Doctors from The National Institute of Health, Bethesda and The John Hopkins Medical School reported the first 10 adult patients with sickle cell disease, who they transplanted with reduced intensity conditioning (RIC), in 2009. This month they published an update to this study in the Journal of the American Medical Association (JAMA. 2014; 312: 48-56). They have now transplanted a total of 29 adult patients with sickle cell disease (Hb SS 25; Hb SC 2; Hb S beta-thalassaemia 2) with an age range of 16 to 65 years, many of whom had significant chronic organ damage from their condition.
All the transplants were with peripheral blood haemopoietic stem cells collected from closely matched, sibling donors. Prior to transplantion treatment with hydroxycarbamide was continued and every patient had an exchange red cell transfusion to reduce the haemoglobin S level to less than 30%. Pre-transplant conditioning was with alemtuzumab and low dose total body irradiation (TBI) and post-transplant immunosuppression was with sirolimus.
Long term, stable engraftment was achieved in 86% (25 patients). 4 patients (14%) rejected the graft and reverted back to their sickle cell disease. One of these 4 patients died some months later from a brain haemorrhage. There were no deaths directly linked to the transplant procedure. Infectious complications were common but treatable; the majority of patients required treatment with IV antibiotics in the immediate transplant period for presumed bacterial infections; 24% (7 patients) required treatment for re-activated viral infections and 1 patient was treated for a fungal infection. Remarkably there were no cases of GvHD. 48% (15 patients) were eventually able to stop immunosuppressive treatment with sirolimus completely.
All the patients who had stable engraftment of the new bone marrow developed donor:recipient chimerism. Nevertheless, all their symptoms of sickle cell disease resolved, admissions to hospital virtually ceased and all those with chronic pain, requiring long term morphine-like pain relief, were able to stop the use of pain killing medication. These are remarkable results proving that adult patients, even those with severe, disabling disease, can be safely transplanted and cured of their sickle cell disease.
Recruitment of patients to this trial continues. The team are hoping to expand the number of eligible adult patients, by adapting their transplant protocol so that they can use haploidentical donors, instead of restricting the transplants only to those patients with closely matched sibling donors..