Sickle cell disorder is a genetic blood condition where red blood cells become rigid and take on a sickle shape, causing blockages in blood vessels. This can lead to severe pain, fatigue, infections, and other complications. It's inherited when both parents pass on a specific gene mutation. Current treatments focus on managing symptoms and preventing complications, such as pain management, blood transfusions, and medication. Early detection and comprehensive medical care are crucial for improving quality of life for those with sickle cell disorder.

Anyone who has severe sickle cell disorder and has a relative that is willing and able to be a stem cell donor. However, as is common with all clinical research studies, for safety and to comply with the research protocol, teams will have to complete screening tests and checks to confirm that an individual is suitable for the study.

Severity will be decided by the individual’s sickle doctor. There is an understanding across the board amongst sickle doctors about what the criteria are for severe sickle cell disorder. This is based on previous research studies in sickle. Some characteristics of an individual with “severe” sickle include:

- Regular blood transfusions in the past year

- Regular pain crises (2 or more) in the past two years

- Previous sickle related stroke

- Regular chest problems in the previous two years

- Those that need hydroxycarbamide or blood transfusions but cannot tolerate this treatment due to side effects.

- People with organ damage related to sickle

- High risk of dying from sickle related complications

Inclusion is based on severity and not on SS or SC type. If an individual is considered to have severe sickle cell, then that is enough to be considered for the study.

A bone marrow or stem cell transplant is a medical procedure used to treat certain diseases, including some types of cancer and genetic blood disorders like sickle cell disease. During the transplant, damaged or diseased bone marrow (the soft, spongy tissue inside bones where blood cells are produced) is replaced with healthy stem cells. These stem cells can come from a donor (allogeneic transplant) or from the patient themselves (autologous transplant), collected before undergoing chemotherapy or radiation therapy. The goal of the transplant is to replenish the body's supply of healthy blood-forming cells, which can help restore normal blood cell production and function. This procedure can be complex and carries risks, but it can offer a chance for a cure or significant improvement in the patient's condition.

A "haplo-identical" stem cell donor refers to a type of stem cell transplant where the donor is a genetic "half-match" for the person receiving the stem cells. This often happens within families, like a sibling, parent or child donating to another family member.

Your body has certain genetic markers called HLA markers that help your immune system recognise what belongs in your body and what doesn't. A "haplo-identical" stem cell donor is someone who shares only half of these markers with you. Usually, doctors look for donors who match all these markers, a “full-match”, but sometimes it's hard to find a perfect match. So, even if the donor is only a half-match, doctors can still use their stem cells for a transplant. They use special techniques to make sure your body accepts these new cells and doesn't attack them. This way, more people can get the treatment they need, especially when finding a perfect match proves difficult.

This study is available to those over the age of 18. There is no upper age limit.

- Anyone who does not have sickle cell disorder

- Anyone who already has a “full-matched” sibling donor

- Anyone who has had a bone marrow/stem cell transplant before

- Anyone who is pregnant or breastfeeding

- Anyone with SCD that is capable of having children but are not willing to use contraception

- Anyone who has antibodies against their donor’s blood type

- If someone has HIV or active hepatitis B or C infection

- Anyone with an uncontrolled bacterial, fungal or viral infection

- If someone is already participating in another trial or has participated in the previous 3 months

- Anyone who is not well enough to go through the transplant procedure.

Randomisation is the process of assigning participants in a clinical trial to different treatment groups randomly, like at a flip of a coin. Often this process is carried out by a computer. This ensures each participant has an equal chance of being in any group. This helps to reduce bias, ensuring that any differences in outcomes between groups are due to the treatments being compared. Treatment allocation refers to the actual assignment of participants to specific treatment groups based on this randomisation process. These principles are vital for maintaining the validity and reliability of clinical trial results, guiding clinical decision-making, and improving patient care.

