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EBMT 2022 Annual Meeting - Paediatrics Day

Paediatric Diseases Working Party (PDWP)

Paediatrics Day - Tuesday, March 22, 09:00 - 17:15 CET

Paed1 Paediatrics Diseases Working Party Session, Tuesday, March 22, 09:00 - 10:15 CET, Virtual Hall 4 

In the session Paed1-03 the talk ‘Towards Predictable Immune Reconstitution after Transplantation’ will be delivered by Professor Jaap Jan Boelens, Chief Attending Physician for the Pediatric TCT Service, Memorial Sloan Kettering Cancer Center, New York, USA.

He will discuss that haematopoietic cell transplantation (HCT) is a curative treatment option for specific ‘hard-to-treat’ malignant and non-malignant diseases. Success of the procedure depends mainly on disease control and treatment-related complications. Pharmacotherapy plays a major role in HCT, and significantly impacts the outcomes, in particular because of the unpredictable impact on immune reconstitution.

“Increasing evidence suggests individualised dosing will improve outcomes after HCT; both higher efficacy and lower toxicity, mainly driven by better predictable immune reconstitution. Pharmacokinetics (PK) are found to be highly variable, and these highly variable drug exposures are found to have huge impact on outcomes,” explains Prof Boelens.

For agents like busulfan, thymoglobuline (ATG) and fludarabine the varied drug exposures found after standard weight or BSA-based dosing have a significant impact on survival. For example, transplantation-related mortality (TRM) has been found to be related to over-exposure of thymoglobuline and/or fludarabine. Overexposure impacted immune reconstitution dramatically, resulting in more difficult to treat infections and subsequently higher TRM.

Prof Boelens concludes: ”Individualised dosing of these drugs, using population PK models, will result in a better predictable drug exposure and subsequently in better predictable immune reconstitution. This was also recently shown in a prospective clinical trial (PARACHUTE; Admiraal et al, The Lancet Haematology 2022). Further individualizing of therapy, considering the PK of agents used in HCT, will make HCT significantly safer and more effective and will result in improved survival.”

AM22 Paediatric Sessions Jaap Jan Boelens
Jaap Jan Boelens