September 17, 2024
Key takeaways:
- Post-transplant cyclophosphamide prophylaxis reduced the OS disparity in matched vs. mismatched unrelated donor hematopoietic stem cell transplant.
- The approach could expand access to HSCT.
Use of post-transplant cyclophosphamide prophylaxis to prevent graft-versus-host disease could greatly expand access to hematopoietic stem cell transplantation, according to results of a retrospective study.
An analysis of patients who received post-transplant cyclophosphamide (PTCy) showed no statistically significant difference in OS or GVHD-free RFS (GRFS) between patients with matched (8/8) or mismatched (7/8) unrelated donors.
The ability to find a suitable unrelated donor with a 7/8 HLA match is “much greater” than finding one with 8/8 HLA match, according to researcher Steven M. Devine, MD, chief medical officer at NMDP and senior scientific director at Center for International Blood and Marrow Transplant Research (CIBMTR), told Healio.
“For an African American patient, [chances] go from 30% to over 80%,” Devine said. “It’s even higher for Hispanic or Asian individuals — into the 90% range.
“If you can go even lower [to a 6/8 match or 5/8 match], you can pretty much find a volunteer unrelated donor for almost 100% of patients,” Devine added. “We are enabling a transplant for everyone, regardless of their ancestry.”
Access disparities
Allogeneic HSCT — used to treat multiple blood cancers and blood disorders — produces the best results when stem cells of a related or unrelated donor matches at 8/8 HLA markers at the HLA-A, -B, -C and -DRB1 genes, according to study background.
Only 30% of patients have siblings, who are HLA-identical matches and therefore could donate.
Non-Hispanic white individuals have a 79% likelihood of finding an unrelated matched donor in the NMDP registry. The rate is between 29% and 58% for people of other races and ethnicities.
“Historically, there’s been roughly a 10% lower chance of survival with each level of mismatch,” Devine said. “That’s why for years the focus has been on trying to find full matches for all patients.”
Cyclophosphamide, a chemotherapy drug used to treat a variety of solid tumors and hematologic cancers, has been repurposed for about 20 years to prevent GVHD after HSCT.
“It’s really revolutionized [stem cell transplant] because its use is associated with a much lower risk for both the acute and more chronic forms of GVHD,” Devine said. “It’s improved outcomes overall, and it’s allowed us to perform mismatched transplants both from related and unrelated donors. So, [for this study], we [wondered whether] those historical differences in outcomes between matched and mismatched transplant [are] as great as they were years ago now that we’re using PTCy.”