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EBMT 2021 | Novel scoring system defines allo-HSCT patients at high risk for CMV

Ibrahim Yakoub-Agha, MD, PhD, University of Lille, Lille, France, discusses the development of a scoring system to define patients who are at a high-risk of cytomegalovirus (CMV) infection following allogeneic hematopoietic stem cell transplantation (allo-HSCT). Treatment of CMV infection can have severe side effects such as cytopenia and renal impairment. A prognostic scoring system could help to assess the value of anti-CMV prophylaxis for individuals based on their risk of CMV infection. Prof. Yakoub-Agha describes how a retrospective analysis of 3690 patients was used to develop a prognostic scoring system using CMV-seropositive donor, unrelated donor (HLA matched 10/10 or HLA mismatched 9/10), antithymocyte globulin, myeloablative conditioning, total body irradiation, and mycophenolate mofetil as risk assessment factors. Four risk groups were defined. This interview took place during the 47th Annual Meeting of the European Group for Blood and Marrow Transplantation (EBMT) 2021.

Transcript (edited for clarity)

CMV infection is a big challenge after allogeneic hematopoietic cell transplantation. Actually, we know that developing a CMV infection can, I would day, compromise the outcome of the patients. It can be responsible for higher risk of morbidity and mortality. The treatment or pre-emptive treatment, or even treatment for patients developing CMV infection, we have two categories of treatment. Actually, those two drugs are, I would say, toxic for patient...

CMV infection is a big challenge after allogeneic hematopoietic cell transplantation. Actually, we know that developing a CMV infection can, I would day, compromise the outcome of the patients. It can be responsible for higher risk of morbidity and mortality. The treatment or pre-emptive treatment, or even treatment for patients developing CMV infection, we have two categories of treatment. Actually, those two drugs are, I would say, toxic for patient. The first one can trigger cytopenias, profound cytopenias, after allogeneic transplantation. And the other one, can be responsible for a renal impairment, etc. That’s why a lot of research, have been done to find how to prevent patient to develop a CMV infection.

Now we have at least one molecule and at least one drug or tool to prevent CMV infection. Actually, the question is, do we need to give these drugs to all, I would say, transplanted patients or just to those who are at risk?

First of all, we can say, yes. We need just to deliver or to give it this treatment to patient at risk. For instance, patients with a CMV positive serostatus at transplantation, but that’s to say, it’s giving this treatment to 50% of our patients. So, the idea was to investigate a more sophisticated risk factors of developing a CMV infection after allogeneic transplantations. And we conducted this retrospective study on more than 3000 patient who underwent allogeneic hematopoietic stem transplantation in centers belonging to the French Society of Bone Marrow Transplantation and Cellular Therapy, SFGM-TC. And all those patients were positive for CMV, or they have a positive serostatus at transplantation.

So, we tried to look at another risk factor, in this particular population, which is 50% of transplanted patients. So, I notify the some other factors, such as unrelated donor, the use of ATG within the conditioning and the use of MMF, transplantation from CMV negative donor, for instance. And we built up a scoring system and we could broke down the old cohort, within four categories for CMV infection risk. So, we had this low-risk CMV infection, intermediate 1, intermediate 2, and high-risk.

According to this new scoring, so we may, first of all, decide if we give prophylaxis treatment to the patient or not. It’s difficult to you know, to give you a firm conclusion on this. But if you are asking if you can add a new treatment to drug for your patients, because they are receiving a lot of other drugs and you are worried about drug interaction, etc. So, you can use this scoring system to decide if my patient is at lower risk of CMV infection, maybe I don’t need to give right away prophylaxis, and then we can wait and see. In this case, for instance. And this scoring system can be really helpful for prospective studies so that we can identify the patient prospectively who are at risk of developing CMV, according to the prophylactic treatment they are receiving etc. So, for us, it was the first study, you know, trying to go in depth with this scoring system.

Of course, this is a retrospective study and we have the limitations of all retrospective studies. Also, the results seem to be really reliable, you know, but we need to confirm this in prospective, I would say, investigation. And another example, I can tell you, for instance, when you start your transplantation, so your patient, is at low risk of developing CMV, so, maybe you decide not to give them the CMV prophylactic. And then I would see a three, four months later, the patient develops acute GvHD and you need to give them corticosteroids and add another immunosuppressive treatment. And this case, your patient who were at lower risk at the beginning becomes a patient with high-risk because we know that the risk of developing CMV, it’s a risk that depends on many other factors, such as the advent of acute GvHD requiring corticosteroids.

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Disclosures

Prof. Ibrahim Yakoub-Agha, MD, PhD, has received honorarium from MSD and Biotest.

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