In:
Clinical Pharmacology & Therapeutics, Wiley, Vol. 108, No. 2 ( 2020-08), p. 264-273
Abstract:
Treosulfan is given off‐label in pediatric allogeneic hematopoietic stem cell transplant. This study investigated treosulfan's pharmacokinetics (PKs), efficacy, and safety in a prospective trial. Pediatric patients ( n = 87) receiving treosulfan‐fludarabine conditioning were followed for at least 1 year posttransplant. PKs were described with a two‐compartment model. During follow‐up, 11 of 87 patients died and 12 of 87 patients had low engraftment (≤ 20% myeloid chimerism). For each increase in treosulfan area under the curve from zero to infinity (AUC (0‐∞) ) of 1,000 mg hour/L the hazard ratio (95% confidence interval) for mortality increase was 1.46 (1.23–1.74), and the hazard ratio for low engraftment was 0.61 (0.36–1.04). A cumulative AUC (0‐∞) of 4,800 mg hour/L maximized the probability of success ( 〉 20% engraftment and no mortality) at 82%. Probability of success with AUC (0‐∞) between 80% and 125% of this target were 78% and 79%. Measuring PK at the first dose and individualizing the third dose may be required in nonmalignant disease.
Type of Medium:
Online Resource
ISSN:
0009-9236
,
1532-6535
Language:
English
Publisher:
Wiley
Publication Date:
2020
detail.hit.zdb_id:
2040184-X
SSG:
15,3
Permalink