کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
5524554 | 1546249 | 2016 | 7 صفحه PDF | دانلود رایگان |
- Maraviroc administration is feasible in pediatric allogeneic transplant recipients
- Maraviroc at a dose of ~300âmg/m2 achieves acceptable plasma levels and functional blockade of chemokine receptor type 5
- Maraviroc may be helpful in preventing acute visceral graft-versus-host disease in children with pre-existing enteropathy
Maraviroc is an allosteric small molecule antagonist of chemokine receptor type 5 (CCR5) and has been used in adult allogeneic hematopoietic stem cell transplant (HSCT) recipients to prevent acute graft-versus-host disease (GVHD) of the gastrointestinal (GI) tract and liver. The goal of this study was to establish feasibility and pharmacokinetic and pharmacodynamic profiles of maraviroc in pediatric HSCT recipients. Children ages 2 to 12 years were enrolled and maraviroc was added to standard GVHD prophylaxis, which included a calcineurin inhibitor and either steroids or mycophenolate mofetil. Maraviroc was started on day -3 and administered at a dose of approximately 300âmg/m2 orally twice daily until day +30 after stem cell infusion. On days 0 and day +10, samples for pharmacokinetic analysis were collected before the dose and 1, 2, 4, 6, 8, and 12 hours after maraviroc administration. Additional trough concentrations were collected on days +7, 14, and 21. Patients were followed until day +100 for acute GVHD. Functional blockade of CCR5 was assessed in a pharmacodynamic assay by flow cytometry. Thirteen patients, median age of 4 years (range, 2 to 11 years), were prospectively enrolled. Underlying diagnoses included a primary immune deficiency (nâ=â6), hemoglobinopathy (nâ=â4), metabolic disorder (nâ=â1), and bone marrow failure syndrome (nâ=â2). Patients received either a myeloablative preparative regimen (nâ=â7) or a reduced-intensity conditioning regimen (nâ=â6). Cyclosporine and methylprednisolone (nâ=â7) was the predominant GVHD prophylactic regimen, followed by tacrolimus and mycophenolate mofetil (nâ=â4) and tacrolimus and steroids (nâ=â2). Two formulations of maraviroc (150-mg tablets and 20-mg/mL solution) were used on study. Mean (± SD) area under the concentration-time curve from 0 to 12 hours was 4805â±â3265âhour * ng/mL on day 0 and 5917â±â4048âhour * ng/mL on day +10. Four patients developed grade 1 or 2 acute skin GVHD before day +100 and were successfully treated. Two patients developed grade 3 acute GI GVHD on days +23 and +24 after HSCT and both had discontinued maraviroc before development of GI GVHD. No adverse effects attributable to maraviroc were observed and administration by enteral tubes was well tolerated by children and accepted by parents. All evaluable patients demonstrated functional CCR5 blockade on day 0. Administration of maraviroc is feasible in most pediatric HSCT recipients with good safety and tolerability profile.
Journal: Biology of Blood and Marrow Transplantation - Volume 22, Issue 10, October 2016, Pages 1829-1835