Haploidentical Bone Marrow Transplantation (BMT) is a procedure in which, instead of fully HLA matched family donor, a half HLA matched parent or sibling is the donor for bone marrow or blood stem cells.
What is the scientific basis for Haploidentical Family Donor BMT? Is BMT possible from a half matched unrelated Donor?
The saying that ‘nature is the mother of all inventions’ is not without reason. HLA antigens are inherited as a set from each of the parents. A mother nurtures a baby in her womb for 9 months without rejecting it even though the paternal HLA antigens inherited by the baby should cause a rejection. This is nature’s example of development of tolerance and thus, a child and the mother are natural donors for each other in most cases even though they are only half matched in their HLA antigens.
Based on the pioneering work by doctors from Italy, BMT from a half matched (Haploidentical) donor from the family was developed.
DUE TO THE ABSENCE OF THIS ‘NATURAL LAW OF TOLERANCE’, BMT FROM A HALF MATCHED UNRELATED DONOR IS NOT POSSIBLE.
Donor Selection for Haploidentical BMT
It is easy to find donors for haploidentical transplantation. These donors can be our parents, children and 90% siblings. The success of Haploidentical BMT lies in the proper selection of Haploidentical Family donor amongst all of the family members. For this, our doctors have carried out extensive research and shortlisted the following factors:-
Patient Related Factors
1. General condition of the patients
2. Nature of the disease
3. Presence / absence of certain cell types and receptors
Donor Related Factors
1. Presence / absence of certain cell types and receptors
2. Presence / absence of anti-cancer cells
UNLIKE UNRELATED DONOR BMT, IN HAPLOIDENTICAL FAMILY DONOR TRANSPLANTATION THE EXTENT OF MISMATCH DOES NOT MATTER IN OUR HANDS.
Haploidentical or half matched donor BMT is the only treatment option available for patients of blood disorders, who have been advised BMT, but do not have a fully HLA matched family donor or a matched unrelated donor. Before starting the success story of Haploidentical Transplantation, we must understand certain basic facts about the following:-
1. What is Haploidentical Transplantation?
2. Why is Haploidentical Transplantation required?
3. What is a graft and what is graft versus Host Disease or rejection of graft?
4. Why did it take Bone Marrow Transplant Physicians more than two decades to make Haploidentical transplantation a success story?
5. How can one prevent Graft Versus Host Disease (GVHD) and increase success rates of Haploidentical Transplantation?
There are six private and two state-owned BMT centres in Delhi and NCR and one might query intuitively as to ‘why another one?’ To answer this we need to look at the Indian scenario in the field of BMT. It is estimated that over 30,000 patients per year in our country need a BMT to save their lives and the statistics from Indian Stem Cell Transplant Registry reveals that with over 40 centres across the country, only about 1000 transplants are performed annually. So is our venture just to add a few numbers to the mammoth need of our population? If all the centres performed 4 transplants per month which we are sure they are capable of, the need would be largely met. Then why is that not happening? The answer lies in the fact that BMT is dependent on availability of HLA matched donors from the family. However, this is available to only 20% of the patients by simple law of inheritance. Yet, Europe, USA and Japan meet their needs largely through Volunteer Unrelated Donor Registries which currently boast of 20 million donors. In India, such registries are in their infancy and the chance of finding a match from the foreign registries is less than 10%. More importantly the cost of procuring the blood or marrow products from Europe or USA ranges from 10,000-30,000 USD. Similar transplants can be performed from unrelated cord blood units at a similar cost, but the procedure is more challenging.
Everyone has a donor and we are showing the way! In a country where alternate donor BMT is rarely available for patients lacking a matched family donor, Haploidentical BMT seems to be a logical option. However, the lack of expertise and infrastructure halted its development. Dr. Suparno Chakrabarti pioneered the first Haploidentical BMT program in India and Dr. Sarita Jaiswal joined the program after a year. The program was supported by Prof Paul O’Donnell from Fred Hutchinson Cancer Research Centre, Seattle and Prof Franco Aversa, University of Perugia and Parma in Italy. Their work and research was widely presented and published in the last three years. Having performed over 20 such transplants, they wanted to develop this procedure further and moved to Dharamshila Narayana Superspeciality Hospital, where they gave shape to the decade-long aspiration of Dr Suversha Khanna to develop a state-of-the art BMT Centre.
Dr. Sarita Jaiswal trained under Prof. Franco Aversa from Italy, who is the pioneer of Haploidentical BMT. Prof Aversa and others have developed a completely new approach to Haploidentical BMT using Clinimacs based manipulation of graft, which has drastically reduced the rate of complications and mortality experienced earlier. This is a labour intensive technology and carrying out such transplants without the right expertise or infrastructure can be disastrous. Dr Sarita also had the privilege of training in BMT at the largest BMT centre of the world ie Fred Hutchinson Cancer Research Centre, Seattle. The experience at University of Parma under Prof Aversa and at Seattle inspired Dr Sarita to develop the Haploidentical BMT program in India to make the procedure affordable and available to all.
The team at Dharamshila Narayana Superspeciality Hospital led by Dr Sarita Jaiswal and Dr Suparno Chakrabarti performs Haploidentical BMT on a regular basis for all malignant and non-malignant diseases where BMT is indicated. They have transplanted over 85 patients from Haploidentical family donors since 2010 and notably, 54 of those took place in the last 36 months. The success rate has now touched 80% for all diseases.
As recognition of their research, the study was selected for an oral presentation at the Annual BMT meeting of American Society of Blood and Marrow Transplantation (ASBMT) and Centre for International Bone Marrow Transplant Registry (CIBMTR) in February 2015 at San Diego, USA. Dr Sarita Jaiswal presented their study of Haploidentical BMT on 41 patients demonstrating improving outcome in both leukemia and aplastic anemia over the last 4 years (https://bmt.confex.com/tandem/2015/webprogram/Paper5949.html). The innovations in the field emanating from India were an eye-opener for all present in the meeting. Dr Jaiswal presented the data on how they have selected anticancer cells from the donors and given them to the patients after Haploidentical transplantation. It was indeed heartening to see that we are not blindly importing technology, but creating our own to meet our own needs. Dr Sarita Jaiswal now leads the Haploidentical BMT program at Dharamshila Narayana Superspeciality Hospital, New Delhi, which is equipped with the best clinical and laboratory infrastructure to carry out such transplants.