How can donors with a previous malignancy be evaluated?
Explore the source record for details and available documents.
Humans↗
Biomedical subjects
Rita R Alloway
Publications and source records attributed to Rita R Alloway.
Body weight alterations under early corticosteroid withdrawal and chronic corticosteroid therapy with modern immunosuppression.
BACKGROUND: Weight gain is a known complication of corticosteroid maintenance therapy. The purpose of the present study was to compare patterns of weight gain under chronic corticosteroid therapy (CCST) with that observed under early (i.e., within 7 days posttransplant) corticosteroid withdrawal (CSWD) in renal-transplant recipients. METHODS: Renal-transplant recipients who underwent early CSWD under four prospective, institutional review board-approved clinical trials were compared with a historic control group of patients receiving maintenance CCST. RESULTS: One hundred sixty-nine patients with early CSWD were compared with 132 patients who received CCST. Mean population weight gain was significantly higher in CCST patients at 3, 6, and 12 months posttransplant. Race influenced weight gain because white CSWD patients demonstrated greater reductions in weight gain compared with African-American patients. Sex also influenced weight gain: women demonstrated a greater benefit from CSWD than did men. Corticosteroid rejection therapy in CSWD patients completely restored weight gain because these patients showed weight gains similar to the CCST group. Finally, pretransplant body mass index (BMI) also influenced weight gain because patients who were overweight (BMI 25-30) or obese (BMI>30) demonstrated a greater reduction in weight gain with CSWD than did patients of normal weight (BMI<25). CONCLUSIONS: Early CSWD minimizes weight gain in renal-transplant recipients. Women, whites, and patients with high pretransplant BMI had greater reductions in weight gain with early CSWD.
Adrenal Cortex Hormones↗
United network for organ sharing publication on scientific registry of transplant recipients central nervous system donor cancer transmission data.
Explore the source record for details and available documents.
Central Nervous System Neoplasms↗
African-American renal transplant recipients benefit from early corticosteroid withdrawal under modern immunosuppression.
African-Americans (AAs) have historically been considered high-risk renal transplant recipients due to increased rejection rates and reduced long-term graft survival. As a result, AAs are often excluded from corticosteroid withdrawal (CSWD) protocols. Modern immunosuppression has reduced rejections and improved graft survival in AAs and may allow successful CSWD. Outcomes in 56 AAs were compared to 56 non-AAs. All patients were enrolled in one of four early CSWD protocols. Results are reported as AA versus non-AA. Acute rejection at 1-year was 23% and 18%; (p = NS); creatinine clearance at 1-year was 75 versus 80 mL/min (p = NS); patient and graft survival was 96% versus 98% and 91% versus 91%; (p = NS). AAs benefit from early CSWD with significantly improved blood pressure, LDL < 130 mg/dL and HDL > 45 mg/dL at 1-year, post-transplant diabetes of 8.7%, and mean weight change at 1-year of 4.8 +/- 7.2 kg. In conclusion, early CSWD in AAs is associated with acceptable rejection rates, excellent patient and graft survival, and improved cardiovascular risk, indicating that the risks and benefits of early CSWD are similar between AAs and non-AAs. Additional follow-up is needed to determine long-term renal function, graft survival, and cardiovascular risk in AAs with early CSWD.
Adrenal Cortex Hormones↗
Analysis of factors that influence survival with post-transplant lymphoproliferative disorder in renal transplant recipients: the Israel Penn International Transplant Tumor Registry experience.
