Bone marrow transplant cures blood diseases

Patients with severe and deadly inherited blood disorders may soon have a 100% cure rate, thanks to a new protocol that combines a bone marrow transplant with radiation. 

Described in the The Lancet Haematology, the treatment could offer a significantly higher chance of a cure for patients with inherited blood disorders, including sickle cell anaemia and beta thalassemia.

The Lancet study found that a ‘half-matched’ donor’s cells, combined with a doubling of the low amount of total body radiation delivered to patients undergoing bone marrow transplants, increased the rate of engraftment from only about 50% to nearly 100%.

“Bone marrow transplants are not just for patients with a perfectly matched donor. A half-match is definitely good enough,” said Dr Robert Brodsky, a 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.

In the late 1980s, 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. Until recently, it required bone marrow donors and recipients to fully match each other in a set of proteins known as human leukocyte antigens that are displayed on cells. Without a complete match, Dr Brodsky says, the recipient’s body recognises donor cells as foreign and launches a destructive attack.

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 developed a protocol, published in 2012, that allows patients to receive transplants from relatives who are only half-matched. This advance significantly expanded the pool of potential donors, Dr 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, the researchers tested a new protocol for bone marrow transplants in patients with severe sickle cell disease and beta thalassemia, two related blood disorders known as haemoglobinopathies that are caused by defects in the same beta-globin gene. They found that all the patients, except one with sickle cell disease, had successfully engrafted — a rate significantly higher than that seen with the previous protocol. Although five developed graft versus host disease, the condition resolved in each of these patients.

At the time of the study’s publication, only three patients still needed to take immunosuppressive medications. All of those with successful engraftment had either extreme reduction or no symptoms of their disease — the sickle cell disease patients no longer had the pain crises that are hallmarks of their condition. Similarly, the beta thalassemia patients were no longer dependent on blood transfusions.

“These latest findings add to an extensive and growing body of evidence supporting the safety and effectiveness of half-matched bone marrow transplants,” said Dr Richard Jones, Director of the Johns Hopkins Kimmel Cancer Center bone marrow transplantation program. “We have performed more than 1000 half-matched bone marrow transplants, and our clinical studies have proved so successful, with safety and toxicity comparable to matched transplants, that half-identical transplants must be made available to more patients as a curative option.”

Only mild, low-dose (or ‘mini’) therapy is needed to allow the transplant to take, making the transplant potentially safer for patients with sickle cell disease and thalassemia who are often unable to tolerate the high-dose (myeloablative) therapy needed for gene therapies to take, Dr Jones says.

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