Doubling the low amount of total body radiation delivered to patients undergoing bone marrow transplants with donor cells that are only “half-matched” increased the rate of engraftment from only about 50 % to nearly 100 %, according to a new study by Johns Hopkins researchers. The findings, published online Mar. 13 in The Lancet Haematology, could offer a significantly higher chance of a cure for patients with severe and deadly inherited blood disorders including sickle cell anemia and beta thalassemia.

Oncology research

“These results are really exciting as we’re approaching a 90 %t cure rate for sickle cell and beta thalassemia;” says Robert Brodsky, M.D., professor of medicine and oncology research at the Johns Hopkins University School of Medicine; director of the Division of Hematology; and a member of the Johns Hopkins Kimmel Cancer Center. “Bone marrow transplants are not just for patients with a perfectly matched donor. A half-match is definitely good enough.”

In the late 1980s, explain study leaders Javier Bolaños-Meade, M.D., associate professor of oncology at the Johns Hopkins Kimmel Cancer Center, and Brodsky, researchers discovered that bone marrow transplants could potentially cure sickle cell disease; a condition with few effective treatments and one that typically kills patients in their 40s. However; this treatment has only been used sparingly since then.

Until recently, it require bone marrow donors and recipients to fully match each other in a set of proteins know as human leukocyte antigens that are display on cells. Without a complete match, Brodsky says; the recipient’s body recognizes donor cells as foreign and launches a destructive attack.

Researchers developed a protocol

Since finding a full match is difficult in this patient population fewer than 15 % have fully matched siblings free of the same genetic defect that causes sickle cell disease; and less than a quarter have full matches in unrelated registries Johns Hopkins researchers develop a protocol, published in 2012; that allows patients to receive transplants from relatives who are only half-match.

This advance significantly expanded the pool of potential donors, Brodsky says, but the resulting transplants only engrafted to produce healthy new blood about 50 % of the time. Seeking to increase the odds of engraftment for these half-matches; Bolaños-Meade and his colleagues tested a new protocol for bone marrow transplants in patients with severe sickle cell disease and beta thalassemia; two relate blood disorders known as hemoglobin that are cause by defects in the same beta-globin gene.

Particularly prevalent

They recruited 17 patients for the study: 12 with sickle cell disease and five with beta thalassemia; with a median age of 16. Each of these patients had a relative who could serve as a half-match for a bone marrow transplant siblings; mothers, fathers and one aunt. As in the previous protocol; all received doses of chemotherapy and total body irradiation to knock down their immune response to the donor bone marrow before transplant.
Rather than receiving 200 centigray (cGy), the low dose of radiation delivered in the previous protocol; patients in the new study receive 400 cGy still a relatively small amount of radiation that was well-tolerate. After their transplants; all receive a dose of cyclophosphamide; a drug that has proved critical to avoiding a potentially deadly condition know as graft versus host disease that is particularly prevalent with half-matches.