Significant mortality is associated with post-transplant lymphoproliferative disorder (PTLD) in kidney transplant recipients (KTX). Univariate/multivariate risk factor survival analysis of US PTLD KTX reported to Israel Penn International Transplant Tumor Registry from November 1968 to January 2000 was performed. PTLD presented 18 (median) (range 1-310) months in 402 KTX. Death rates were greater for those diagnosed within 6 months (64%) versus beyond 6 months (54%, p = 0.04). No differences in death risk for gender, race, immunosuppression, EBV, B or T cell positivity were identified. Death risk increased for multiple versus single sites (73% vs. 53%, hazards ratio (HR) 1.4). A 1-year increase in age increased HR for death by 2%. Surgery was associated with increased survival (55% vs. 0% without surgery) (p < 0.0001). Patients with allograft involvement, treated with transplant nephrectomy alone (n = 20), had 80% survival versus 53% without allograft removal (n = 15) (p < 0.001). Overall survival was 69% for allograft involvement alone versus 36% for other organ involvement plus allograft (n = 19 alive) (p < 0.0001). Death risk was greater for multiple site PTLD and increasing age, and risks were additive. Univariate analysis identified increased death risk for those not receiving surgery, particularly allograft involvement alone.
Graft Rejection↗
Multivariate analysis of risk factors for acute rejection in early corticosteroid cessation regimens under modern immunosuppression.
The purpose of this study was to define risk factors for acute rejection with early corticosteroid withdrawal (CSWD; within 7 days posttransplant) in renal transplantation. Data from prospective, IRB-approved early CSWD trials were analyzed. Overall acute rejection rate in 308 patients was 17.1%. Acute rejection rates and observed risks (OR) in patients with individual risk factors were: repeat transplants 38.6%; current PRA >25%; 29.4%; African Americans 23.5%; delayed graft function (DGF) 26.1%; HLA DR mismatches >0 17.9%; female gender 19.7%; Thymoglobulin induction 15.3%; type 1 diabetes 30.8%; type 2 diabetes 11.1%; deceased donor recipients 21%; and living donor recipients 14%. Logistic regression analysis provided the following risks (OR) for acute rejection: repeat transplant 2.51; current PRA > 25% 1.53; African Americans 1.47; DGF 1.58; HLA DR mismatches > 0 1.61; female gender 1.43; Thymoglobulin induction 0.61; type 1 diabetes 2.23, type 2 diabetes 0.5, deceased donor recipients 1.11, and living donor recipients 0.9. Risk factors for acute rejection under early corticosteroid withdrawal are similar to those previously defined under chronic corticosteroid therapy. These observations provide implications for future CSWD trials including: use of T cell depleting antibody induction therapy (thymoglobulin) to reduce acute rejection risk, 2) enrollment stratification for high risk groups, and 3) modified immunosuppression for high risk groups.
Acute Disease↗
Can immunonutrients reduce rejection rates in African Americans?
OBJECTIVES: African-American kidney allograft recipients have higher rates of rejection than do white patients. This study was performed to determine whether the use of immunonutrients may reduce the incidence of rejection in African Americans. MATERIALS AND METHODS: Two studies have been done at our institution that demonstrate that immunonutrients can reduce the incidence of rejection, calcineurin inhibitor toxicity, and cardiovascular risk factors. The data were analyzed to determine whether or not a preferential benefit exists for race. RESULTS: Twenty-four African-American patients received supplements and 28 did not. One patient (4.2%) who had received supplements had a rejection episode in the first year compared with 7 patients (25%) who did not receive supplements (P < .011). This compares with our rejection rate of 25% (14/56) for African Americans on other protocols without concurrent immunonutrients (P < .003). CONCLUSIONS: Immunonutrients appear to have a preferential beneficial response in reducing rejection in African-American patients. A randomized, prospective, clinical trial is warranted to further elucidate these results.
Black or African American↗
Experience with 274 cardiac transplant recipients with posttransplant lymphoproliferative disorder: a report from the Israel Penn International Transplant Tumor Registry.
