Twice-daily intravenous bolus tacrolimus infusion: A safe and effective regimen for graft-versus-host disease prophylaxis.

OBJECTIVE/BACKGROUND: Among patients undergoing allogeneic hematopoietic cell transplant, continuous intravenous (IV) tacrolimus infusion is frequently used for graft-versus-host disease (GvHD) prophylaxis. Twice-daily intermittent IV tacrolimus dosing may confer safety and convenience benefits. METHODS: We performed a retrospective chart review of 66 patients who received twice-daily IV bolus tacrolimus for GvHD prophylaxis. The primary end point of the study was safety, as measured by renal toxicity. The secondary end points included mean tacrolimus serum concentrations, incidence of grades II-IV acute GvHD, electrolyte abnormalities, hyperglycemia, hypertension, and neurologic toxicity. RESULTS: There was acceptable, possibly favorable, incidence of renal toxicity (42%) and no significant difference in grades II-IV GvHD (37%), compared with published data. Mean tacrolimus blood concentrations were not affected by occurrence of renal toxicity. CONCLUSION: We conclude that administration of IV tacrolimus twice daily over 4 h may be safe and effective in preventing GvHD in allogeneic hematopoietic cell transplant.

Clinical Outcomes Using Mycophenolate and Tacrolimus for Graft-versus-Host Disease Prophylaxis in Patients Undergoing Allogeneic Stem Cell Transplant: A Single Institution Experience.

For recipients of allogeneic hematopoietic stem cell transplant (HSCT), mycophenolate mofetil (MMF) plus tacrolimus combination is mostly used in reduced-intensity (RIC), and nonmyeloablative conditioning (NMAC) whereas methotrexate and tacrolimus combination is preferred in myeloablative conditioning (MAC). We present single institution outcomes in patients undergoing allogeneic HSCT with both MAC and NMAC/RIC regimen using MMF and tacrolimus for graft-versus-host disease (GVHD) prophylaxis. Data from all adult patients who underwent allogeneic HSCT from 2007 to 2017 was collected from Data Back to Centers web-based application of Center for International Blood and Marrow Transplant Research (CIBMTR). A total of 150 patients were included with the mean age of 46.9 years. For the patients who received MAC (n=109), the cumulative incidence of grade II-IV acute GVHD at day 100 was 37%, grade II-IV acute GVHD at one year was 51%, and chronic GVHD at one year was 38%. For the patients who received NMAC/RIC (n=41), the cumulative incidence of grade II-IV acute GVHD at day 100 was 31%, grade II-IV acute GVHD at one year was 28%, and chronic GVHD at one year was 36%. This institutional analysis shows that the combination of MMF and tacrolimus yields acceptable outcomes for the prevention of acute and chronic GVHD.

Cefepime versus ticarcillin and clavulanate potassium and aztreonam for febrile neutropenia therapy in high-dose chemotherapy patients.

An open labeled randomized trial comparing the efficacy and cost of empirically applied cefepime (C) as monotherapy versus combination therapy consisting of ticarcillin and clavulanate potassium and aztreonam (T/A) was performed in febrile neutropenic patients following high-dose chemotherapy (HDC) +/- radiation, with or without peripheral blood stem cell support. Over a 28-month period, 126 patients were screened and included in the study. Using afebrile status following 3 days of therapy as a primary endpoint, both regimens produced comparable clinical response rates (C = 55% vs. T/A = 61%). Also, the use of vancomycin for resistant gram-positive infections and alteration of gram-negative infection coverage was similar in both groups (C = 40% vs. T/A = 47% and C = 29% vs. T/A = 24%). Both treatment groups had similar needs for empirical antifungal therapy (C = 25% vs. T/A = 22%). There was a postrandomization difference between the two groups in that the "C" group had a significantly higher number of allogeneic transplants and non-stem-cell-supported patients, whereas the "T/A" group had a significantly greater number of autologous peripheral blood stem cell patients (p < 0.0001). Despite this difference, the C group had a significantly lower cost ratio than the T/A group (p = 0.016). In conclusion, we have shown that C treatment of febrile neutropenic patients following HDC results in similar efficacy and lower cost when compared to T/A, despite the inclusion of higher risk patients in the C group.

Formulary management of colony-stimulating factors.

The outcome of a formulary interchange from filgrastim to sargramostim for the amelioration of neutropenia for outpatients receiving myelosuppressive chemotherapy was evaluated. The pharmacy department at the James Graham Brown Cancer Center of the University of Louisville Hospital implemented a therapeutic interchange program by following the Joint Commission on Accreditation of Healthcare Organizations performance methodology, incorporating four key elements: plan, do, check, and act. After the pharmacy and therapeutics committee agreed that filgrastim and sargramostim are therapeutically equivalent, the pharmacy initiated the interchange, with a commitment to collect outcomes data to analyze the impact of the program on patient outcomes. Inclusion criteria included patient age of > or = 18 years, the presence of solid tumors or lymphoma, and current treatment with traditional chemotherapy. Patient demographics and cycle-specific data were collected for 31 patients receiving sargramostim and 20 patients receiving filgrastim from August 2000 to July 2001. Absolute neutrophil counts (ANCs) were measured before initiating and after discontinuing colony-stimulating factors. The majority (70%) of all growth factor use was initiated within one to four days of the last chemotherapy dose. No appreciable difference was found between agents for median ANC at any measured time point. The majority of patients exceeded the target ANC of 1500 cells/mm3 at the time of growth factor discontinuation. There were no significant differences in the number of patients that had adverse effects or in the number of cycles resulting in an adverse event between groups. Sargramostim demonstrated a 21% cost savings over filgrastim ($1036 versus $1318, respectively). The formulary switch from filgrastim to sargramostim resulted in a significant cost savings for the institution without increasing incidence of adverse effects and negative outcomes associated with growth factor use.