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EBMT 2020 Annual Meeting - Update infectious diseases in HSCT

Pharmacist Committee

Pharmacist Day - Saturday 29 August, 16:30-17:30H, Auditorium 5

The third session in the Pharmacist’s Day programme on day one of this year’s EBMT focuses on antivirals, vaccines and antibiotics, and will be followed by a 15-minute Q & A.

In the first session, Per Ljungman (Professor Emeritus of Hematology at the Karolinska Institute and based at Karolinska University Hospital, Stockholm, Sweden) will discuss the increasing interest in antiviral drugs, but says that “there are still major gaps in the armamentarium, since there are many different viruses that can cause severe disease in stem cell transplantation (HCT) patients.”

His talk will cover the most important new addition in the field of antiviral therapy: letermovir. This new prophylactic drug against CMV significantly reduces the risk for CMV-associated complications in HCT recipients including all-cause mortality. Another CMV drug in development is maribavir, which is promising for the management of resistant/refractory infections. “However, brincidofovir - that has been available for compassionate use for adenovirus infections - is currently not available,” says Professor Ljungman. “And of course, the emergence of COVID-19 has prompted very active research to find possible antiviral drugs and remdesevir is now licensed for treatment of severe cases, although only anecdotal data is available in stem cell transplant recipients.”

In the second talk, vaccines are addressed by Dr Marjolein Hensgens of University Medical Center Utrecht, Netherlands. More specifically, she will address the current Dutch guidelines and practices. “Recent international guidelines for vaccination of patients with haematological malignancies contain clear recommendations for this population. Currently, vaccination in the Dutch population with haematological diseases is different in daily practice,” she explains.

“In this presentation I will highlight current practice in the Netherlands and summarise the recommendations of the Dutch guidelines on vaccination in patients with haematological malignancies that will be published next year. Extra attention will be given to pneumococcal vaccination in patients with chronic haematological malignancies such as multiple myeloma and CLL. Furthermore, I will address the varicella zoster subunit vaccine that became recently available in Europe.”

In the last part of this session, Associate Professor Florent Mallard, based at the Haematology and Cell Therapy Department at Saint Antoine Hospital, Sorbonne University, Paris, France, will question the importance of the effect of antibiotics on the microbiome in HSCT patients.

In recent years, several pioneering studies have demonstrated that the diversity of the gut microbiota of patients not only correlates with the occurrence of medical complications after allogeneic hematopoietic cell transplantation (alloHCT), including graft-versus-host disease (GvHD) and bloodstream infection, but also with relapse of the underlying disease.

“Given the impact of antibiotics on the gut microbiota, this raises the question of the impact of antibiotics on patients’ outcomes after alloHCT,” says Associate Professor Mallard. “In fact, in the 1970s and 1980s, studies in mice and humans established that use of antibiotics for gut decontamination was associated with an improved overall survival and a decreased incidence of GvHD. Unfortunately, subsequent control studies of gut decontamination were difficult to perform and mostly failed to demonstrate a benefit, probably because of the difficulty in achieving complete gut decontamination.”

Furthermore, the negative effects of broad-spectrum antibiotics on microbiota and patient outcomes is also well established. Associate Professor Mallard will say that new strategies must be developed to lower the impact of antibiotics on microbiota composition and patient outcomes. For example, rifaximin - an antibiotic with broad-spectrum activity and negligible intestinal resorption - has shown promising results and may offer a new opportunity for gut decontamination.

He says: “Similarly, strategies should be implemented to avoid, when it is possible, the use of antibiotics with high anti-anaerobic activity, or early antibiotic initiation before the day of the alloHCT. Finally, another response could be in the development of alternative strategies aiming at restoring microbiota diversity, in particular with the use of faecal microbiota transplantation.”