Health Editor’s Note: Sickle cell disease is a collection of red blood cells disorders that are inherited.  Most people with sickle cell disease in the U.S. are of African American ancestry, but this condition is also common in the Hispanic genetic pool.

Red blood cells (RBCs) are normally of an oval shape that allows for them to flow/slide freely within the veins and arteries of the body.  In sickle cell disease, the RBCs are in the shape of a sickle or crescent with sharper edges.  This shape does not allow for smooth negotiation and fit within the blood vessels and often the cells will become “stuck” and cause a disruption in the free flow of blood. The walls of the RBCs are more fragile and can be broken down more easily which leads to increased hemoglobin in the system. 

Early symptoms and signs include swelling of feet and hands, and symptoms of anemia which include feeling tiredness and jaundice (yellowing of the skin/eyes). Eventually sickle cell disease will cause delayed growth and periods of pain. For children, there will usually not be pain between the crises, but for adults and adolescents there may be ongoing pain due to decreased oxygen delivered to tissues with the potential for harm to brain, eyes, lungs, liver, heart, spleen, kidneys, bones, joints, and skin. 

Sickle cell disease is a negative life changer for anyone who has it.  New types of stem cell transplantation and gene therapy may now be able to stop this disease…..Carol 

Studies Explore Possibility of Parent Donor; Boosting Fetal Hemoglobin Production

By Mike Bassett, Contributing Writer for MedPage Today

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. Previous research 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.

Cairo disclosed a relevant relationship with Janssen. Co-authors disclosed multiple relevant relationships with industry.

Esrick and many co-authors disclosed relevant relationships with Bluebird Bio. Some co-authors are company employees.

Primary Source
American Society of Hematology
Source Reference: Cairo M, et al “Significantly improved long term health related quality of life (HRQL) and neurocognition rollowing familial haploidentical stem cell transplantation (HISCT) utilizing CD34 enrichment and mononuclear (CD3) addback in high risk patients with sickle cell disease (SCD)” ASH 2018; Abstract 162

Secondary Source
American Society of Hematology
Source Reference: Esrick E, et al “Flipping the switch: Initial results of genetic targeting of fetal to adult globin switch in sickle cell patients” ASH 2018; Abstract 1023