TITLE:CORD BLOOD TRANSPLANTS FOR THALASSAEMIA IN INDIA
INTRODUCTION:Cord blood transplants have come of age. The use of umbilical cord blood stem cells as a potential source of haematopoietic stem cells was first demonstrated in 1982 by Hal Broxmeyer. The fundamentals of collection, processing, cryopreservation and thawing cord blood stem cells on a large scale was laid down by Dr Pablo Rubinstein in 1992. Nearly 26 years after the first cord blood transplant in October, 1988 , by Dr Eliane Gluckman in Paris . Together, they have pioneered the use of cord blood stem cells to help achieve miracle cures for many patients with no other hope alongwith Dr John Wagner in Minnesota and Dr Joanne Kurtzberg in Duke’s university. In India the first Public Cord Blood Bank was set up by Brigadier Paramjit Dhot, in 2000, at Armed Forces Medical College , Pune. Over 7000,000 umblical cord blood units have been stored in public cord blood banks for transplant worldwide, and over 3 million cord blood units are stored infamily cord blood banks all over the world. An estimated 40,000 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 (haematopoetic) stem cells offer the only hope of cure for a number of diseases of childhood both malignant and non-malignant including thalassemia. The preferred donor is the matching sibling , but with the growing number of one child families and only a one in four chance of a sibling being a match, there is increasing need for matched unrelated donors. Life Cell International, India’s first and most accredited private cord blood bank, has over a 100 collection centres in India and abroad and stores over 1,30,000 cord blood units. Life Cell has released 34 cord blood transplants till date, out of which 24 were for thalassaemia. Majority of transplants were carried out by Revathi Raj, Consultant in Haematology, Apollo Hospital Chennai.
MATERIAL AND METHODS: Cord blood units were retrieved from Lifecell International Cord Blood Bank following all precautions as per the SOP. Prophylactic antibiotics included daily acyclovir and mycafungin intravenously and one dose of cefaperazone sulbactum were given just before infusion of cord unit. This was based on the initial experience of gram negative bacteraemia following infusion of the cord unit and also on the prevalence of azole resistant candida in our unit. Conditioning varied from total body radiotherapy for the children with leukaemia to fludarabine and treosulphan based protocols for the benign conditions. This period was generally well tolerated and there was no mortality during this period. Infants needed a dose reduction in treosulphan to 36 gm/m2 from 42 gm/m2 and were more prone to treosulphan rash in the perianal region. A peculiar conjunctivitis with red eye was also noticed with treosulphan in infants.
RESULTS: The detailed patient outcomes were as follows: The youngest patient was 2 years and the oldest 9 years in age. There were 11 males and 13 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 a low blood pressure.
However, 1 patient had hypertensive encephalopathy with convulsions with a toxic relation to DMSO preservatives in which cord blood was stored. Otherwise the transplant patients had a smooth recovery. On follow up, 95% of patients had disease free survival.
DISCUSSION: 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, only 100,000 donor base is available in the bone marrow 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. There are a total of 43 Stem Cell Transplant Centres in India .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.
CONCLUSION: In India, Family Cord blood banking was started by Lifecell International in 2004. In the future, it is expected that Cord blood transplantation will be the mainstay in the therapy for malignant and nonmalignant disorders. Stem cell science represents to those afflicted with chronic disease a vehicle for disease free survival. Moreover regenerative medicine, cellular therapy and tissue engineering will offer a panacea for the needy patients. 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