A control or comparator group is essential in clinical trials because it helps researchers determine if a new treatment is actually safe and effective. By comparing the group receiving the new treatment to a control group that does not, researchers can see if any differences in outcomes are due to the treatment itself. This comparison helps establish a clear baseline to compare against the treatment group, minimise bias, and ensures that the results are reliable, ultimately helping to advance medical knowledge and improve medical care.

In REDRESS, standard care refers to the best available approved treatments for sickle cell. This  includes transfusions or medicines such as hydroxycarbamide and voxelotor. If any other new treatments are approved while this study is ongoing, then this will also be available for participants in the study.

Chemotherapy is usually a treatment to fight cancer that uses strong medications to kill fast-growing cells. In the context of a stem cell transplant, high doses of chemotherapy are given just before the transplant to wipe out the patient's diseased bone marrow, making space for the new stem cells to grow and start producing healthy blood cells. This step is essential for ensuring that the transplanted stem cells can take hold and start producing healthy blood cells.

Additionally, chemotherapy also helps to lower the patient's immune system, which is important for two reasons. It reduces the risk of rejection when the patient is receiving stem cells from a donor. Also, it helps to prevent a condition called Graft Versus Host Disease (GvHD), where the donor's immune cells attack the recipient's body. So, while chemotherapy can be a challenge because of its side effects, it's a vital part of the stem cell transplant process, helping to give the new stem cells the best chance of success in treating the disease. Participants will have the opportunity to ask more questions and find out more about the effects of chemotherapy before deciding to participate.

All risks will be discussed with each individual as part of the informed consent process. It is important that those wishing to participate consult with their sickle doctor before deciding to take part in this research.

Stem cell transplants, mainly considered for severe sickle cell disorder (SCD), carry significant risks. Early side effects include pain, nausea, and diarrhoea due to the conditioning treatment before the transplant. This treatment can also affect various body parts like the lungs, liver, and heart. Additionally, there's a heightened risk of infections, especially bacterial, after the transplant, which requires immediate antibiotic treatment. Graft Versus Host Disease (GvHD) is another concern where the donor's immune system may attack the recipient's body cells, leading to skin rashes, diarrhoea, or liver issues. To prevent GvHD, special treatments like post-transplant cyclophosphamide are used.

Longer-term risks include infertility in both males and females, requiring fertility preservation options before the transplant. There's also a heightened risk of developing secondary cancers due to treatments like chemotherapy and radiation. While the transplant can 'cure' SCD, it may not fully reverse previous damage caused by the disease, necessitating ongoing follow-up for complications. Additionally, there's a possibility of rejection where the bone marrow graft is rejected, leading to a relapse of SCD. Despite these risks, bone marrow transplants remain a crucial treatment option for severe cases of SCD, with medical teams closely monitoring patients for any complications.

There may be other risks not covered above, and those which would be specific to the individual. The  medical team will go through these thoroughly with each participant prior to transplant. Individuals will have the opportunity to ask any questions they have. Participants must give their consent before any procedures take place. Individuals can also change their mind about having the treatment prior to undergoing the transplant.  

Yes, it is often recommended to see a fertility specialist to preserve eggs or sperm before undergoing a stem cell transplant. This is because the chemotherapy and radiation used in the transplant process can affect fertility. A fertility specialist can provide options such as egg or sperm freezing to help preserve the ability to have biological children in the future. Participant will have the opportunity to discuss this with their healthcare team as part of the treatment planning.

The length of time in hospital for someone undergoing a stem cell transplant can vary depending on several factors, including the type of transplant, the individual's overall health, and any complications that may arise during the procedure or recovery. Before the transplant, for about 10 days, they will get chemotherapy to prepare the body for the procedure. The process of the stem cell transplant itself takes place over the course of one day. Stem cells will be taken from the family donor and infused into the recipient on the same day.  After the transplant, the individual will need to stay in the hospital for approximately 3-6 weeks because the patient's immune system needs time to recover and adjust to the donor cells, and there is a higher risk of complications and infections. This time in hospital is for close monitoring and recovery.

