Bone Marrow Donors for Sickle Cell Patients From Africa

Finding a bone marrow donor usually decides whether a sickle cell patient from Africa can have a transplant. A fully matched sibling is the best donor, but only about a quarter of patients have one. Unrelated donor registries rarely help, because African populations are under-represented in them. Dr. Vikas Dua's answer is a half-matched (haploidentical) transplant from a parent, which still offers an 85 to 90% chance of cure.

This article follows the donor search in the order a referring doctor should work through it: HLA typing, the sibling donor, the registry gap, the parent as donor, and the place of cord blood. The wider picture of sickle cell transplant is in the sickle cell anaemia bone marrow transplant guide.

HLA typing: the test that decides the donor

Every allogeneic transplant starts with HLA typing. Human leukocyte antigens (HLA) are proteins on the surface of most cells that the immune system uses to tell "self" from "foreign". The closer the match between donor and patient, the lower the risk that the patient rejects the graft, or that the donor's immune cells attack the patient's body (graft-versus-host disease).

The process is simple to describe. The laboratory types the patient and each brother and sister, and the results show whether any sibling is a full match. When a doctor from DR Congo asked during the session what criteria should be used to choose a donor within the family, Dr. Dua's answer was exactly this: type the patient and the siblings, and the HLA results will tell you whether a full match exists in the family.

Precision matters. High-resolution HLA typing identifies the specific variants of each HLA gene, rather than broad groups, and is the standard for selecting a transplant donor. Fortis Memorial Research Institute, Gurgaon, India, where Dr. Vikas Dua is Principal Director & Head - Pediatric Hematology, Hemato Oncology & Bone Marrow Transplant, performs high-resolution HLA typing in-house.

Why a matched sibling is the best donor

A brother or sister who shares the same two sets of HLA genes as the patient is the ideal donor. Dr. Dua puts the chance that a given patient has a fully matched sibling at 25 to 30%. Put another way: of 100 patients who need a transplant and have siblings, 25 to 30 will be lucky enough to have a full-match donor in the family.

The reason is genetic. Each child inherits one set of HLA genes from each parent, so any one brother or sister has a one-in-four chance of inheriting exactly the same combination. Families with several children have better odds, which is why every full sibling should be typed.

A matched sibling transplant gives the best results available: Dr. Dua puts the chance of cure at 90 to 95%. The full outcome data are in the article on sickle cell transplant cure rates by donor, age and regimen.

Why unrelated donor registries rarely help patients from Africa

Unrelated donor registries rarely find a match for patients from Africa, because African populations are under-represented in them. When no sibling matches, the next option in most of the world is a matched unrelated donor: a volunteer with the same HLA type, found through a donor registry. Registries list millions of volunteers whose HLA types have already been recorded. Dr. Dua noted that the largest registry in the world is in Germany and the second largest is in the US, with many others in other regions.

This is where patients from Africa face a structural disadvantage. Africa has very few unrelated donor registries: South Africa runs the continent's established national registry, and most countries have none. As Dr. Dua explained, if a population does not have its own registry, the chance of finding a full-match unrelated donor in other registries is low. People of African ancestry also have the greatest HLA diversity of any population, which makes a match harder to find even in a large registry.

Asked by a doctor whether the gap reflects a shortage of specialists, Dr. Dua said that is one of the reasons: transplants are not widely performed in Africa outside South Africa, although he noted that some transplants are being done in Benin City, Nigeria. His challenge to the doctors on the call was direct. African clinicians need to come together and build their own registry, so that a patient who needs stem cells can find a donor from his or her own population.

India has its own unrelated donor registry, DATRI. For a patient from Africa, though, the practical consequence is clear: if there is no full match in the family, waiting for an unrelated donor is rarely a realistic plan.

Haploidentical transplant: can a parent donate bone marrow?

