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Preventing GVHD and Improving Outcomes for Stem Cell Transplant

By Brian C. Betts, MD, Vice Chair of Strategic Initiatives at Roswell Park Comprehensive Cancer Center 


Several factors contribute to improving the success and safety of allogeneic stem cell transplant. At Roswell Park, we deploy three key strategies to help our patients achieve better outcomes and quality of life.

  • Use of post-transplant cyclophosphamide (PTCy) graft versus host disease prophylaxis for matched related and unrelated, mismatched unrelated, and haploidentical donor transplant procedures
  • Prioritizing younger donor age in the PTCy era
  • Minimizing the duration of immune suppression in the PTCy era

Effective GVHD prophylaxis

We use PTCy-based GVHD prophylaxis for all donor sources in the allogeneic setting. PTCy was developed as a GVHD prevention strategy for haploidentical transplantation but was later shown to be incredibly effective for related and unrelated donor transplants, regardless of match grade. By using PTCy, life-threatening acute GVHD is less than 10%, when we used to experience rates of 25% or even higher only 2 or 3 years ago.

This strategy has also reduced the risk for chronic GVHD requiring systemic immune suppression from 40-60%, down to 5-10%. This means number of patients requiring systemic immune suppression is also reduced, allowing us to avoid some other significant side effects such as infections, diabetes, and bone problems due to prolonged use of glucocorticoids. The fact that we can avoid all that and just make quality of life better for our patients and have better odds of curing them is fantastic.

Prioritizing donor age < 40

There is clear and consistent data showing the use of donors under 40 years of age improve outcomes for transplant recipients. Traditionally, determining an appropriate stem cell donor meant matching eight of eight human leukocyte antigens (HLA). While match-grade is still important, the use of PTCy allows us to tolerate HLA-mismatches of 6 or 7/8 and focus on identifying younger donors to improve transplant success.

So, our first choice is a fully matched, related donor, younger than age 40. If we don’t have that we look at a matched, unrelated donor, also younger than age 40. Data from several multicenter sources now show the use of PTCy with mismatched donors yield phenomenal results. Therefore, our primary alternative donor source is a 6 or 7/8 HLA matched unrelated donor, followed by a haploidentical donor. This allows us to find donors for many more patients — and younger donors than we used to — improving health equity and transplant outcomes.

Reducing the duration of immune suppression

PTCy-based regimens, such as PTCy paired with tacrolimus and mycophenolate mofetil, permit the efficient and early taper of immune suppression. Several years ago, patients could remain on immune suppression for months or even years, with unsuccessful or choppy patterns in tapering GVHD prophylaxis. With PTCy-based regimens, we aim to start the immune suppression taper by two to three months post-transplant, with patients off by four to six months post-transplant. This limited exposure to immune suppression greatly reduces the overall burden of infections and risk for relapse. This approach also allows a smooth, and likely earlier, handoff to the referring oncologist to assist us with managing post-transplant maintenance, where appropriate, to reduce relapse risk.

Generally, PTCy-based GVHD prophylaxis is highly effective, facilitates early discontinuation of immune suppression, and facilitates the integration of post-transplant maintenance therapy. In a sense, PTCy mediates safe and effective passage for patients through the early post-transplant course to help them return home in a timely manner and enhance quality of life.

The ultimate goal for our allogeneic transplant patients is to be cured of the malignancy, successfully discontinue immune suppression, and return to the care of their referring oncologist and primary care team well by their two-year post-transplant anniversary.

Refer a patient for a stem cell transplant consult. 


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