CASE PRESENTATION: A 59-year-old man of Chinese ethnicity presented to our hematology unit with headache, lethargy, and exertional dyspnea for the past 1 month. He underwent an uneventful cadaveric renal transplant 20 years ago for chronic glomerulonephritis-induced end-stage renal disease. He had been on long-term immunosuppressants since then consisting of orally administered prednisolone 10 mg daily and orally administered cyclosporine A 50 mg twice daily. On examination, he was pale with a palpable liver and spleen. He had a functioning renal graft. Marrow flow cytometry confirmed T-prolymphocytic leukemia with lymphocytes expressing CD2, CD3, CD7, CD52, and TCL-1. His human T-cell lymphotropic virus and Epstein-Barr virus serology and deoxyribonucleic acid (DNA) were negative. He was treated with one cycle of cyclophosphamide, doxorubicin, vincristine, and prednisone chemotherapy to which he failed to respond. In view of his renal allograft, he was not suitable for alemtuzumab due to the risk of nephrotoxicity. He was given orally administered venetoclax but he died on day 17 due to severe auto tumor lysis syndrome.
CONCLUSION: The place of immunophenotyping in the diagnosis and treatment of this disorder is of significant importance. More research needs to be carried out to further comprehend the pathophysiology and treatment modalities for this disorder.
METHODS: The MEDLINE and EMBASE databases, as well as the reference lists of all articles, were searched to identify population PK models of tacrolimus developed from adult transplant recipients published from the inception of the databases to 29 February 2020.
RESULTS: Of the 69 studies identified, 55% were developed from kidney transplant recipients and 30% from liver transplant recipients. Most studies (91%) investigated the oral immediate-release formulation of tacrolimus. Few studies (17%) explained the effect of drug-drug interactions on tacrolimus PK. Only 35% of the studies performed an external evaluation to assess the generalizability of the models. Studies related variability in tacrolimus whole blood clearance among transplant recipients to either cytochrome P450 (CYP) 3A5 genotype (41%), days post-transplant (30%), or hematocrit (29%). Variability in the central volume of distribution was mainly explained by body weight (20% of studies).
CONCLUSION: The effect of clinically significant drug-drug interactions and different formulations and brands of tacrolimus should be considered for any future tacrolimus population PK model development. Further work is required to assess the generalizability of existing models and identify key factors that influence both initial and maintenance doses of tacrolimus, particularly in heart and lung transplant recipients.
METHODOLOGY: This is a retrospective cohort study recruiting all kidney transplant recipients in South Australia from January 2010 till December 2018. Following that, the incidence of blood transfusion within one week post-operatively were traced (transfusion group). The outcomes were compared with all other transplant recipients (non-transfusion group). Recipient's demographic, donor characteristics and immunological risk profiles were obtained from the transplant unit database, while the biopsy report, history of blood transfusion, latest serum creatinine and follow-up status was gathered from the electronic medical system (OASIS). The HLA-DSA and HLA-Ab results were collected from the NOMS database. Finally, the survival data were merged with the Australia and New Zealand Dialysis and Transplant (ANZDATA) Registry for South Australia recipients graft survival.
RESULTS: A total of 699 patients were eligible for analysis. The mean age was 50.64 ± 13.23 years old. There were more elderly (>65 years old) and females who needed transfusion. The majority had glomerulonephritis as the primary disease. There was no statistical difference in donor characteristics, cold ischemic time and immunological risk between the transfusion and non-transfusion group. There was no difference in the development of de novo HLA-DSA, HLA-Ab and rejection episodes between the group and the results were consistent in a model adjusted for all potential confounders. Median graft survival in days between the transfusion vs non-transfusion group was 1845 IQR (961,2430) and 1250 IQR (672,2013).
CONCLUSION: Blood transfusion under strong immunosuppressive cover within a one-week post-operative period is safe with no significant association with the development of de novo HLA-DSA, HLA-Ab or clinical rejection.
METHODOLOGY: All sera for AT1R-Ab were collected at the University Malaya Medical Centre (UMMC), Kuala Lumpur, Malaysia. The sera were centrifuged and kept refrigerated at -80 °C before being transported to the South Australian Transplantation and Immunogenetics Laboratory (SATIS). Enzyme-linked immunosorbent assay kit (One Lambda) was used for the detection of AT1R-Ab, and it was performed according to the manufacturer's instructions. The level of >17.1 U/mL was considered to be AT1R-Ab positive; 10.0-17.1 U/mL at risk, and <10.0 U/mL negative.
RESULTS: A total of 115 samples were collected from 99 patients pre and post-kidney transplant recipients. From the pre-transplant sera (n = 68) 17.7% were positive, 35.3% were at risk and 47.0% were negative. The positive AT1R-Ab cohort were relatively younger, with a mean age of 34.7 ± 8.3 years old and statistically significant, with a p-value of 0.028. Among the sera that were tested positive, 19.0% were from the Chinese ethnicity, 6.7% from Malay and 16.7% from Indian. There was no difference in the rejection episodes, persistent or de novo HLA-DSA, and graft function between the group (AT1R-Ab negative vs AT1R-Ab at risk and positive) and the results were consistent in a model adjusted for all potential confounders.
CONCLUSION: The prevalence of positive (>17.1 U/mL) pre-transplant AT1R-Ab was 17.7% and 35.3% were at risk (10.0-17.1 U/mL) in our pre-transplant cohort.
AIM AND METHODS: This study used microcosting methods to determine the cost and health outcomes of living and deceased donor kidney transplantation in adult and pediatric recipients. The perspective used was from the Ministry of Health Malaysia. Cost-effectiveness measures were cost per life year (LY) and cost per quality-adjusted LYs. The time horizon was the lifetime of the transplant recipient from transplant to death.
RESULTS: Records of 206 KT recipients (118 adults and 88 children) were obtained for microcosting. In adults, discounted cost per LY was US $8609(Malaysian Ringgit [RM]29 482) and US $13 209(RM45 234) for living-donor kidney transplant (LKT) and deceased donor kidney transplant (DKT), respectively, whereas in children, it was US $10 485(RM35 905) and US $14 985(RM51 317), respectively. Cost per quality-adjusted LY in adults was US $8826 (RM30 224) for LKT and US $13 592(RM46 546) for DKT. Total lifetime discounted costs of adult transplants were US $119 702 (RM409 921) for LKT, US $147 152 (RM503 922) for DKT. Total costs for pediatric transplants were US $154 841(RM530 252) and US $159 313(RM545 566) for the 2 categories respectively.
CONCLUSIONS: Both LKT and DKT are economically favorable for Malaysian adult and pediatric patients with ESRD and result in improvement in quality of life.