A potential game-changer in blood and marrow transplantation

Dr. Marco Mielcarek, professor (Hematology and Oncology) and medical director of the Fred Hutch Blood and Marrow Transplant Program, has received a five-year, $3.5 million NIH U01 collaborative research grant to complete a clinical trial and related laboratory research projects to determine the optimal dosage for a drug used to prevent one of the most common illnesses associated with transplanting stem cells sourced from a donor’s bone marrow or peripheral (circulating) blood: graft-vs.-host-disease, or GVHD.

The funding will allow Mielcarek and collaborators at the National Cancer Institute and City of Hope to complete a dose de-escalation study for post-transplantation cyclophosphamide (PTCy). The Phase I/II clinical trial aims to identify whether lower doses of PTCy can have the same positive impact in reducing GVHD while reducing side effects associated with the drug.

“The overall goal is to make [the PTCy treatment] less toxic by being able to reduce the dose,” said Mielcarek. “The current dose, which has never been systematically optimized, has room for improvement in terms of organ toxicities such as mucositis [the inflammation of mucous membranes in the digestive tract] and heart failure. There is also a risk of delayed immune reconstitution and increased rates of certain infections. So, a lower dose would be great if it could be achieved without compromising cyclophosphamide’s ability to prevent GVHD.”

The grant was initially submitted as an R01, one of the most prestigious multi-year research grants awarded by the NIH. After the funding decision was made, it was converted to a U01, a classification reserved for collaborative projects in which NIH scientists will be significantly involved in the project.

The study could lead to advances in the standard of care for BMT recipients, resulting in improved quality of life and survival rates.