Individualized Dosage Optimization for Myeloablative Conditioning before Unrelated Cord Blood Transplantation in a Diamond–Blackfan Anemia Patient with Germline RPL11 Mutation: A Case Study

Unrelated cord blood transplantation (CBT) for Diamond–Blackfan anemia (DBA), a systemic ribosomopathy affecting the disposition of conditioning agents, has resulted in outcomes inferior to those by transplantations from matched donors. We report the experience of the pharmacokinetics-guided myeloablative unrelated CBT in a DBA patient with a germline RPL11 mutation. The conditioning consisted of individualized dosing of fludarabine (based on weight and renal function with a target area under the curve (AUC) of 17.5 mg·h/L) and busulfan (based on therapeutic drug monitoring with a target AUC of 90 mg·h/L), as well as dosing and timing of thymoglobulin (based on body weight and pre-dose lymphocyte count to target pre-CBT AUC of 30.7 AU·day/mL and post-CBT AUC of 4.3 AU·day/mL, respectively). The pharmacokinetic measures resulted in a 27.5% reduction in busulfan and a 35% increase in fludarabine, as well as an over three-fold increase in thymoglobulin dosage with the start time changed to day-9 instead of day-2 compared to regular regimens. The transplantation resulted in rapid, complete, and sustained hematopoietic engraftment. The patient is now healthy over 3 years after CBT. A pharmacokinetics-guided individualized dosing strategy for conditioning might be a feasible option to improve the outcomes of DBA patients receiving unrelated myeloablative CBT.