Factors Affecting Day-to-Day Variations in Tacrolimus Concentration among Children and Young Adults Undergoing Allogeneic Hematopoietic Stem Cell Transplantation

• Published in: Transplantation and cellular therapy 2023-04, Vol.29 (4), p.270.e1-270.e8
• Main Authors: Maruyama, Yuta, Maejima, Yuya, Hirabayashi, Koichi, Morokawa, Hirokazu, Okura, Eri, Saito, Shoji, Nakazawa, Yozo
• Format: Article
• Language: English
• Subjects: Adult; Body weight; Carcinoma, Renal Cell - complications; Carcinoma, Renal Cell - drug therapy; Child; Fever; Graft vs Host Disease - drug therapy; Graft vs Host Disease - prevention & control; Hematocrit; Hematopoietic Stem Cell Transplantation - adverse effects; Humans; Kidney Neoplasms - complications; Kidney Neoplasms - drug therapy; Methotrexate - therapeutic use; Retrospective Studies; Tacrolimus - therapeutic use; Tacrolimus concentration; Transfusion; Young Adult
• ISSN: 2666-6367; 2666-6367
• DOI: 10.1016/j.jtct.2023.01.014

•Hematocrit variations correlate with variations in tacrolimus concentration.•Red blood cell concentrate transfusion is associated with an increase in tacrolimus concentration.•Platelet concentrate transfusion is associated with a decrease in tacrolimus concentration.•Low body weight is associated with sharp variations in tacrolimus concentration.•Fever variably affects tacrolimus concentration depending on the type of fever. Tacrolimus is widely used as prophylaxis for graft-versus-host disease (GVHD) in allogeneic stem cell transplantation (allo-HSCT). It has a narrow therapeutic index range; high tacrolimus concentrations are associated with toxicity, whereas low concentrations are associated with an increased risk of GVHD. Although dose adjustments based on therapeutic drug monitoring are performed, unexpected large variations in tacrolimus concentration are sometimes encountered. The available evidence suggests that the factors affecting tacrolimus concentration are not fully understood. This study was aimed primarily at investigating the factors affecting day-to-day variations in tacrolimus concentration in children and young adults who received continuous tacrolimus infusion after allo-HSCT. The secondary objective was to identify the factors causing large variations (>20%) in tacrolimus concentrations. This retrospective cohort study comprised 123 consecutive pediatric and young adult patients (age 7 ng/mL and day 28 post-allo-HSCT. Subsequently, information for the subsequent 24 hours was collected along with the tacrolimus concentrations and hematocrit values. Tacrolimus concentration was determined using whole blood samples. Tacrolimus concentrations were significantly higher in patients who received red blood cell concentrate (RCC) transfusions (P < .0001) and methotrexate (P = .0162), patients with persistent fever (P = .0056), and patients with a decline in fever (P = .0003). In contrast, tacrolimus concentrations were significantly lower in patients who received platelet concentrate (PC) transfusions (P < .0001), who redeveloped