The answer to the registry gap is already in the family. Every child receives 50% of his or her genes from the father and 50% from the mother, so each parent is at least a half match. A transplant from a half-matched donor is called a haploidentical transplant.

Dr. Dua was emphatic on this point: even if a patient has no full-match donor inside or outside the family, a transplant can still be done, with good outcomes, by taking the father or mother as the donor. Half-matched transplants for sickle cell disease have produced very good outcomes at St. Jude Children's Research Hospital in the US, and he puts the chance of cure at 85 to 90%. That is a few percentage points below a matched sibling transplant, and a decisive improvement on staying without a curative option.

A doctor who refers patients from Nigeria raised the practical worry directly: if patients are referred and arrive without a match, the journey is wasted. Dr. Dua's response was to plan for the haploidentical option from the start. Parents should travel with the patient, so that a donor is available on arrival if no sibling matches. Asked to confirm that parents should travel with the patient, he answered: "Undoubtedly, my friend."

Cord blood transplant for sickle cell: public and private banks

Cord blood is the third source of stem cells. When a baby is born, blood rich in stem cells can be collected from the placental side of the umbilical cord.

The cells go to one of two kinds of bank:

• A private bank, where the family pays to store the unit so that it can be used later for the same child or a sibling if the need arises.
• A public bank, where the donated unit is available to anyone. When a patient needs a transplant, HLA typing shows whether a stored unit matches, and a matching unit can go to any patient in need.

Collection can be done at any birth, for any future indication, not only in families affected by sickle cell disease.

The history is relatively recent. The first successful cord blood transplant was performed in France in 1988, for a patient with Fanconi anaemia, an inherited bone marrow failure syndrome. The first public cord blood bank was established in New York in 1992. Data from the US national donor registry show cord blood and other alternative-donor transplants rising year by year.

Practice in India, however, favours adult donors. Answering a question from the session, Dr. Dua said that cord blood transplants are not preferred in India because of the number of issues associated with them, and that an adult donor transplant is chosen over a cord blood unit. A single cord blood unit contains a limited number of stem cells, so blood counts recover more slowly after transplant than with an adult donor.

How stem cells are collected from the donor

Once the donor is chosen, the stem cells can be collected from the bone marrow or from the peripheral blood. With peripheral blood collection, the donor sits in the blood bank while a machine draws blood, separates out the stem cells and returns the rest. Dr. Dua stresses that it is safe for the donor: the growth-factor injections given beforehand commonly cause temporary bone aches, but serious complications are rare. That reassurance matters most when the donor is a parent who has travelled with a sick child.

The cells are collected into sterile bags, and the team checks in-house that a sufficient stem cell dose has been obtained. If they will be used later, they can be cryopreserved (frozen) in the hospital.

Bone marrow donor pathway for sickle cell patients from Africa

Dr. Dua's answers across the session add up to a clear sequence for doctors referring a patient with sickle cell anaemia:

1. Confirm the indication. Stroke, acute chest syndrome, frequent pain crises, or complications despite hydroxyurea make a patient a transplant candidate.
2. Type the patient and every full sibling with HLA typing. There is a 25 to 30% chance that a sibling is a full match.
3. If a sibling matches, plan a matched sibling donor transplant, with a 90 to 95% chance of cure.
4. If no sibling matches, do not wait for an unrelated donor. Plan a haploidentical transplant with the father or mother as donor, with an 85 to 90% chance of cure.
5. Ask the parents to travel with the patient, so that a donor is in place on arrival.
6. Refer early. Outcomes are best when transplant is done in childhood.

Cost depends on the donor type. At the time of the session, Dr. Dua put a matched sibling transplant at roughly US$25,000 and a half-matched transplant at around US$35,000, before about US$10,000 for accommodation and logistics. Current ranges are on the haploidentical (half-match) bone marrow transplant cost page.

The doctors' questions on donor banks, registries and referral are answered in full on the masterclass Live Discussion page, and more on Dr. Dua's practice is on his doctor profile.