STATUS OF BONE MARROW TRANPLANT IN INDIA

What ails Bone Marrow Transplant in India

Bone Marrow Transplant programme, started way back in 70s, is crippled by expensive treatment, lack of specialists and shortage of transplant centres, finds out Shardul Nautiyal

Even as around 1000 patients require bone marrow transplants (BMT) every year and ideally 50 BMT centres should be offering the treatment, only around 200 patients are receiving the treatment annually from 15 BMT centres across the country. Of 15 BMT centers across the country performing both autologous and allogeneic transplants, 12 centres are performing BMTs regularly, inform experts. (See box for centres performing BMT).
BMT involves taking out stem cells from BM (cells present in the bone marrow). These are also present in blood (peripheral blood) in very small amount, in this case of a donor (sibling or unrelated) to be given to the patient/recipient (called as allogeneic BMT).

Why we require more BMT centres?

More BMT centres are required because the need for BMT is alarmingly high in malignant and non-malignant diseases all over India. Hospitals, having BMT facility, complain of overload of patients. For instance, CMC, Vellore has a waiting list of Indian patients for elective BM transplants till the June of next year. Besides this, BMT centres in India are attracting patients from countries like Pakistan, Maldives, Muscat, Oman, Dubai, Nepal and Mauritius.
According to Dr P M Shah, director, Gujarat Cancer Research Institute (GCRI), Ahmedabad, “The lack of centres is due to limited facilities in hospitals, high cost of treatment and less number of trained oncologists or BMT specialists in this field.”
Successful running of the BMT centre is possible only if we have dedicated oncologists. Says Dr P S R K Sastry, consultant medical oncologist, Tata Memorial Hospital, Mumbai, “After chemotherapy, there are complications like neutropenia, oncologists therefore play the role of a specialist and require a great deal of expertise.”
According to Dr Mammen Chandy, head, BMT Centre, Christian Medical College (CMC), Vellore, “Most doctors after doing D M (oncology) do not take much interest in this speciality as BMT is very difficult to perform.”
Orchestrating extensive support system is another arduous task. The support system requires trained oncologists, nursing staff, blood bank officers, radiation therapist, pathologist, microbiologist, biochemist and radiologist.

Status of BMT

Though the past decade has seen a dramatic and dynamic expansion in the clinical discipline of bone marrow and peripheral blood stem cell transplantation, BMT is still in infancy in India, feel experts. BMT programme in India is still not developed to tackle the patient overload in the country and from overseas.
According to Dr Lalit Kumar, medical oncologist, All India Institute of Medical Sciences (AIIMS), lack of awareness among the general or referring physicians, who refer the patients late, lack of co-ordination among the various departments in hospitals, where this facility is available and the cost involved contribute to its slow growth. “Increase in efficacy and safety of this mode of therapy is mainly due to refinements in technologies, supportive care and due to expansion of scientific knowledge of hematopoiesis and immunology, “ adds Dr Shah.
Success and advancement of BMT
Says Dr Maheboob Basade, medical oncologist, Jaslok Hospital, “Success rate is variable for BMTs in India. Overall mortality is less than five per cent for all kinds of BMT performed. It is less than one per cent for autologous BMT and less than 10 per cent for allogeneic BM transplants.”
It has been observed that the risk to the life due to Graft versus Host Disease (GVHD) occurs mostly in cases of allogeneic BM transplants. Experts pinpoint that mortality is more in matched unrelated transplants in comparison to matched related BM transplants. “Results in controlling GVHD has improved with the advent of newer drugs, effective in better immuno-suppression. The drugs are effective in selectively discarding T-cells or T-lymphocytes, which causes GVHD,” opines Dr Basade.
When BM transplantation was initiated for the first time in 1970, BM was used as a source of stem cells. But now almost 60 per cent of allogeneic transplants and almost 99 per cent of autologous transplants are being done using peripheral blood stem cells. “More than 6000 children and young adults also underwent transplantation using umbilical cord stem cells with equally good results,” says Dr Kumar.
Advancement in BMT are cord blood transplant, mini transplants and unrelated registry transplants. Other new developments are use of stem cells in the treatment of non-malignant diseases such as repair of myocardium and neurological disorders.
Other major advances in the field of hematopoietic stem cell transplantation are collection and purification of stem cells so that haplo-identical (half matched) transplants can be performed. “This implies that every patient can have a donor, as in this case, a parent will be half matched with the child. Another upcoming area is the use of stem cells for the purpose of gene therapy,” informs Dr Chandy.

The cost

Most hospitals are discouraged to have a BMT unit as the cost of setting it is very capital intensive and costs around Rs one crore.
The basic requirement to set up a transplant unit is hepa-filtered positive pressure rooms, facilities for collection, processing and cryo-preserving stem cells, with a support system in place like HLA lab for tissue matching through serology or preferably molecular based HLA typing. HLA typing generally costs Rs 3,000 to Rs 6, 000 per patient. The support system should also comprise of a bio-chemistry, microbiology and a blood component program.
The HLA typing lab is a capital intensive set up comprising a thermal cycler costing around Rs four lakh, Gel Documentation System costing around Rs four Lakh and the cost of the consumables like HLA trays costing around Rs 5,000 per tray. An electrophoresis instrument costing around Rs 1, 000 is also required.
The cost of BMT is generally around Rs 6-8 lakh for autologous and 10-12 lakh for allogeneic transplant. While the expense incurred on the BMT is estimated in actuals in a centre like TMH, centres like Jaslok Hospital offer a packaged deal.
The cost of BMT is expensive because of the cost incurred on the growth factors, for which one requires a cell separator and consumables. A cell separator, costs around 20 lakh and consumables costs Rs 100 USD per sitting on an average, depending on the patient, which is the recurrent cost.
Says Dr Harish Ahuja, senior pathologist and blood bank officer, Jaslok Hospital, “Stem cell harvesting contributes around 15 per cent of the cost for BMT, which also includes the cost of the disposables and consumables costing around one to Rs 1.5 lakh.” A BMT centre can ideally perform 15 to 18 cases a year, if the transplants performed are on a no-profit, no-loss basis.
One factor impacting the cost is that BMT is not covered under health insurance. “Only a small fraction of BMT cost can be reimbursed through insurance,” says Dr Sastry.

