AML: New Strategies For Preventing Graft vs Host Disease | Giorgia Battipaglia, MD | #ASH24

Good morning everybody. My name is Dr. Giorgia Battipaglia and I work as an hematologist in Naples, Italy, and I'm an expert in transplantation, especially allogeneic hematopoietic stem cell transplantation. And, tomorrow, I'm going to present data from the European Bone Marrow Transplantation Society about different prophylaxis for an important complication of allogeneic stem cell transplantation, namely graft versus host disease, particularly in patients undergoing allogeneic transplantation from donor- different from a related donor from donor registries.

And, our study focused on the use of two different GvHD prophylaxis strategies, namely anti-tumor globulin and post-transplant cyclophosphamide. And we focused on the use of antithymocyte globulin ATG in the matched the unrelated donor setting. That's 100% compatible donor non familial donors receiving ATG, as GvHD prophylaxis strategies compared to patients undergoing transplantation with a one antigen mismatched, unrelated donor with the use of post-transplant cyclophosphamide as GvHD prophylaxis.

And what we observed is that despite the presence of mismatches in the HLA system, that is one of the major driver in the complications of transplantation, including GvHD, the use of post-transplant cyclophosphamide in mismatched non-related donor setting allowed similar transplant outcomes compared to ATG in the 100% compatible unrelated donor, so they matched non-related donors and so this allows to overcome the HLA barriers and reduce the major complications of allogeneic stem cell transplantation.

As people probably know, among donor registers, we may identified in nearly 76% of patients a match non-related donor. That is the best donor we may identify in a donor registry. But for patients that do not, find an available match, non-related donor potential options are either a haploidentical donor that's familial donor, we can say 50% compatible, and also mismatched, not related donors.

So the possibility to improve, transplant outcomes with the with the use of new GvHD prophylaxis strategies also allowed to, have similar outcomes in when using donors with more HLA mismatches, does, opening the possibility in patients that do not have a matched non-related donor to undergo transplantation with similar outcomes to those that are completely compatible?

Okay, so, cyclophosphamide is a drug that, has an history. I mean, it has been initially used immunosuppressive, but also chemotherapy. And, the first publication about its use in the haploidentical setting belongs to, the group of Leo Luznik in 2008 and showed in the haploidentical setting. So it is setting where HLA mismatches are their maximum expression, so that the addition of post-transplant cyclophosphamide, the allowed significant reduction in GvHD incidence.

And so the use of post-transplant cyclophosphamide has been subsequently extended to other donor setting, including, of course, unrelated donors, showing that the these strategies allow to significantly reduce GvHD and also as in our study either allows similar outcomes as in other better HLA matched donors or even better outcomes, compared to other GvHD prophylaxis strategies with the same HLA compatibility.

For example, in the mismatched, not related donor setting, we compared the same. We compare post-transplant cyclophosphamide to antithymocyte globulin and observed that post-transplant cyclophosphamide is superior strategy. So these strategies really represented the major revolution in the GvHD prophylaxis of this patients is a cheap drug. It's easy to manage. And it being and historic drug people really easily know how to manage this drug.

So GvHD is the acronym for graft versus host disease and represents the conflict we observed between donor T lymphocytes that do not recognize the organs of the patient. So the organs that represent the non-self part. And so the donor T lymphocytes aggress the organs of the patient. And we can distinguish two forms of graft versus host disease occuring after allogeneic stem cell transplantation acute graft versus host disease.

That is the early graft versus host disease. And that has its major targets in the skin, gut and liver. And we can also observe chronic GvHD that may ideally interest every organ. And it's the less common complication we may say, but it's also a major cause of morbidity and mortality after transplantation, especially when it's in an extensive form.

When people experience acute GvHD, they either have erythema of the skin, that's to say that the skin becomes red, and sometimes with itchy symptoms, and while for gut GvHD, the major symptom is diarrhea that may become really, really important. So of course, patients experiencing this complication, even if they were discharged after transplantation, they may need when diarrhea is important to be hospitalized again and liver complications, liver GvHD, more often expresses without major clinical symptoms.

So it's the biochemistry exam that allows the identification of this complication. On the other hand, for chronic GvHD, symptoms may be subtle, especially in the limited form. And so it's really important for continuous follow up over the years in these patients because limited form are easily manageable. But as I previously said, sometimes this complication may develop in a more extensive form when important complication and major constant problems for patients, survival.

I hope that, our research will open, new strategies for GvHD prophylaxis, improving the existing strategies. Of course, we have observed major, progresses in the transplantation fields all over the years that have allowed to significantly reduce the incidence of GvHD. And so the but the problem of GvHD remains actual. So really looking for GvHD prophylaxis strategies that are not toxic and that reduce significantly the incidence of this important complication are warranted.

And so I hope that our, research activity with the post-transplant cyclophosphamide compared to, ATG strategies will really make it more understandable, what is the best strategy for GvHD prophylaxis to use.