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Drug Discovery Revolutionized Bone Marrow Transplant

Drug Discovery Revolutionized Bone Marrow Transplant

John Hilton’s and Michael Colvin’s research more than three decades ago to decipher how the popular anticancer drug cyclophosphamide worked against cancer paved the way for major advances in bone marrow transplantation. The Kimmel Cancer Center’s first director, Albert Owens, and bone marrow transplant program leader George Santos performed research that used the drug at high doses instead of total-body radiation to destroy diseased bone marrow before transplanting patients with healthy donor marrow.

The first successful bone marrow transplant followed high-dose cyclophosphamide. Their early research also hinted at the usefulness of the drug after bone marrow transplant to limit the major complication of the procedure, graft-versus-host disease (GVHD), where the new donor immune system attacks the bone marrow and other normal tissues. These findings were pursued years later by Santos-trained bone marrow transplant expert Richard Jones and his colleagues. “Post-transplant cyclophosphamide revolutionized the field,” says Jones, director of the Cancer Center’s Hematologic Malignancies and Bone Marrow Transplant Program. His team continued the early cyclophosphamide research, expanding the drug’s ability to limit GVHD without harming the blood stem cells that give rise to new, healthy blood cells.

As a result of this work, today it is possible to do transplants in all patients, even those who do not have matching donors. GVHD limited the ability to do mismatched transplants in the past, but now, it is so well-managed—in large part due to cyclophosphamide—that nearly 95 percent of patients survive transplant, and it results in unmatched transplants that are the same as matched transplants. African-Americans, Hispanics and other minorities, who have historically been excluded from transplants because of the inability to find matching donors, now have the highest accrual to bone marrow transplant clinical trials in the history of the therapy.

Jones is excited about new research on the horizon, including combining transplant for solid tumors with anticancer agents to enhance immune reaction against cancers. A novel twist in prostate cancer research includes using bone marrow donated by daughters of patients. Women do not have prostates, so the immune system of the female donors will never have seen prostate cancer, a disease that only occurs in men, and should immediately recognize the cancer cells as foreign invaders. “All of these advances are possible because of cyclophosphamide,” Jones says

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