20 March 2019

Bone marrow transplant patients given ‘half-matched’ donor cells achieved almost 100% engraftment rate when the amount of total body radiation was doubled, researchers have reported.

The study, led by John Hopkins University, Baltimore, USA, could lead to a higher chance of a cure for patients with severe and deadly haemoglobinopathies including sickle cell anaemia and β‑thalassaemia.

Prof Robert Brodsky, professor of medicine and oncology research at the Johns Hopkins University School of Medicine, described the findings as “exciting”.

“These results are really exciting as we're approaching a 90% cure rate for sickle cell and beta thalassaemia,” he said.

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

It was discovered in the 1980s that bone marrow transplants could potentially cure sickle cell disease. However, the treatment has only been used sparingly because it required bone marrow donors and recipients to fully match each other in human leukocyte antigens that are displayed on cells.

Johns Hopkins researchers developed a protocol, published in 2012, that allows patients to receive transplants from relatives who are only half-matched, which significantly expanded the pool of potential donors.

However, the resulting transplants only engrafted to produce healthy new blood about half of the time.

In this latest study, published in The Lancet Haematology, Dr Javier Bolaños-Meade and his colleagues tested a new protocol for bone marrow transplants in patients with severe sickle cell disease and β-thalassaemia, enrolling 17 patients for the study: 12 with sickle cell disease and five with β-thalassaemia.

Each of these patients had a relative who could serve as a half-match for a bone marrow transplant.

They received doses of chemotherapy and total body irradiation to knock down their immune response to the donor bone marrow before transplant.

However, instead of receiving 200 centigray (cGy) of radiation, patients in the new study received 400 cGy. After their transplants, they all received cyclophosphamide, which is used to prevent graft versus host disease, which is prevalent with half-matched bone marrow donations.

The patients’ blood was tested for chimerism on day 30, 60, 180 and 360 and annually after that.

They found that all the patients, except one with sickle cell disease, had successfully engrafted. Five developed graft versus host disease, but the condition resolved in each of these patients. All but three patients have stopped taking immunosuppressive medications.

All of those with successful engraftment reported that the symptoms of their disease were significantly reduced or they had no symptoms. The researchers also found that the β-thalassaemia patients were no longer dependent on blood transfusions.

Prof Richard Jones, director of the Johns Hopkins Kimmel Cancer Center bone marrow transplantation program, said: “These latest findings add to an extensive and growing body of evidence supporting the safety and effectiveness of half-matched bone marrow transplants.

“We have performed more than 1,000 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.”

Source: Bolaños-Meade, J., Cooke, K.R., Gamper, C.J., Ali, S.A., Ambinder, R.F., Borrello, I.M., Fuchs, E.J., Gladstone, D.E., Gocke, C.B., Huff, C.A., Luznik, L., Swinnen, L.J., Symons, H.J., Terezakis, S.A., Wagner-Johnston, N., Jones, R.J., Brodsky, R.A. (2019) “Effect of increased dose of total body irradiation on graft failure associated with HLA-haploidentical transplantation in patients with severe haemoglobinopathies: a prospective clinical trial”, The Lancet Haematology, available at doi: 10.1016/S2352-3026(19)30031-6


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