Aim: To evaluate the population pharmacokinetics of unbound F-Ara-A (the circulating metabolite of fludarabine) in 211 patients (age range, 0.1-63.4 years) undergoing allogeneic haematopoietic stem cell transplantation conditioning.
Methods: Total (n = 2480) and unbound (n = 1403) F-Ara-A concentrations were measured in blood samples collected at timed intervals after fludarabine doses ranging from 10 to 50 mg/m and infused over 0.42-1.5 h. A three-compartment population pharmacokinetic model was developed based on unbound plasma concentrations and used to estimate F-Ara-A unbound pharmacokinetic parameters and fraction unbound (fu). A number of covariates, including glomerular filtration rate (GFR) and post-menstrual age (PMA), were evaluated for inclusion in the model.
Results: The base population mean estimates ± relative standard error (%RSE) for unbound clearance from the central compartment (CLu) and inter-compartmental clearances (Q2u, Q3u) were 3.42 ± 3%, 6.54 ± 24% and 1.47 ± 16% L/h/70 kg, respectively. The population mean estimates (%RSE) for the unbound volume of distribution into the central (V1u) and peripheral compartments (V2u, V3u) were 9.65 ± 8%, 8.17 ± 9% and 16.4 ± 10% L/70 kg, respectively, and that for fu was 0.877 ± 1%. Covariate model development involved differentiating F-Ara-A CLu into non-renal (1.81 ± 9% L/h/70 kg) and renal components (1.02 ± 9%*GFR L/h/70 kg). A sigmoidal maturation factor was applied to renal CLu, with population mean estimates for the Hill exponent and PMA at 50% mature of 2.97 ± 4% and 69.1 ± 8% weeks, respectively.
Conclusion: Patient age and GFR are predictors of unbound F-Ara-A CLu. This has the potential to impact dose requirements. Dose individualisation by target concentration intervention will be facilitated by this model once it is externally validated.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11557628 | PMC |
| http://dx.doi.org/10.1007/s00228-024-03751-0 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Adult patients with Philadelphia chromosome positive acute lymphoblastic leukemia undergoing allogeneic hematopoietic stem cell transplantation and tyrosine kinase inhibitors: development and validation of a clinical prediction model based on cytogenetics, IKZF1 deletions and minimal residual disease.
Ann Hematol
January 2025
Bone Marrow Transplantation Center, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310000, China.
The aim of this study was to develop and validate a nomogram predicting progression-free survival (PFS) for adult patients with positive acute lymphoblastic leukemia(Ph + ALL) who have undergone allogeneic hematopoietic stem cell transplantation(allo-HSCT) and tyrosine kinase inhibitor(TKI) treatment. Data were retrospectively collected from 176 adult patients diagnosed with Ph + ALL and treated with allo-HSCT and TKIs at The First Affiliated Hospital, Zhejiang University School of Medicine, between January 2015 and May 2023. 70% of the patients were randomly assigned to the training group(n = 124) and 30% of the patients were assigned to the validation group(n = 52).
View Article and Find Full Text PDFFrailty assessment in adults undergoing allogeneic hematopoietic cell transplantation: insights from a multicenter GETH-TC study to optimize outcomes and care.
Front Immunol
January 2025
Institut Català d'Oncologia - Hospital Duran i Reynals, IDIBELL, Universitat de Barcelona, Barcelona, Spain.
Introduction: This multicenter prospective study sponsored by the (GETH-TC) explores the use of frailty assessments in allo-HCT candidates.
Methods: Frailty was measured using the HCT Frailty Scale at first consultation and HCT admission in 404 adults from 15 HCT programs in Spain. Based on the results, patients were classified into fit, pre-frail and frail categories.
Impact of TP53 alteration on allogeneic hematopoietic cell transplantation outcomes for myelodysplastic syndromes.
Bone Marrow Transplant
January 2025
Peking University People's Hospital, Peking University Institute of Hematology, National Clinical Research Center for Hematologic Disease, Research Unit of Key Technique for Diagnosis and Treatments of Hematologic Malignancies, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing, China; Collaborative Innovation Center of Hematology, Peking University, Beijing, China.
The poor outcome of TP53 alteration has been reported in myelodysplastic syndrome (MDS) patients. However, the role of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in TP53 alteration patients remains debated. Previous studies showed that TP53 mutations had no effect on the prognosis of patients with acute leukemia after haploidentical HSCT (haplo-HSCT).
View Article and Find Full Text PDFCMV Reactivation Following Allogeneic Transplantation in Children From a High-Seroprevalence Population: A Single-Center Experience in Colombia.
Pediatr Transplant
February 2025
Hospital Pablo Tobón Uribe, Medellín, Colombia.
Introduction: Cytomegalovirus (CMV) infection is a frequent complication among hematopoietic stem cell transplant (HSCT) recipients. Data regarding CMV reactivation in children in underdeveloped countries is scarce. This is especially notable considering the increasing utilization of haploidentical-related HSCT with the post-transplant cyclophosphamide platform.
View Article and Find Full Text PDFThe antibiotic de-escalation strategy in patients with multidrug-resistant bacterial colonization after allogeneic stem cell transplantation.
Front Microbiol
January 2025
BMT Unit, Azienda Ospedaliera Villa Sofia-Cervello, Palermo, Italy.
Colonization by multidrug-resistant (MDR) bacteria and related bloodstream infections (BSI) are associated with a high rate of mortality in patients with hematological malignancies after intensive chemotherapy and allogeneic stem cell transplantation (allo-SCT). In this retrospective study, we analyzed the outcomes of patients colonized with MDR bacteria (primarily carbapenem-resistant , KPC), before allo-SCT. We also investigated the feasibility and safety of an antimicrobial de-escalating approach in these patients.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!