Treatment of Multiple Myeloma With Daratumumab in a Kidney Transplant Patient.

CLINICAL FEATURES: A middle-aged man with history of kidney transplantation was diagnosed with multiple myeloma (MM); he was treated with cyclophosphamide, bortezomib, and dexamethasone (CyBorD) for induction therapy. However, a repeat bone marrow biopsy after treatment revealed 10% clonal plasma cell involvement. Given residual disease, his treatment regimen was changed to daratumumab, bortezomib, and dexamethasone in an attempt to achieve minimal residual disease. THERAPEUTIC CHALLENGE: Daratumumab was recently approved for treatment of relapsed or refractory MM; there are no data regarding the safety and effectiveness in solid organ transplant patients. SOLUTION: Our patient was treated with a daratumumab-based regimen for MM. His renal function was monitored closely along with donor-specific antibody to assess for risk of graft rejection. His renal function remained stable with minimal proteinuria and negative donor-specific antibody during the treatment course.

Pharmacists' guide to the management of organ donors after brain death.

PURPOSE: This article reviews organ donor pathophysiology as it relates to medication use with the goal of maximizing the successful procurement and transplantation of donor organs. SUMMARY: The number of patients requiring organ transplantation continues to grow, yet organ donation rates remain flat, making it critical to appropriately manage each organ donor in order to ensure viability of all transplantable organs. The care given to one organ donor is tantamount to the care of several transplant recipients. Aggressive donor management ensures that the largest number of organs can be successfully procured and improves the organs' overall quality. Hospital pharmacists are responsible for processing orders and preparing the medications outlined in donor management algorithms developed by their respective medical systems. It is important that pharmacists understand the details of the medications used in these protocols in order to critically evaluate each medication order and appropriately manage the donor. Typical medications used in organ donors after brain death include medications for blood pressure management and fluid resuscitation, medications necessary for electrolyte management, blood products, vasopressors, hormone replacement therapy, antiinfectives, anticoagulants, paralytics, and organ preservation solutions. CONCLUSION: It is essential to provide optimal pharmacotherapy for each organ donor to ensure organ recovery and donation. Typical medications used in organ donors include agents for blood pressure management and fluid resuscitation, medications necessary for electrolyte management, blood products, vasopressors, hormone replacement therapy, antiinfectives, anticoagulants, paralytics, and organ preservation solutions.

Expanding the role of pharmacists and pharmacy students in the promotion of organ donation awareness.

The gap between supply and demand for available organs has resulted in numerous deaths of patients on the transplant waiting list each year. Given the substantial public health impact of the organ shortage crisis, efforts have been focused on the use of educational interventions aimed both at the public and health care professionals to spread awareness of the disparity in organ supply and demand and ultimately improve organ donation rates. Transplant pharmacists are fundamental members of transplant multidisciplinary teams and are expected to promote organ and tissue awareness in an effort to decrease the morbidity and mortality of patients on the transplant waiting list. The role of pharmacists and pharmacy students in the promotion of organ donation awareness is expanding.

Tacrolimus trough level at discharge predicts acute rejection in moderately sensitized renal transplant recipients.

BACKGROUND: Goal tacrolimus concentrations for the prevention of rejection in sensitized renal transplant recipients are not well established. METHODS: We evaluated the association between discharge tacrolimus trough concentration and the incidence of biopsy-proven acute rejection (BPAR) in 216 moderately sensitized renal transplant recipients (negative flow crossmatch and positive donor-specific antibodies) treated with tacrolimus. RESULTS: At transplant, the mean±standard deviation (SD) peak panel-reactive antibody was 60±33 and median donor-specific antibody level was a mean fluorescence intensity of 710 (interquartile range, 328-1202). The mean±SD tacrolimus trough concentration at discharge (median postoperative day, 5; interquartile range, 4-7) was 7.6±3.7 ng/dL. Patients were divided into two groups based on a discharge tacrolimus trough concentration of 8 ng/mL. Baseline characteristics were similar between groups. Thirty-four (28.6%) of the 119 patients with a tacrolimus trough concentration less than 8 ng/mL and 19 (19.6%) of 97 patients with concentrations of 8 ng/mL or greater experienced BPAR during a median follow-up of 14±4.7 months (P=0.04). Adjusting for age, race, donor status, and peak panel-reactive antibody, a discharge tacrolimus trough concentration less than 8 ng/mL was significantly associated with a higher risk of BPAR (hazard ratio, 1.84; 95% confidence interval, 1.04-3.25; P=0.04). Serum creatinine, cytomegalovirus, BK viremia, or BK nephropathy at 1 year did not differ between groups. CONCLUSIONS: In a patient population predisposed to BPAR, discharge tacrolimus trough concentration less than 8 ng/mL was associated with a nearly two times greater risk of BPAR.

