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Digital archive of theses discussed at the University of Pisa

 

Thesis etd-10172022-174725


Thesis type
Tesi di specializzazione (4 anni)
Author
BALDUCCI, SERENA
URN
etd-10172022-174725
Thesis title
Tyrosine Kinase Inhibitors plasma concentration in Chronic Myeloid Leukemia: a new horizon in patient-tailored therapy.
Department
MEDICINA CLINICA E SPERIMENTALE
Course of study
EMATOLOGIA
Supervisors
relatore Prof.ssa Galimberti, Sara
correlatore Prof. Di Paolo, Antonello
Keywords
  • drug plasma concentration monitoring
  • ponatinib
  • tyrosine kinase inhibitors
  • chronic myeloid leukemia
Graduation session start date
14/11/2022
Availability
Withheld
Release date
14/11/2092
Summary
Tyrosine Kinase Inhibitors (TKIs) treatment deeply changed Chronic Myeloid Leukemia (CML) natural history with a favorable long-term outcome in more than 90% of patients. Among those drugs, 3rd generation TKI Ponatinib allowed to obtain satisfying responses in patients who failed multiple therapeutic approaches or in case of multi-resistant T315I point-mutation.
Nevertheless, TKIs - especially Ponatinib - are burdened by long-term multi-systemic toxicities as well as by an increased risk of cardiovascular events; those side effects are frequently dose-dependant and in recent years many studies tried to develop guidelines for TKIs dose-reduction to find a new balance between efficacy and toxicity.
In our research, we tested TKIs concentration in CML patients’ plasma samples to analyze both intra- and inter-subject variability; pharmacological findings has been then correlated to clinical data - CML response and side effects - to develop a new tool helping physicians in choices regarding TKIs switch or dose modifications.
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