Cord Blood Transplants for Sickle Cell Disease
Sickle Cell Disease (SCD) is an inherited disease of red blood cells caused by a gene mutation involving a single amino acid substitution in the hemoglobin gene. The red blood cells become sickle shaped (see figure below) under stress conditions, leading the cells to stick together and block tiny blood vessels. This can cause pain crises, stroke, and chronic progressive organ damage.
SCD is the commonest inherited disorder in the African-American population. It is estimated that there are close to 100,000 people with SCD in the United States and over 2 million worldwide, mostly in Africa, the Middle East, and India.
The clinical manifestations of SCD can vary from patient to patient, but 10-25% of patients have the severe form of the disease with recurrent episodes of pain crises, recurrent acute chest syndrome, stroke in childhood, and other significant clinical manifestations.
Although over 90% of children born with SCD will survive to adulthood in the US, ongoing organ damage results in a steep rise in mortality in early adulthood such that the median survival for a patient with SCD in the US is in the 40’s, almost half that of an unaffected healthy sibling. The prognosis for children born in the developing world is much worse, with the vast majority of children who have SCD dying in childhood, mostly resulting from poor access to comprehensive and quality medical care.
Currently the only curative therapy for SCD is a transplant with blood-forming (hematopoietic) stem cells from a healthy donor. The source of the stem cells can be bone marrow, peripheral blood stem cells, or umbilical cord blood.
Stem cell transplants are increasingly being considered for children and young adults with the severe form of SCD. The results are excellent when the stem cell donor is a matched sibling: less than 5% mortality, 5-10% incidence of graft rejection, and close to 90% SCD-free survival.
After a successful stem cell transplant, SCD patients become symptom-free and can expect to live a very good quality of life. The possible complications of the transplant are: reproductive organ damage, sterility, and perhaps a chronic immune reaction between the cells of the donor and the patient that is called graft-versus-host disease and occurs in about 10-20% of transplant patients today.
When a family has one child with SCD and another who is unaffected, they have the opportunity for the healthy sibling to serve as a stem cell donor for the SCD patient. Thus far, transplants with matched sibling cord blood seem to be just as good as matched sibling bone marrow. Some families may transplant both cord blood and bone marrow from the same donor sibling, in the event that the stem cell count of the stored cord blood is low.
Expectant mothers who have a child with SCD should be counseled and informed about the importance of saving their baby’s cord blood for potential transplant of the child with SCD. Since SCD is recessively inherited, there is a 25% chance that the unborn baby may also have SCD, and a 25% chance that he/she will be a tissue-type match to the SCD patient. A number of both public and private cord blood banks offer free storage to families with medical needs like SCD.
Because not all patients have matched sibling donors, researchers have resorted to transplanting SCD patients with unrelated donors found on registries like Be The Match or Be The Cure. These results are not as good as related donors, because of increased complications due to tissue type incompatibility between the donor and recipient. Newer approaches to transplantation are now being explored in several clinical trials for children and adults with SCD who lack matched sibling donors.
SCD patients and parents of children with SCD should know about the ability of stem cell transplants to cure this affliction. They need to be educated and empowered to make decisions regarding therapy in concert with their healthcare providers. I would argue that even though the majority of patients with SCD may not be candidates for a stem cell transplant, it is important to inform patients and their health care providers of this potential option soon after diagnosis so that families can be educated about all potential therapeutic options.
Dr. Naynesh Kamani is of Indian descent but was born and grew up in Addis Ababa, Ethiopia, where he completed medical school. At that time, due to political upheavals, he had to leave the country by literally walking his way across the border. He eventually came to the United States where he continued his medical studies specializing in pediatric immunology and bone marrow transplantation. He worked in the stem cell transplant programs at Children’s Hospital of Philadelphia, Miami Children’s Hospital, and Santa Rosa Children’s Hospital in San Antonio. The bulk of his career has been at Children’s National Medical Center in Washington, D.C., where he directed the stem cell transplant program and was most recently the chair of their Institutional Review Board. In the summer of 2013 Dr. Kamani joined AABB as the Director of the Center for Cellular Therapies. Dr. Kamani feels strongly about the importance of expanding global access to quality medical care: “In third world countries children die of very common diseases that are easily treated in the developed countries. I saw a lot of kids that should not have died, die because of their inability to access good health skills.”
Cord Blood Transplants for Thalassaemia in India
Cord Blood transplants have come of age. Nearly 26 years after the first cord blood transplant in Oct. 1988, over 650,000 umbilical cord blood units have been stored in public banks for transplants worldwide, and over 3 million cord blood units are stored in family cord blood banks all over the world (Reference: Parent’s Guide to Cord Blood Foundation). Over 30,000 cord blood transplants have been performed globally.
Current estimates suggest that 10,000 children are born each year in India with thalassaemia. Transplantation of blood-forming (haematopoietic) stem cells offers the only hope of cure for a number of diseases of childhood, both malignant and non-malignant, including thalassaemia. The preferred donor is a matching sibling, but with a growing number of one child families and only a one in four chance of a sibling being a match, there is an increasing need for matched unrelated donors.
LifeCell International, India’s first and most accredited private cord blood bank, has over a hundred collection centers in India and abroad and stores over 95,000 cord blood units. LifeCell has released 30 successful cord blood transplants till date, out of which 21 were for thalassaemia. The majority of the cord blood transplants were carried out by Dr. Revathi Raj, Consultant in Haematology, Apollo Hospital Chennai.
The detailed patient outcomes were as follows: The youngest patient was 2 years and the oldest 9 years in age. There were 9 males and 12 females. A standard chemotherapy conditioning regimen was used in all the patients to prepare them for the cord blood transplant. One patient had bleeding in the intestines and ran a fever before immune system recovery (febrile neutropenia). Mildly elevated blood pressure was seen in 5 patients and 1 patient had low blood pressure. However 1 patient had hypertensive encephalopathy with convulsions from a toxic reaction to the DMSO preservative in which the cord blood was stored. Otherwise the transplant patients had a smooth recovery. On follow up, 95% of the patients had disease-free survival.
Ideally the HLA type of the transplanted cord blood unit should be 6 out of 6 match to the patient, but 5 or 4 out of 6 were also accepted. To increase the stem cell dose, some patients received both cord blood and bone marrow from the same sibling donor.
In India, the cost of a stem cell transplant with your own cells (autologous) is USD 10,000 to USD 12,000 while the cost of a transplant with donor cells (allogeneic) is USD 18,000 to USD 20,000.
In India there is no national bone marrow donor registry and hence patients in India who do not have a matching sibling face a problem in finding a donor. Approximately 100 to 125 umbilical cord blood transplants are carried out in the country annually. The major transplant centres in India are CMC Vellore, Tata Memorial Hospital Mumbai, Army Hospital Delhi Cantt, Tata Medical Centre Kolkata, AIIMS New Delhi and Apollo Hospitals.
It is our hope at LifeCell, that by providing families in India with a means to store their children’s sibling cord blood, more children will receive cord blood transplants to cure thalassaemia and other inherited blood disorders.