BACKGROUND: Posttransplant lymphoproliferative disorder (PTLD) is a life-threatening complication that occurs in a small but significant minority of solid organ transplant recipients. Published experiences with PTLD in cardiac transplant recipients are limited to relatively small single-center reports. METHODS: This report presents experience with 274 cases of PTLD in cardiac transplant recipients reported to the Israel Penn International Transplant Tumor Registry (IPITTR). RESULTS: PTLD carried an ominous prognosis: Kaplan Meier survival after PTLD diagnosis was 45%, 33%, 30%, and 13%, respectively, at 1, 3, 5, and 10 years. Common causes of death included: PTLD, cardiovascular collapse, and infection; all occurred at a median of less than 6 months. Risk of death from cardiovascular collapse secondary to immunosuppression withdrawal was substantial (28%), indicating that a fine balance exists between death from PTLD and from sudden cardiac death due to acute rejection. PTLD therapy in the majority of patients consisted of combination therapy (49%). Survival in patients receiving immunosuppression minimization (ISM) alone was 32%, with ISM plus other therapy was 27%, and with other therapies not containing ISM was 11% (P < 0.01). CONCLUSION: PTLD in cardiac transplant recipients is associated with low long-term survival rates. Analysis of PTLD therapies and outcomes suggest that immunosuppression minimization, when applied, improves survival. However, risk of sudden death may mitigate the positive effect of ISM. This observation has important implications for ISM in PTLD therapy in cardiac transplant recipients. Carefully designed prospective studies are needed to evaluate the positive and negative effects of ISM in cardiac transplant recipients with PTLD.
Adult↗
Recurrence risk after organ transplantation in patients with a history of Hodgkin disease or non-Hodgkin lymphoma.
This study defines the incidence and recurrence risk of Hodgkin disease (HD) and non-Hodgkin lymphoma (NHL) after organ transplant. Patients from the United States with a history of HD or NHL before organ transplantation reported to the Israel Penn International Transplant Tumor Registry from 1968 to 2001 were analyzed. A total of 91 patients underwent organ transplantation with a lymphoma history: HD (38 patients) and NHL (53 patients). Median disease-free interval pretransplant was 99 (range 0-459.1) months, and median follow-up posttransplant was 25.7 (0.4-131.1) months. Ten patients were excluded from further analysis because of lack of follow-up information (n=9) or they never achieved remission (n=1). Recurrence incidence was 8 of 81 patients (10%) (HD=3/34 [9%] vs. NHL=5/47 [11%]). Gender, race, allograft type and source, age at lymphoma diagnosis, and immunosuppression did not influence recurrence. Patients with less than a 2-year period between diagnosis and transplant seem to be at increased risk of relapse. Median disease-free interval before transplant was longer for patients without recurrence (115 vs. 30.2 months, P=0.24), but was not statistically significant. Median time to recurrence posttransplant was 18.7 (range 1.9-82.2) months (HD=3.7 vs. NHL 23.6 months, P=0.10). Survival after recurrence was poor (HD [1/3] and NHL [1/5], median survival 6.8 [range 0-22.1] months). There is no difference in recurrence rates for HD and NHL. The outcome for recurrent lymphoma is poor. The low risk of recurrence (10%) indicates that preexisting HD and NHL need not be an absolute contraindication to transplantation.
Adolescent↗
Characteristics and survival patterns of solid organ transplant patients developing de novo colon and rectal cancer.
