The Aplastic Anaemia Trust turns 40 this year, and we have made a special treat for you to celebrate. We invited Professor Ted Gordon Smith to Kings Hospital to meet with Dr Austin Kulasekararaj and discuss treatment for aplastic anaemia and how it has improved.

This is the final video in our little series - we hope you have enjoyed watching them! Given all the improvements over the past 40 years - what should we be looking forward to in the next 40? Professor Gordon Smith and Dr Austin share what they're most excited about:

Video transcript

Dr Austin: What do you see as a blue sky thing - what do you think will change in the next 20, 30, 40 years?

Prof Ted: Gosh, um. I think you have actually indicated it in what you’ve said already: the problems we faced 40 years ago, 30 years ago are still here. They’re modified, and much better and the results are considerably improved but they’re still the same challenges. 

What is the cause of aplastic anaemia? What is the target? If there is indeed an auto-immune function? I’m particularly interested in the micro-environment in the bone marrow,  the niche. I know my dear colleague Professor Marsh, when she was at Manchester, showed in some experiments that it’s probably the stem cell that’s the target but I’m not totally convinced - I think the target might be in the niche. 

And the other thing that really fascinated me - well one of many that fascinated me about aplastic anaemia - is: some people get better. And also after bone marrow transplantation the marrow regenerates and, in some cases, it’s the patient’s own marrow. 

But I want to hear about your stuff because it’s a long time since I practiced and things have improved a great deal. You could tell us about eltrombopag for example, you’ve touched on the wonderful work with haploidentical transplants, and now you’re into identifying a target for autoimmune things - your latest trial?

Dr Austin: Yeah we are trying! So I think a couple of things, historically you touched on how transplant evolved or started in aplastic anaemia in the 70s and as you very much said, there has been trials of doing half-matched haploidentical transplant, even in the 80s or 90s, but it unfortunately had significant complications. But I think in the last 10, 12 years through the Johns Hopkins Baltimore approach of using post-transplant cyclophosphamide on Day 3 and Day 4, being able to overcome that barrier of half-matched transplant so people without any identical sibling donors or unrelated donors - we’ve been able to offer haploidentical transplant. And it’s quite critically important for ethnic minorities, non-caucasians who do not have matched donors in the registry, and with ever shrinking family sizes as well. So that is now being taken as very much a standard of care, that we can offer transplant. So at least if someone is generally fit without significant medical problems, transplantation should be always thought about in anyone who walks in with aplastic anaemia, either as a second line or a third line in the context of haploidentical transplant - so that has definitely changed our spectrum of thinking on the treatment management. 

The second thing you talked about is: we’ve always been stuck with a  60-70% response rate with horse ATG with ciclosporin and steroids (mainly for serum sickness prevention). So eltrombopag - again I always like this context of serendipity in medicine, because I know you’ve done studies looking at TPO levels in aplastic anaemia, it’s extremely high. Thrombopoietin (TPO) is a hormone which stimulates the production of platelets and nobody felt that eltrombopag would have an effect. So they did, NIH did, an extremely small study of using eltrombopag for patients who had refractory relapsed and had extremely high levels of this hormone - but they found surprisingly that 40% of patients had a response. So what we have done is, similar to the context of using [eltrombopag] - do we need to use some similar drugs to stimulate the bone marrow as well? - As well as suppressing the immune system? We’ve added in ATG, ciclosporin, with eltrombopag and nearly 80-90% of patients have a response. And also they get a rapid response - ie they get a response within three months. And the proportion of patients who get a complete response has also gone up from 10% to 30-40% as well. 

Prof Ted: Brilliant. 

Dr Austin: And they are able to come off the eltrombopag. So that’s one! And as you know we are trying to do more trials, through The AAT and other funders, using autologous T regulatory cells, expanded autologous T regulatory cells from patients, expanding them outside and then re-infusing them back to patients. This is a very early phase trial but it is fascinating and you know we are very much interested in studying the clonality, ie the mutations in patients with aplastic anaemia. Why would a disease that is purely an auto-immune disease have genetic defects in the bone marrow stem cells? And that is quite fascinating as well and we are trying to see whether we can look at it to see whether we will be able to identify patients who potentially can go on to develop acute myeloid leukaemia and MDS which, as you said - we don’t want them to get. It’s less than 10-15% but we don’t want patients to go on to develop leukaemias and myelodysplastic syndrome.