Senior Consultant, Bone Marrow Transplant & Haemato-Oncology, BLK-Max Super Speciality Hospital, New Delhi
Part 10 of 11 in Diagnosis and Management of Sickle Cell Disease
Bone Marrow Transplant and Gene Therapy: Curing Sickle Cell Disease
November 24, 2024
Bone marrow transplant is currently the only curative option for sickle cell disease. The first major study of parents' decisions around transplant was published in the New England Journal of Medicine in 1991: parents were given a detailed description of what the transplant would involve, including its complications, and then presented with a series of hypothetical scenarios asking what percentage risk of mortality they would accept in order to obtain a cure for their child.
Donor Types and Survival Data
Transplant can be performed using a matched sibling donor, a matched unrelated donor, or an HLA-haploidentical donor. Data pooled from three transplant registries covering more than a thousand matched sibling transplants performed between 1986 and 2013 showed a five-year overall survival of 95% for children under 16, and around 81% for those transplanted after age 15; using a reduced-intensity conditioning regimen produced an overall survival of 93%. The advent of haploidentical stem cell transplant in particular has changed the calculus for many families, since donor availability is no longer limited to a matched sibling and outcomes have become good enough that more families are willing to pursue transplant.
Who Qualifies for Transplant
Indications for bone marrow transplant include irreversible end-organ damage, a stroke, an elevated tricuspid regurgitant velocity, sickle kidney disease, sickle hepatopathy, two or more vaso-occlusive crises requiring hospitalisation in a year, or a single episode of chest syndrome occurring while the patient is already on hydroxyurea. There is no strict upper age limit for transplant, since it can be performed in adults as well as children, but the risk rises and outcomes are not as good with increasing age, partly because the major organs are more likely to already be affected by the disease by then, which can itself reduce eligibility.
Gene Therapy: A Second Curative Route
Gene therapy is the other transformative curative option, approved by the FDA in December 2023 for children over 12 years of age, in both a gene addition and a gene editing form. The process resembles an autologous stem cell transplant: the patient's own haematopoietic stem cells are collected and sent for gene addition or gene editing, and after the patient receives myeloablative conditioning, usually with busulfan, the modified cells are transfused back. Once these genetically modified stem cells engraft, the patient is cured. The main barriers to gene therapy are its prohibitively high cost, the loss of fertility and the risk of secondary malignancies that come with the chemotherapy conditioning it requires.
What Bone Marrow Transplant Costs
Cost depends heavily on the type of donor available. For a matched sibling donor, transplant costs in the range of 20,000 to 24,000 US dollars; for a haploidentical, half-matched transplant where no matched sibling is available, the cost is higher, reported at different points in the session as roughly 35,000 to 45,000 US dollars depending on the specific case.
This article is based on a Jivo Masterclass session conducted by Dr. Divya Doval, Senior Consultant, Bone Marrow Transplant & Haemato-Oncology, BLK-Max Super Speciality Hospital, New Delhi. The article has been summarised with the assistance of an AI tool from the original masterclass recording. Watch the full Masterclass recording
This guide is based on a live Jivo Masterclass: Dr. Divya Doval taught doctors across Africa on November 24, 2024.
FROM THE LIVE Q&A
Moderator
Under what age is stem cell transplant effective?
Dr. Divya Doval
There is no age limit. We have transplanted adults as well. The risk simply increases with age and the outcomes are not as good, but otherwise transplant can be done at any age if the organ systems are fine. With age, the risk of stroke and of the liver and kidneys being affected increases, which then reduces eligibility for transplant.
Frequently Asked Questions
What is the overall cost of bone marrow transplant at your facility?▼
If it's a matched sibling donor, an HLA-matched sibling, it is somewhere between 20,000 and 24,000 US dollars. If a matched sibling is not present and it is a half-match transplant, the price goes up to around 35,000.
What is the role of urine alkalisation in the management of vaso-occlusive crisis?▼
Alkalinisation of the urine prevents acidosis and infections, and once the urine is alkaline, crystallisation is prevented as well. Overall, it helps with the pain.
What is the management of sickle cell disease in pregnancy?▼
Once a patient is pregnant, hydroxyurea cannot be given for the first three months, which can be challenging, so we make sure the patient is well hydrated and stays warm, and we try to prevent all sorts of crisis through the pregnancy. In the second and third trimester, one can start hydroxyurea if required, and transfusions can be done if needed. Morbidity and mortality are high, and every patient should be counselled before starting a family that the risks for both mother and baby are high, since a crisis during labour or childbirth can be quite difficult to manage.
What is the symptomatic treatment for chronic jaundice in sickle cell disease, especially in children who have never had a blood transfusion?▼
This jaundice happens because the red blood cells are breaking down. It is chronic, and these red cells will keep breaking, so a lot of patients will have a high bilirubin, but there isn't a specific treatment for the jaundice itself. We can reduce the underlying haemolysis by starting hydroxyurea, but the jaundice itself does not otherwise affect most patients. If there is chronic jaundice, we do need to find the cause by checking for hepatitis B and C and other infective causes, to make sure it isn't due to something else.
From an epidemiological point of view, what makes Africa more affected than other countries in the world?▼
I think the whole geographical distribution is just a genetic basis. A certain gene pool has that gene mutation, so depending on the geographical area, that population is more susceptible to carrying the mutation and having the disease.
In This Series: Diagnosis and Management of Sickle Cell Disease
- 1.Diagnosis and Management of Sickle Cell Disease
- 2.Sickle Cell Disease Explained: Inheritance, Haemoglobin S and Why Cells Sickle
- 3.Diagnosing Sickle Cell Disease: From Newborn Screening to Confirmatory Testing
- 4.Pain Crisis and Acute Chest Syndrome: The Two Most Common Sickle Cell Emergencies
- 5.Stroke Risk in Sickle Cell Disease: Screening and Preventing a Devastating Complication
- 6.How Sickle Cell Disease Damages the Spleen, Liver, Kidneys and Eyes
- 7.Priapism, Infections and Aplastic Crisis in Sickle Cell Disease
- 8.Hydroxyurea and Newer Drug Therapies for Sickle Cell Disease
- 9.Blood Transfusion and Iron Overload Management in Sickle Cell Disease
- 10.Bone Marrow Transplant and Gene Therapy: Curing Sickle Cell Disease
- 11.Sickle Cell Disease and Pregnancy: Managing a High-Risk Combination