PURPOSE: Immunosuppression used in transplantation is associated with an increased incidence of various cancers. Although the incidence of colorectal cancer in transplant patients seems to be equal to nontransplant population, the effects of immunosuppression on patients who develop colorectal cancer are not well defined. The purpose of this study was to define the characteristics and survival patterns of transplant patients developing de novo colorectal cancer. METHODS: The Israel Penn International Transplant Tumor Registry was queried for patients with colorectal cancer. Analysis included patient demographics, age at transplantation and colorectal cancer diagnosis, tumor stage, and survival. Age and survival rates were compared to United States population-based colorectal cancer statistics using the National Cancer Institute Surveillance Epidemiology and End Results database. RESULTS: A total of 150 transplant patients with de novo colorectal cancer were identified: 93 kidney, 29 heart, 27 liver, and 1 lung. Mean age at transplantation was 53 years. Age at transplantation and colorectal cancer diagnosis was not significant for gender, race, or stage of disease. Compared to National Cancer Institute Surveillance Epidemiology and End Results database, transplantation patients had a younger mean age at colorectal cancer diagnosis (58 vs. 70 years; P < 0.001), and a worse five-year survival (overall, 44 vs. 62 percent, P < 0.001; Dukes A and B, 74 vs. 90 percent, P < 0.001; Dukes C, 20 vs. 66 percent, P < 0.001; and Dukes D, 0 vs. 9 percent, P = 0.08). CONCLUSIONS: Transplant patients develop colorectal cancer at a younger age and exhibit worse five-year survival rates than the general population. These data suggest that chronic immunosuppression results in a more aggressive tumor biology. Frequent posttransplantation colorectal cancer screening program may be warranted.
Aged↗
Polyomavirus nephropathy in kidney transplantation.
Polyomavirus nephropathy has become an important complication in kidney transplantation, with a prevalence of 1% to 8%. Unfortunately, the risk factors for polyomavirus nephropathy and renal allograft loss are not well defined. The definitive diagnosis is made through assessment of a kidney transplant biopsy. Recently, noninvasive urine and serum markers have been used to assist in polyomavirus nephropathy diagnosis and monitoring. Primary treatment is immunosuppression reduction, but must be balanced with the risks of rejection. No antiviral treatments for polyomavirus nephropathy have been approved by the Food and Drug Administration. Although cidofovir has shown in vitro activity against murine polyomaviruses, and has been effective in some patients, it is associated with significant nephrotoxicity. Graft loss due to polyomavirus nephropathy should not be a contraindication to retransplantation; however, experience is limited. This review presents potential risk factors, screening, diagnostic and monitoring methods, therapeutic management, and retransplantation experience for polyomavirus nephropathy.
Antiviral Agents↗
Posttransplant malignancy.
In the past few decades, great advances have been made in the field of solid-organ transplantation. A greater understanding of immune system function, the development of modern immunosuppression, and advancements in surgical technique have led to marked improvements in both recipient and graft survivals, as well as recipients' quality of life. However, improved survival rates have also led to prolonged exposure to chronic immunosuppression, which increases the risk for the development of posttransplant malignancies. In addition, older transplant candidates are being considered, carrying with them the increased likelihood of preexisting malignancy. Consequently, the potential risk of posttransplant malignancy must be considered. Moreover, as long-term transplant survivors continue to age, posttransplant malignancies will be seen more frequently. This review presents the more commonly encountered posttransplant malignancies and the measures that are currently being utilized to prevent and treat them.
Adult↗
Donor transmitted malignancies.
Early experiences in transplantation, which pre-dated brain death laws, utilized organs from donors with active malignancies. The use of organs from such donors occasionally resulted in the transmission of malignancy from the donor to an unknowing recipient. Over a period of three decades, Israel Penn, M. D. catalogued some two hundred and fifty cases of organs transplanted from donors with a history of malignancy; carefully examining each reported case for tumor histology, donor risk factors, method of tumor presentation and recipient outcome. Some recipients never developed malignancies, while others were less fortunate, developing cancers that were suspicious for donor origin. The evolution of transplantation has resulted in improved patient survival, which in turn has led to an increased demand for organ transplantation. Unfortunately, the supply of organs available for transplantation has failed to keep pace with the demand, with the worldwide deficit growing annually. In an effort to bridge the widening gap, utilization of older and more marginal donors has been suggested. However, use of older donors is accompanied by the likelihood that a significant proportion may have undiagnosed malignancies. Multiple transplant programs have considered the use of donors with tumors of non-malignant or even low-grade malignant histology, most often involving the central nervous system (CNS). According to a survey from the United Network for Organ Sharing (UNOS), central nervous system malignancies are among the most commonly identified malignancies found in potential donors. This study examines the distribution of potential donor transmitted malignancies reported to the Israel Penn International Transplant Tumor Registry. The incidence of tumor transmission is examined in the overall group as well as among individual histologies. We also seek to identify specific factors associated with the risk of malignancy transmission from donor to recipient, in an effort to minimize future transmission of donor tumors to unwitting recipients. The study is based on voluntary registry data, which some argue can be criticized for a lack of true incidence data. In reality, however, this data may provide a more accurate insight since it is based on transmissions from high-risk donors rather than from the general population.
