Bolwell, MD
Chairman of Taussig Cancer Institute at Cleveland Clinic

Disclosure: Dr. Bolwell reports no relevant financial disclosures.

For more information:

• Anasetti C. Abstract #1. Presented at: 53rd Annual Meeting of the American Society of Hematology; Dec. 10-13, 2011; San Diego.

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