Lack of donors

BMT is also plagued by lack of donors. The chance of finding a matched related donor in a family is 25 per cent and one in a million for a matched unrelated donor. The situation becomes grave because of the lack of a wider donor pool for Indian patients requiring a matched bone marrow not only in the country but also globally. “It is difficult to find a match for Asians in registries from North America, Europe or Canada because Caucasians and Asians have a different set of genes,” says Dr Kumar.
Some of the major centres performing BMTs

Tata Memorial Hospital, Mumbai has performed over 250 BMTs till date with around 40 BMTs per year. TMH performed the first allogeneic bone marrow transplant in 1983. TMH performs BMTs for chronic myeloid leukaemia (CML), hodgkins disease, leukaemia, most acute leukaemias and certain lymphomas. TMH has performed 37 cases of Myeloma, 12 cases of thalassaemia major and 90 cases of CML till date.
Jaslok Hospital, Mumbai has performed around 70 transplants mostly in leukemia, myeloma, lymphomas and aplastic anemia. Country’s first and successful transplant for sickle cell disease was performed at Jaslok Hospital on a young Omani boy three years back.

Christian Medical College, Vellore has performed 506 allogeneic bone marrow/stem cell transplants and 109 autologous stem cell transplants since1986 and currently six allogeneic and three autologous stem cell transplant are performed every month. Allogeneic transplants have been done for thalassemia (160), Chronic myeloid leukemia (60), acute leukemia (60) , aplastic anaemia or a bone marrow failure (54) and many other conditions including rare genetic immuno-deficiency states. Autologous transplants are done mainly for acute leukemia, myeloma and lymphoma.The private mission hospital houses a three-bed stem cell translant unit, which will be upgraded to a ten-bed transplant unit very soon.

Apollo Hospitals, Chennai has has done 159 transplants till date including allogenic, autologous, cord blood and mini transplants. The commonest transplants were for multiple myeloma, acute myeloid leukemia and acute lymphoblastic leukemia. Transplants have also been done for thalassemia, aplastic anemia, and solid tumours. Nearly 75 per cent patients got discharged well after the transplants and more than 60 per cent are long term survivors.

ALL INDIA INSTITUTE OF MEDICAL SCIENCES, New Delhi is doing almost 30 transplants annually. The centre completed 216 transplants till June 2005 and has the largest series on myeloma and has completed 79 transplants. The centre is currently using BM stem cells for the repair of myocardium and certain neurological disorders. AIIMS is trying to evaluate the role of stem cells in the treatment of certain eye diseases.

Kidwai Memorial Institute of Oncology, Bangalore started the transplant unit six months back and has performed three cases of myeloma.
Gujarat Cancer Research Institute, Ahmedabad performs one to two transplants in a month. The unit was started one year four months back and 32 patients have undergone BMT/PBSCT. The centre mainly focuses on conventional fully HLA matched sibling BM transplantation and autologous BM transplantation mainly in patients with malignancies.

Why we require bone marrow registry

To address the problem of lack of donors, the formation of a bone marrow registry is necessary. Having a good HLA typing facility is required to kick-start a bone marrow registry. Such registries are well developed in the west, but yet to make a beginning in India. In the absence of an operational bone marrow registry, TMH is in the preliminary stages of performing haploidentical HLA typed BM transplant cases.

Suggestions for improvement

A step by step approach is required to set up a BMT centre. “The BMT centre should perform autologous transplants first and then gradually switch over to allogeneic transplants. Performing autologous transplants first ensures that the BMT centre grows logistically,” opines Dr Sastry.
Experts say that autologous BMT is ideal as comparable to allogeneic BMT because there are less chances of infections in autologous transplants and therefore no risk of having GVHD.

According to Dr T Raja, senior consultant medical oncologist and senior consultant, BMT, Apollo Hospitals, Chennai, “In order to give a boost to allogeneic BMTs, the government needs to urgently set up good centralised HLA lab for all the hospitals across the country on payment basis. This will increase the chances of finding suitable donors within the country for many needy patients.” Patients undergoing BMT are also reported to have developed infections. Says Dr Vinod Raina, professor, medical oncology, AIIMS, “We are losing 10-30 per cent of transplant patients (depending on the type of transplants performed) and due to infections, many of which are fungal infections. This mortality due to infections can come down if facilites are improved and hospitals are made cleaner.”

The good news is that supportive care for infections and management of some of the complications has improved, reducing the risk of mortality to almost less than two per cent for autologous and less than 10 per cent for allogeneic transplant, say experts.
Experts suggest more involvement from the government, as the government has not been of much help in giving this specialty a boost. “Most of the pioneering work is done by the individual institutions in the various parts of the country,” says Dr Raja.

shardulnautiyal@rediffmail.com