Intensified Mycophenolate Mofetil Dosing and Higher Mycophenolic Acid Trough Levels Reduce Severe Acute Graft-versus-Host Disease After Double-Unit Cord Blood Transplantation
| Autor: | Richard J. O'Reilly, Marcel R.M. van den Brink, James W. Young, Marissa Lubin, Sergio Giralt, Andromachi Scaradavou, Alan M. Hanash, Doris M. Ponce, Patrick Hilden, Nancy A. Kernan, Junting Zheng, Nelly G. Adel, Melissa Pozotrigo, Susan E. Prockop, Juliet N. Barker, Sean M. Devlin, Sherry Mathew, Stephen Harnicar, Robert R. Jenq, Miguel Perales |
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| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
Adult
Male medicine.medical_specialty Cord blood transplantation Adolescent medicine.medical_treatment Graft vs Host Disease Cord Blood Stem Cell Transplantation Graft-versus-host disease Gastroenterology Mycophenolic acid Article 03 medical and health sciences 0302 clinical medicine Pharmacokinetics Internal medicine medicine Humans Dosing Child Aged Transplantation business.industry Mycophenolate mofetil Infant Immunosuppression Hematology Middle Aged Mycophenolic Acid medicine.disease 3. Good health Surgery 030220 oncology & carcinogenesis Child Preschool Hematologic Neoplasms Acute Disease Trough level Female business 030215 immunology medicine.drug |
| Popis: | Although mycophenolate mofetil (MMF) has replaced corticosteroids as immunosuppression in cord blood transplantation (CBT), optimal MMF dosing has yet to be established. We intensified MMF dosing from every 12 to every 8 hours to augment graft-versus-host disease (GVHD) prophylaxis in double-unit cord blood transplantation (dCBT) and evaluated outcomes according to the total daily MMF dose/kg in 174 dCBT recipients (median age, 39 years; range, 1 to 71) who underwent transplantation for hematologic malignancies. Recipients of an MMF dose ≤ the median (36 mg/kg/day) had an increased day 100 grade III and IV acute GVHD (aGVHD) incidence compared with patients who received >36 mg/kg/day (24% versus 8%, P = .008). Recipients of ≤ the median dose who had highly HLA allele (1 to 3 of 6) mismatched dominant units had the highest day 100 grade III and IV aGVHD incidence of 37% (P = .009). This finding was confirmed in multivariate analysis (P = .053). In 83 patients evaluated for mycophenolic acid (MPA) troughs, those with a mean week 1 and 2 trough < .5 μg/mL had an increased day 100 grade III and IV aGVHD of 26% versus 9% (P = .063), and those who received a low total daily MMF dose and had a low mean week 1 and 2 MPA trough had a 40% incidence (P = .008). Higher MMF dosing or MPA troughs had no impact on engraftment after myeloablation. This analysis supports intensified MMF dosing in milligram per kilogram per day and MPA trough level monitoring early after transplantation in dCBT recipients. |
| Databáze: | OpenAIRE |
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