An analysis of the worldwide utilisation of haematopoietic stem cell transplantation for acute myeloid leukaemia

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Published: 14 Dec 2022
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Dr Molly Tokaz - Fred Hutchinson Cancer Center, Seattle, USA

Dr Molly Tokaz speaks to ecancer as part of ASH 2022 about her study 'An analysis of the worldwide utilisation of haematopoietic stem cell transplantation for acute myeloid leukaemia'.

She explains that estimates of AML incident cases in 2016 were obtained from the Global Burden of Disease (GBD) 2019 study and HSCT activities were collected from 2009-2016 by the Worldwide Network for Blood and Marrow Transplantation (WBMT).

Dr Tokaz reports that from 2009 - 2016 incidence of AML globally increased by 16.2% and during this time the use of stem cell transplant increased by 54.9%.

She concludes by stating that she was surprised by the altogether low utilisation rate of stem cell transplant for AML globally.

The reason we chose to do this study is that there is a mounting global cancer crisis, and by 2040 we’re expecting cancer cases to double in low income countries, which are the regions that are least equipped to deal with this pending cancer epidemic. Among hematologic malignancies, AML remains the deadliest disease with a five year overall survival of less than 30%, and for these patients with high-risk disease stem cell transplant really remains the only curative option. Thus, how available stem cell transplant is globally affects potential patient outcomes in this deadly disease around the world. There have been no studies to date looking at the global use of stem cell transplant for AML, so our goal with this study was to really understand what the incident trends are of AML, and what the use of stem cell transplant was globally, to really understand where are the gaps in care that we might be able to focus future efforts at closing.

What was the methodology used in the study?

We had two data sources: one is from the Global Burden of Disease Project, which is out of Seattle here, that looks at incidents globally and uses the model to predict incidents in places that we don’t have raw data. We used their 2019 study to obtain information for incidents in 2016. The other data source we have is from the Worldwide Network of Blood and Marrow Transplant, which is an organisation that collates information on transplant globally from member organisations. From them, they have a standardised reporting structure, so we gathered information about our primary endpoint which was global and regional use. We also had secondary outcomes from that, including trends from 2009 to 2016, in donor type used – related versus unrelated, haploidentical – stem cell source used, so bone marrow, peripheral blood, cord, and then remission status at time of transplant – in complete remission one versus not in complete remission one. We then used the regional use data and correlated it with our incident data to come up with a calculation of utilisation of stem cell transplant.

What were the key findings?

So, one of the first key findings is just sort of a description of what’s happening with incidents of AML and the use of stem cell transplant globally. Over our time period from 2009 to 2016, incidents of AML globally increased by 16.2%, up to 118,000 in 2016. During this time the use of stem cell transplant similarly increased by 54.9%, and this reflected an increase in allogeneic stem cell transplant, increased by 64%, almost 65%, with a simultaneous reduction in the use of autologous transplant for AML, down about 35%. This decrease in autologous was seen in all regions except Southeast Asia and Western Pacific, where overall stem cell transplant and autologous stem cell transplant remained rather low but steady over this time period.

I think one of the most important or surprising findings to us was just the low utilisation rate of stem cell transplant for AML that we saw globally, given that this is a curative treatment. It was really an unfortunately low percentage across the globe. So globally, stem cell transplant was less than 20%, which leaves a lot of room for improvement in all regions of the world. In places like Europe and North America, that are our most resource abundant regions, stem cell transplant for younger patients, which is the patient population most likely to be transplanted, and we use a circuit of less than 70 years of age, stem cell transplant only reached like 40%, and 35% in Europe. These are in our resource abundant countries, really showing that we need to increase uptake, even in places where stem cell transplant is available at least geographically.

This was compared to really huge gaps we saw in utilisation in other parts of the world, and especially parts of the world dominated by low resource countries. In Africa and the eastern Mediterranean the utilisation rate was 3%, and in Latin America it was really at about 5.8% in 2016. You know, I think we were not surprised that those numbers were lower, given different healthcare structures and resources, but I think the degree in which that decrease was seen was surprising and really, really demonstrates the need for us to increase our efforts to provide stem cell transplant to patients globally, and to affect possible outcomes.

