How are the transplants becoming safer - good news for patients who seek cure from thalassemia

It has been three years since the time Sankalp started the program for thalassemia cure. We started our bone marrow transplantations for patients who had a matched related donor only. Even in this selected group of patient, recent data shows that the team has achieved 95.5% disease free survival and 98.3% overall survival last year, building upon the success of previous years. Specially in the matched sibling context, the team improved disease free survival from 89.1% across the years to 98.3% for last year alone.

One of the key reasons for steadily improving outcomes is the stringent review of the data that the organisation accumulates. For our Sankalp program for Thalassemia Cure, it is no different. Recently we reviewed our data for the transplantations again after a gap of 3 months from the last Sankalp-Cure2children network meeting. We are happy to share some of the key findings which have huge implications on enabling cure for all kids.

At the beginning of this year, Sankalp has started accepting patients who had a partial match with the parents for transplantation. These haploidentical transplantations(also referred to as haplo) are relatively new and there is very limited context appropriate published data available.

With the positive experience at South east Asia Institute of Thalassemia Jaipur and with the good outcome with the first haplo in Bangalore, we proceeded with a limited number of transplantations with partially matched parental donors. Now, when we review the outcomes we can see that in a selected group of patients the outcome of haplo is probably as good as matched sibling transplants. There are two major risk factors beside the usual risk factors associated with transplantations for thalassemia which have shown to contribute to poorer outcomes (transplant failure). The first one is the nature of mismatch. Some matches are such that there is a increased risk of the patient's cells destroying the incoming bone marrow (host vs graft reaction). The other issue that has been uncovered is the presence of donor specific antibodies in the patient prior to transplant. The patients who had neither of these issues performed extremely well. The fact that these issues have now been identified, targeted work is being undertaken to see how they can be addressed.

Nevertheless, the experience confirms that we can expand the number of children who can be offered transplants as a curative choice. Now, we will begin the process of systematically preparing more low-risk kids for routine haploidentical transplants.

It is a known fact that thalassemia transplants do not do well if the patient has severe organ damage. Enlarged liver and spleen are key risk factors. A key differentiator in our approach to transplants in the huge investment of time and effort we make together with the thalassemia families to undo the damage done by years of improper care to the extent possible. This process call downstaging is undertaken for each child and only once the medical team is confident that no further improvement can be achieved is the child taken up for transplant.

Recent review of our data shown that the intent to downstage has worked very well and an overwhelming majority of patients go into the low risk category just prior to transplant. As a consequence and also thanks to the improved protocols we have improved the outcomes significantly. With the latest protocol for all patient put together we saw an overall survival of 98% and disease free survival of 94% in our two centres.

With outcomes that set a benchmark, the next focus for fully matched related transplants is to reduce the chemotherapy to the minimum so as to spare the detrimental impact on fertility.

Both these findings give us greater confidence in our mission for a thalassemia free India. The journey of last few years have seen path breaking improvements which have made available reliable transplantation to patients with higher risks, more age and those who did not have matched related donors. While some challenges remain, the fact that they have been identified is a promise of solutions soon.

Patrika Section