Sickle Cell Transplant Cure Rates by Donor, Age and Regimen

The cure rate of a bone marrow transplant for sickle cell anaemia is 90 to 95% when the donor is a matched sibling, according to Dr. Vikas Dua of Fortis Memorial Research Institute, Gurgaon. With a half-matched parent as donor, the cure rate is 85 to 90%. Age at transplant matters as much as donor type: outcomes are around 95% before the age of 16 and around 80% after it.

Those three numbers, and the evidence behind them, are what families and referring doctors weigh when deciding whether and when to proceed. This article explains each, then turns to the conditioning regimen, fertility, mixed chimerism and the first year after transplant. The overview of the disease and the transplant pathway is in the sickle cell anaemia bone marrow transplant guide.

Sickle cell transplant cure rates with a matched sibling donor

A matched sibling donor transplant offers a 90 to 95% chance of cure. Dr. Vikas Dua, Principal Director & Head - Pediatric Hematology, Hemato Oncology & Bone Marrow Transplant, Fortis Memorial Research Institute, Gurgaon, India, told the masterclass that his centre's results are comparable to those reported from centres in the US, Belgium and France.

The published evidence he presented supports that range:

• A 2007 study of long-term results after myeloablative transplant showed cure rates of more than 90% with a conditioning regimen of busulfan, cyclophosphamide and antithymocyte globulin (ATG).
• St. Jude Children's Research Hospital in the US has reported similar outcomes, with more than a 90% chance of cure.
• A 2017 publication on 1,000 recipients of matched sibling transplants for sickle cell anaemia, performed between 1986 and 2013, reported five-year overall survival of about 93%, with higher mortality in older patients.

Overall survival and cure are not the same measure. Overall survival counts every patient alive after transplant; cure counts those who are alive and free of sickle cell disease, which excludes patients whose graft failed and whose own sickle marrow returned. The two figures sit close together in matched sibling transplant, which is why the outcomes are described as very good. Dr. Dua's centre had performed more than 150 transplants for sickle cell anaemia at the time of the session.

Haploidentical transplant cure rates: a parent as donor

Most patients do not have a matched sibling. For them, a haploidentical transplant uses the father or mother, who always share half their HLA genes with the child, as the donor. Dr. Dua puts the chance of cure at 85 to 90%, and cited very good half-match outcomes from St. Jude Children's Research Hospital. The message he wants every family and every doctor to understand: even without a full match inside or outside the family, a transplant can be done with good outcomes.

This matters disproportionately for patients from Africa, where unrelated donor registries are scarce. How the donor is chosen, and why parents should travel with the patient, is covered in bone marrow donors for sickle cell patients from Africa.

Best age for a sickle cell transplant: before 16

The data Dr. Dua presented show a clear threshold. Transplant before the age of 16 gives outcomes of around 95%; after 16, outcomes fall to around 80%. His advice to families is consistent: transplant early.

The reasoning is as much clinical as statistical. Every year of sickle cell disease adds pain crises and accumulated damage to the brain, lungs, kidneys, eyes and bones. A patient who is not offered a transplant will keep suffering, and at some point the organ damage makes even a transplant too risky to perform. "Sooner the better" is his summary.

There is no absolute age cut-off. Asked by a doctor from DR Congo whether an age limit exists, Dr. Dua said his centre has also transplanted adults, and that its oldest sickle cell recipient was 34 at transplant and doing well. The lower figure after 16 is a reason to act early, not a reason to refuse an older patient.

The conditioning regimen: busulfan, cyclophosphamide and ATG

Conditioning is the chemotherapy given in the days before the stem cell infusion. It has two jobs: to clear the patient's own marrow, which produces the sickle cells, and to suppress the immune system enough that it does not reject the donor's cells.

The regimen behind the strongest long-term results in matched sibling transplant combines three drugs:

• Busulfan, an alkylating chemotherapy drug that eliminates the existing marrow
• Cyclophosphamide, which adds to the marrow-clearing effect and suppresses the immune system
• Antithymocyte globulin (ATG), an antibody preparation that depletes the patient's T cells, the immune cells most responsible for rejecting a graft

Dr. Dua singles out ATG as a very important component. In the French national series, adding ATG to conditioning cut graft rejection from about 23% to 3%, and event-free survival in patients transplanted after its introduction reached 95%, so his practice is to include it as part of the conditioning regimen when doing a transplant.

A regimen that destroys the patient's marrow completely is called myeloablative. It gives durable engraftment, but its toxicity includes a risk to fertility.

Non-myeloablative conditioning and fertility after transplant

Families who travel for transplant are, in Dr. Dua's experience, consistently worried about long-term side effects, infertility in particular. His response is that changes in conditioning have reduced that risk, and that similar outcomes can be achieved with slightly different conditioning regimens.

Non-myeloablative and reduced-intensity conditioning use lower doses of chemotherapy that suppress the marrow and immune system without destroying the marrow completely. Dr. Dua's point is that a very heavy dose of chemotherapy is not needed every time: good transplant outcomes can be achieved with less intensive chemotherapy. The advantages he listed are fewer toxic effects, a lower chance of infertility, and a better prospect of patients preserving their fertility.

Reduced-intensity regimens lower the risk of infertility but do not remove it entirely, and fertility counselling before conditioning is standard practice in transplant medicine. The choice of regimen is made by the transplant team for each patient.

Mixed chimerism: a partial graft can still cure

After transplant, the blood is tested to measure what proportion of cells come from the donor and what proportion from the patient. When all the blood cells are the donor's, this is full donor chimerism; when both populations coexist, it is mixed chimerism.

Families sometimes assume that anything short of 100% donor cells means the transplant has failed. Dr. Dua was clear that this is not so in sickle cell disease. Even with some donor cells and some of the patient's own cells, the transplant remains successful, and the patient can lead a good, healthy life. Full donor chimerism is not required for a good outcome. The reason is that the donor's healthy red cells survive far longer in the circulation than sickle cells, so a partial graft can still keep the disease under control.

This finding also helps explain why reduced-intensity conditioning works: it does not need to eliminate every one of the patient's own marrow cells to cure the disease.

How long is immunosuppression needed after transplant?

Dr. Dua's team usually stops all immunosuppression one year after transplant, and only 10 to 15% of patients need it for longer. He gave these figures when a doctor asked during the session how long children stay on the medicines. Immunosuppressive medicines prevent graft-versus-host disease (GVHD), in which the donor's immune cells attack the patient's tissues, and protect the graft. Prolonged immunosuppression is typically needed by patients who develop chronic GVHD.

The initial stay for treatment is about three months; immunosuppression then continues until about one year after transplant.

What the numbers mean for a family deciding now

Read together, the data give families a straightforward frame:

1. A cure is realistic. With a matched sibling, 90 to 95%; with a parent, 85 to 90%.
2. Delay costs more than it saves. Outcomes fall from around 95% before 16 to around 80% after.
3. The lack of a sibling match is not a dead end. A haploidentical transplant from a parent can still be done with good outcomes.
4. Long-term effects are being reduced. Conditioning regimens have changed, and infertility risk is lower with non-myeloablative approaches.
5. Treatment ends. Most patients stop immunosuppression one year after transplant.

At the time of the session, Dr. Dua put the cost of a matched sibling transplant at roughly US$25,000 and a half-matched transplant at around US$35,000, plus about US$10,000 for accommodation and logistics, with a stay of about three months. Current ranges are on the matched sibling donor bone marrow transplant cost page.

Doctors' questions on age limits, cost and immunosuppression are answered in full on the masterclass Live Discussion page, and more on Dr. Dua is on his doctor profile.