I think the other thing just to mention is those secondary outcomes, where we looked at donor source, stem cell source and timing of transplantation. Across the world, there’s a global trend towards early transplantation, in complete remission one, and there’s also a trend towards peripheral blood stem cell use. Most recently it was at almost 80% in 2016 of transplants occurring with peripheral blood stem cells. The one place that there was a little bit more geographic variation was in donor source, and overall, globally, there’s a slight trend towards related donors, but this is really distinct by region. Europe and North America still have a majority of unrelated donor sources, probably reflective of robust transplant donor sources. This is the inverse of the relationship we saw in other parts of the world, where in Africa and the Eastern Mediterranean over 95% of transplants are happening with related donors, and that’s at about 80% in South America and about 62% in Southeast Asia and Western Pacific. With these there’s also an increase in non-matched related donors, and this is important as we consider many of the factors, such as algorithms for conditioning and what that means for these different regions in a question about, what is optimised practice in different regions based on donor source, stem cell source, and timing.

What does the future look like for this study and what will be the clinical impact?

I think the future of the study really points to the importance of getting this information out there and continuing this kind of research, Our ability to implement programmes is only as good as our knowledge of what is out there and what the need is, so overall I think the goals of the future direction of our work is to continue research into the disparities in the global landscape of stem cell transplant for AML, really to hopefully provide an informational basis to affect programmatic and health systems change. I think this is going to depend on a couple of steps that are sequential. I think one is, we need to continue to bolster our ability to collect this data and really bolster our data collection infrastructure, and this needs to happen both on a local national level by strengthening population-based cancer registries in countries, in making that a priority amongst politicians and healthcare settings globally. At the same time we need tocontinue to support organisations like the WBMT, the Worldwide Network for Blood and Marrow Transplantation, which is collating this data so that not only do we have that data available, but we’re able to compare across different practice settings and really understand where those differences and gaps exist.

Then I think the second thing would be, in addition to increasing the reach of our data collection is to increase the type of data collected. I discussed what was available from the WBMT, which is an incredible organisation with a really incredible amount of data that we do not have in many other disease types, but it would be helpful to also collect information about outcomes data, financial data, age-based data, to really help provide that granularity that will be needed to help make those hard decisions about what is the right treatment in different parts of the world and what are the right models if we’re going to try to expand transplant for AML and other disease types globally in different practice settings.

I think with the ultimate goal for clinical impact, the goal would be that this really shines a light on the fact that we are really low on utilisation, far lower than hoped or expected for this disease that is very deadly and cured with transplant. So we’re really hoping that this can provide fodder for different organisations, different clinicians in different parts of the world, to really consider what these trends are and use this as a way to stimulate their own research, to be able to affect change in the places that they are practising, and for the places that are appropriate to really lobby for support for stem cell transplant. I will say the WBMT, like I’ve said, is a very impressive organisation that I’ve had the honour to work with. In addition to this data collection, which is one of their central mandates, is the programmatic and implementation side and they have successfully participated in the launching of stem cell transplant programmes in places like Paraguay, Ukraine, Lithuania, and with a pending one in Pakistan. So there is the potential for collaborations internationally to really support local clinicians or governments to start these stem cell transplant programmes for AML and other diseases where appropriate.

Is there anything else you would like to add?

I just want to really give a heartfelt thank you to everybody who collaborated with me and everyone who contributed to this project, there are many, many authors involved. So it’s a special thank you to the folks at the Global Burden of Disease Project here in Seattle who helped with the incidents data, and a special thank you to Dr Niederwieser who’s a senior author on this paper, and all the collaborators at the WBMT, both on the research side and the leadership of the WBMT, but also to all the member organisations and clinicians around the world who are taking on the onus, or taking it upon themselves, to increase this reporting and awareness.