Medical and Pharmaceutical cooperation as a contributor to the success of pediatric allogeneic hematopoietic stem-cell transplantation (allo-HSCT): inclusion process ability via the therapeutic drug monitoring (TDM) of busulfan (Bu)
2 Service Unité d’Immuno-Hématologie et Rhumatologie Pédiatrique,
HU Necker-Enfants Malades - 149 rue de Sèvres, 75015 Paris, France
Bu is recognized as the cornerstone for HSCT conditioning regimens (CR). It has a narrow therapeutic window and exhibits large pharmacokinetic (PK) variability. Bu dosage is administered in 16 doses of 2-hr infusions and finally, 96-hr exposure to this major alkylating agent. To optimize Bu duration/intensity exposure in children undergoing HSCT, we studied the contribution of Medical and Pharmaceutical cooperation during TDM of the D1/PK1 and D9/PK2 which involves a number of actors: the Clinical Department (SC), our Laboratory Unit (UF AM) and our Preparation Unit (UF PI). This study will present both the interdepartmental cooperative work and patient benefit.
Patients and methods
50 patients [1-193 months] and [3-59 kg] were included in this single-centre prospective observational study (05/2012-02/2015). Bu was monitred by UF AM using a LC-MS/MS method following the 1st and 9th doses. After PK analysis, dosage recommendations were transmitted in real time to the SC for reassessment of the computerized prescription. The UF PI finally compound the bags in a very short time (20 min to 1 h before the next administration).
Results and Discussion
The TDM resulted in a ∑AUC1-16 (Area Under the Curve of dose 1 to 16) calculated as not significantly different from the optimal target ∑AUC (p = 0.87). For 15 patients (30%), a decision of discontinuation of Bu exposure was taken following the 2nd STP. Each couple TDM-compounding was the result of continuous cooperation between SC - UF AM - PI UF. It worth to note that SC followed pharmaceutical recommendations systematically. All actors contributed to the quality of communication, each of them working to ensure mutual understanding of roles and tasks from the initial samples to final the administration of right dosage.
TDM of Bu is a relevant to better control Bu exposure and to potentially minimize the risk of overexposure. The procedure is made possible only through sustained medico-pharmaceutical cooperation. In addition, expertise from Preparation Unit is undeniable.