Bone marrow transplant for the haemoglobinopathies: past, present and future

Bone marrow transplantation (BMT) is the only treatment currently available which can cure thalassaemia and sickle cell anaemia. However, it is not without risk and the complications of graft failure, GVHD, veno-occlusive disease, interstitial pneumonitis and infections, together with the toxicity of the conditioning therapy result in a transplant-related mortality in children of 10-20%. For the survivors, long-term sequelae include chronic GVHD, endocrinopathies and an increased incidence of secondary malignancies. The decision to offer BMT to a patient with a haemoglobinopathy must be based on a knowledge of the relative risks of transplant and conventional therapy. However, in sickle cell anaemia, a subset of patients with particularly severe disease can be identified at an early age when the risks associated with BMT are at their lowest. In thalassaemia, chelation therapy can delay the onset of organ damage due to hypertransfusion but is unlikely to prevent it entirely. The results of BMT in children without organ impairment are excellent and BMT must now be considered a real alternative to conventional treatment. Gene therapy is an exciting prospect for the future but recent progress in retroviral gene transfer has been hindered by poor infection efficiencies and expression levels in the target cells. The identification of the positive regulatory elements of both the alpha- and beta-globin genes may resolve some of these problems. Finally, alternative gene delivery systems are being investigated, but the introduction of gene therapy for the haemoglobinopathies into clinical practice may need to await successful gene targeting and replacement.