Pretransplant donor-specific anti-HLA antibodies as predictors of early allograft rejection in ABO-compatible liver transplantation.

The significance of preexisting donor-specific HLA antibodies (HLA-DSAs) for liver allograft function is unclear. Our previous studies have shown that humoral alloreactivity frequently accompanies acute cellular rejection (ACR). In the present study, we set out to determine whether pretransplant HLA-DSAs correlate with clinically significant ACR in the first 90 days after transplantation and, if so, to determine their predictive values. Class I HLA-DSAs and class II HLA-DSAs were determined by single-antigen bead flow cytometry for 113 consecutive adult transplants. A statistical analysis was performed for data from 109 consecutive patients with graft survival greater than or equal to 90 days. All patients who developed biochemical graft dysfunction underwent liver biopsy for hematoxylin-eosin and complement component 4d staining. Cox proportional hazards models and associated hazard ratios revealed a significant association of pretransplant HLA-DSAs with clinically significant ACR: this association started with a mean fluorescence intensity (MFI) as low as 300 for both class I (hazard ratio = 2.7, P < 0.01) and class II (hazard ratio = 6.0, P < 0.01). Pretransplant HLA-DSAs were associated with an increased risk of ACR: P < 0.01 for class I (42% versus 18%), P < 0.001 for class II (37% versus 7%), and P < 0.001 for either class I or II (36% versus 3%). Class I or II HLA-DSAs with an MFI ≥ 1000 had the best positive predictive value for clinically significant ACR at 46%, whereas class I or II HLA-DSAs with an MFI ≥ 300 had the best negative predictive value at 97.1%. Although our study was based on consecutive patients, it was limited by the relatively low number of single-center subjects. In conclusion, the present study indicates that pretransplant HLA-DSAs, even at low levels of allosensitization, correlate with the risk of clinically significant ACR. Our findings suggest that anti-human leukocyte antigen antibodies could serve as donor-specific markers of immunoreactivity to the liver graft.

Persistence of influenza vaccine-induced antibody in lung transplant patients and healthy individuals beyond the season.

BACKGROUND: The timing of influenza vaccination and susceptibility to re-circulating virus in the population is influenced by the persistence of seroprotection. Immunosuppressed transplant patients are known to have lower antibody response rates than healthy individuals, but acceptable antibody concentrations are achieved. The duration of this seroprotection beyond a single season has not been evaluated in either healthy or immunosuppressed populations. METHODS: Influenza antibody concentrations against viruses no longer included in the vaccine were measured in serum by hemagglutination inhibition assay annually following vaccination of 73 lung transplant participants and 27 healthy controls. Seroprotection was defined as a titer of ≥ 1:40 and was compared between groups over the measured term using Fisher's exact tests. RESULTS: Seroprotection rates for influenza A and B strains at one year following immunization were 100% for lung transplant and healthy controls. Rates at two years for the influenza A strains were 65-74% for lung transplant vs. 77-100% in healthy controls. Rates for influenza B strains two years following immunization were 27-50% for lung transplant vs. 16-38% in healthy controls. (Fisher's exact test; not significant for between group comparisons; p < 0.05 for between season comparisons) CONCLUSIONS: Vaccine-induced antibody persistence appears to be influenced more by the vaccine virus strain than the immune status of the vaccinated individuals. Seroprotection rates are high 12 mo following influenza vaccination but wane over the second year, particularly for influenza B viruses. Annual influenza immunization is indicated, even for healthy individuals and even when the vaccine viruses do not change.