Humans↗
Basic and clinical research in polyomavirus nephropathy.
Over the last decade, polyomavirus nephropathy (PVN) has emerged as an important cause of renal allograft dysfunction and graft loss. PVN occurs with a prevalence of 1%-8% in renal transplant recipients and is most commonly reported within the first 12 months posttransplant. The human polyomavirus, BK virus, is thought to be the primary etiologic agent of PVN. Risk factors for PVN are not well defined and are most likely a result of a complex interaction between multiple donor and recipient factors. Definitive diagnosis of PVN is made through histological assessment of a renal allograft biopsy. Recent studies have also evaluated noninvasive urine and serum markers for screening of BK virus replication and as adjunct tools in PVN diagnosis and monitoring. The principal treatment for PVN is immunosuppression reduction, but this must be balanced against the risks of rejection. If rejection occurs concurrently with PVN, a brief increase in immunosuppression to treat the rejection episode followed by a subsequent reduction in immunosuppression is recommended. No antiviral treatments for PVN have been approved by the Food and Drug Administration. Although the antiviral drug cidofovir has shown in vitro activity against murine polyomaviruses, and has been effective in some patients, it is associated with significant nephrotoxicity. Small series of patients treated with leflunomide and intravenous immune globulin therapy for PVN have also recently been reported. Retransplantation after graft loss due to PVN is feasible, but experience is limited. Current research is focusing on identifying PVN risk factors, refining screening, diagnostic and monitoring methods, and developing therapy for prophylaxis and treatment of PVN with the goals of decreasing the prevalence of PVN and improving allograft outcomes in renal transplant recipients diagnosed with PVN. This review will present recent advances in basic and clinical research related to PVN and renal transplantation.
Humans↗
Two-dose daclizumab regimen in simultaneous kidney-pancreas transplant recipients: primary endpoint analysis of a multicenter, randomized study.
BACKGROUND: Controversy exists about the optimal immunosuppressive regimen in simultaneous kidney-pancreas transplant (SKPT) recipients. This study determined the safety and efficacy of two dosing regimens of daclizumab compared with no antibody induction in SKPT recipients receiving tacrolimus, mycophenolate mofetil, and steroids. METHODS: A total of 297 SKPT patients were enrolled in this prospective, multicenter, randomized, open-label study. The patients were randomized into three groups: daclizumab 1 mg/kg per dose every 14 days for five doses (group I, n=107), daclizumab 2 mg/kg per dose every 14 days for two doses (group II, n=112), and no antibody induction (group III, n=78). All patients received tacrolimus, mycophenolate mofetil, and steroids as maintenance immunosuppression. RESULTS: Demographic and transplant characteristics were similar among the groups. At 6 months, there were no differences in patient, kidney, and pancreas graft survival rates among the three groups. The probability of either kidney or pancreas allograft rejection at 6 months was 21%, 17%, and 32% in groups I, II, and III, respectively (P=0.042). The median time to first acute rejection of either the kidney or pancreas was 23 days in group I, 44 days in group II, and 20 days in group III (group I vs. II, P=0.078; group II vs. III, P=0.016). At 6 months, the actuarial event-free survival (no acute rejection, allograft loss, or death) rates were 66%, 77%, and 56% in groups I, II, and III, respectively (group I vs. III, P=0.119; group II vs. III, P=0.002). There were no differences in the incidence of serious adverse events including infectious complications among the groups. All three groups demonstrate excellent kidney and pancreas function at 6 months. CONCLUSIONS: Daclizumab is safe and effective in reducing the incidence of acute rejection in SKPT recipients compared with no antibody induction. Moreover, the two-dose regimen of daclizumab (2 mg/kg on days 0 and 14) compares favorably with the standard five-dose regimen.