After discharge from the hospital, patients will still need to come back for close monitoring and follow-up care, including regular check-ups, blood tests, and sometimes additional treatments to manage complications or support recovery. Overall, the duration of hospitalisation and recovery can vary from person to person, and it's important for patients to work closely with their healthcare team to understand and navigate their individual treatment plan and recovery process.

Stem cell transplant can affect both home and work life in various ways. At home, individuals may experience fatigue and physical limitations, needing help with daily tasks. After a person has had transplant, they may not be able to go out frequently to reduce the risk of picking up infections from outside. At work, individuals may need time off to recover, perhaps needing a phased return to work. Participants will need to discuss this further with their doctor as this may be different for each person.

Patients undergoing a stem cell transplant receive extensive support throughout the process. Before the transplant, they get medical evaluations, counselling, and help with fertility preservation. During the transplant, they are closely monitored by a medical team, receive emotional support, and get nutritional advice. After the transplant, patients have regular follow-up appointments, access to rehabilitation services, and ongoing counselling and support groups to help them adjust and recover. Support is also provided to caregivers to help them manage their roles effectively.

A close relative of a person with sickle cell may be eligible as a donor such as siblings or half-siblings, parents, grown-up children, aunts, uncles, or cousins. A relative can have sickle cell trait and still be eligible as a donor.

Stem cell donors usually do not need to stay in the hospital overnight but it depends on the type of donation. For bone marrow donation (the usual process for this study), the procedure is typically done in a hospital under anaesthesia. Bone marrow is extracted from the pelvic bone using a needle. While most donors are discharged on the same day after a few hours of recovery, some may need to stay overnight for observation if the doctors think it’s necessary as a precaution. Donors usually experience some discomfort and fatigue but can resume normal activities within a few days to a week.

For peripheral blood stem cell (PBSC) donation, the process is done on an outpatient basis. Donors receive medication for several days before the donation to increase stem cells in their blood. The actual donation, called apheresis, involves drawing blood from one arm, separating out the stem cells, and returning the rest of the blood to the other arm. This takes about 4-6 hours and donors can go home the same day.

There are some risks associated with being a donor, but these are all associated with the donation procedure itself. Not with participating on the study. For bone marrow donation, the donor may experience pain and soreness in the hip and lower back, and there's a small risk from the anaesthesia. For peripheral blood stem cell (PBSC) donation, the donor may have side effects from medication used to increase stem cells, such as bone pain and headaches, and the donation process itself can cause light-headedness or chills. There's also a minor risk of infection and bleeding at needle sites. Most donors recover fully within a few weeks, and serious complications are rare. These are discussed with the donor by the clinical teams. More information on stem cell donation can be found on here: www.bbmr.co.uk/donating-stem-cells

There is no cost to participants on the trial for treatment. The average cost of a transplant via private healthcare is approximately. £200,000. However, exact sums are difficult to confirm, and this figure is only a guide, not an exact quote.

If someone is already taking part in another study testing different unapproved therapies for their sickle, they can't be part of this study. However, if the research does not involve any sickle cell related interventions or medicines, they could still be eligible. Individuals will need to discuss this with their doctor’s or the research team to confirm.

Participants will be in the study for a total of 2 years. At a minimum this will involve initial screening and baseline visits then, depending on the group the individual is randomised to, preparation and admission for transplant with regular visits until 3 months post-transplant. Participants will then have set study visits to collect primary outcome data after 6 months, 12 months and 24 months post-randomisation. These visits will be scheduled at the same time as standard hospital visits as much as possible. The research team will also ask participants about their quality of life and use of healthcare resources at 3 monthly intervals, either in person or over the phone.

You can contact the REDRESS team via email at: redress@kcl.ac.uk

If you have sickle cell, you can discuss this further with your GP or sickle consultant doctor.

You can also find a study site near you and contact a local research team member by visiting the “Find a study site” webpage.