Infliximab Efficacy, TDM and Serum TNFα Levels in Pediatric HSCT Recipients With aGVHD: Prospective Observational Study

In children receiving a hematopoietic stem cell transplant (HSCT), blood levels of TNFalpha (an inflammatory cytokine) at the onset of the acute GVHD (graft-versus-host disease) could be correlated with the severity of the disease. The hypothesis is that the highest infliximab (a biologic drug against TNFalpha) could be associated with a significant reduction in TNFa levels and, subsequently, with a faster remission of the symptoms and prevention of disease progression. Moreover, a rapid drop of infliximab serum concentration, documented by therapeutic drug monitoring (TDM), could be related to the active phase of GVHD and higher production of TNFalpha. Therefore, the study is aimed at investigating whether the drop in infliximab plasma concentrations could be associated with clinical response and production of TNFalpha. HSCT children receiving infliximab to control GVHD are enrolled. Blood samples will be collected during treatment and they serve to measure drug and TNFalpha concentrations. Drug levels are analyzed by a population pharmacokinetic modeling and results are compared with plasma concentrations of TNFalfa and clinical response.

Sex

All

Maximum age

18 Years

Inclusion Criteria:

* Allogeneic HSCT recipient;
* Onset of clinical signs of acute skin, gastrointestinal or hepatic GVHD according to the Glucksberg classification;
* At least five days of steroid treatment (minimum 1 mg/kg of methylprednisone or equivalent) for systemic aGVHD without clinical or laboratory signs of response or no steroid treatment for onset of grade I-II hepatic/gastroesophageal/intestinal isolated aGVHD;
* Patients who consent for the off-label use of infliximab and data processing for research purposes based on the institutional model GECO;
* At least one dose of infliximab received during aGVHD management;
* Minimum follow-up after infliximab administration: 6 months

Exclusion Criteria:

* Follow up \< 6 months.
* Active fungal or bacterial infection with life-threatening clinical condition (shock or respiratory distress that needs mechanical ventilation)

• RESULTMaximova N, Nistico D, Riccio G, Maestro A, Barbi E, Faganel Kotnik B, Marcuzzi A, Rimondi E, Di Paolo A. Advantage of First-Line Therapeutic Drug Monitoring-Driven Use of Infliximab for Treating Acute Intestinal and Liver GVHD in Children: A Prospective, Single-Center Study. Cancers (Basel). 2023 Jul 13;15(14):3605. doi: 10.3390/cancers15143605. PMID 37509268