乌鸦传媒

SAN DIEGO -- New approaches to stem cell transplantation and gene therapy showed promise in treating, and possibly even reversing, sickle cell disease (SCD), researchers said here.

In one study, a parental-donor transplant technique seemed to provide SCD patients with more options for finding suitable allogeneic transplant donors, reported Mitchell Cairo, MD, of New York Medical College in Valhalla, New York, and colleagues, in a presentation at the American Society of Hematology annual meeting.

Currently, the only cure available for SCD is a stem cell transplant using cells donated by a sibling who doesn't have SCD, who has the same tissue type, and has the same mother and father. With these restrictions, only about 15% of patients with SCD has a sibling who is a suitable donor.

Cairo and colleagues investigated the possibility of a haploidentical transplant, a modified form of stem cell transplant in which a healthy first-degree relative -- such as a parent -- could be a suitable donor.

The problem with this type of transplant has been a high failure rate. To counter that, Cairo's group enriched stem cells with a protein called CD34, with the understanding it promotes the acceptance of transplanted blood-forming cells. They also added back the patients' T cells after the transplant because these cells also promote acceptance of blood-forming cells, but don't increase rates of graft-versus-host-disease (GVHD).

The authors transplanted parental stem cells into 19 patients (mean age 13.1 years) who had frequent or severe SCD symptoms.

Engraftment, where the recipient's body accepts the new stem cells and they begin to produce new blood and immune cells, occurred in all 19 patients, while chimerism, which is a measure of the durability of engraftment, was at a 97% rate 1 year after transplant.

One patient developed GVHD disease within 100 days of transplant, while another developed it >100 days post-transplant.

In follow-up testing 2 years after the transplant, patients had improved heart and lung function, no evidence of stroke or inflammation of blood vessels, and improved or stable intellectual functioning, memory, language, and executive function.

Physical and emotional quality of life were also significantly improved at 2 years.

After 3 years of follow-up, "there are no patients who have signs of sickle cell disease, or sickle symptoms, and they are all off immunosuppressive therapy, and off all other drugs," Cairo stated.

Most importantly, patients with high-risk SCD features who have a living parent "now have a potential allogeneic donor in the family," he added.

In a second study, a novel approach to gene therapy showed promise in helping patients stop producing sickle hemoglobin and produce fetal hemoglobin instead, reported Erica Esrick, MD, of Boston Children's Hospital, and colleagues.

Fetal hemoglobin inhibits the development sickle hemoglobin polymers, Esrick explained.

Esrick's group targeted a protein called BCL11A. has shown that silencing BCL11A can reactivate fetal hemoglobin production, effectively reversing SCD.

The technique, devised by co-author David Williams, MD, also of Boston Children's Hospital, involves the use of a lentiviral vector in a patient's own stem cells to reintroduce the capacity to make fetal hemoglobin.

Four patients enrolled in the pilot study, one of who has already received gene therapy. Prior to transplant, that patient required monthly transfusions to alleviate SCD symptoms, but post-study, required one transplant in the following 6 months, according to Esrick.

In addition, while blood tests show high levels of fetal hemoglobin in this patient, and he has not experienced any of the complications associated with SCD, such as pain, anemia, and respiratory or neurological events.

"Targeting BCL11A using gene therapy looks to be a promising approach to increase fetal hemoglobin," Esrick stated.