Adult↗
MALToma: a Helicobacter pylori-associated malignancy in transplant patients: a report from the Israel Penn International Transplant Tumor Registry with a review of published literature.
BACKGROUND: Mucosa-associated lymphoid tissue lymphoma (MALToma) is a Helicobacter pylori-related tumor of B-cell origin, the malignant potential for which remains to be defined in immunosuppressed patients. METHODS: Review of the Israel Penn International Transplant Tumor Registry identified six cases of gastric MALToma. Patient demographics, management, and outcomes were compared and published literature was reviewed. RESULTS: MALToma developed in six transplant recipients (three kidney, two heart, one kidney-pancreas). All were treated with immunosuppression minimization and therapy for H. pylori, resulting in disease regression in five patients. One patient developed progression to high-grade MALToma despite documented H. pylori eradication, required surgery and chemotherapy, and died, with significant disease at autopsy. CONCLUSIONS: Treatment of MALToma with immunosuppression minimization and anti-H. pylori therapy results in a majority of patients becoming disease free. Observation of malignant degeneration into an aggressive, high-grade lymphoma in one patient indicates the malignant potential. Diligent follow-up of these patients with endoscopy and biopsy is therefore indicated.
Adult↗
Report of the American Society of Transplantation conference on immunosuppressive drugs and the use of generic immunosuppressants.
Considerable economic and health-related costs are associated with the life-long maintenance immunosuppressive therapy required to prevent transplant rejection. Generic medications have the potential of providing equivalent therapeutic efficacy at a lower economic cost. In 2001, the American Society of Transplantation invited experts to review the data and issues associated with the approval and use of generic immunosuppressants. A summary of that meeting is reported here. The generic medication approval process has been in effect for more than 30 years. All marketed generic cyclosporin formulations have met FDA criteria demonstrating bioequivalence in healthy subjects, and some were also tested in transplant recipients. Most participants agreed that generic narrow therapeutic index immunosuppressive agents provide adequate de novo immunosuppression in low-risk transplant recipients. However, some participants expressed concern regarding the currently unquantified risk that may be associated with switching immunosuppressive agents under uncontrolled circumstances. There was broad agreement among the participants that generic medications should be clearly labeled and distinguishable from innovator drugs, and that patients should be educated to inform their physicians of any switch to or among generic alternatives. There was also strong support in favor of requiring studies to demonstrate bioequivalence in potentially at-risk patient populations, specifically African-Americans and pediatric patients.
Cyclosporine↗
The effect of CYP3A5 and MDR1 polymorphic expression on cyclosporine oral disposition in renal transplant patients.
Variability in CYP3A (CYP3A4/5) and P-glycoprotein (human MDR1 gene product) activity underlies interindividual differences in oral cyclosporine (CsA) bioavailability. Racial differences in polymorphic expression of CYP3A5 and MDR1 may explain observed interracial variability in oral bioavailability. Our objective was to evaluate the effect of CYP3A5 and MDR1 polymorphic expression on CsA oral disposition. Steady-state plasma concentration profiles (n = 19) were sampled in renal transplant recipients receiving concentration-adjusted CsA maintenance therapy. CsA plasma concentrations were measured by fluorescence polarization immunoassay. CYP3A5 and MDR1 genotypes were determined by real-time polymerase chain reaction. Noncompartmental pharmacokinetic analysis and nonlinear mixed-effects modeling (NONMEM) were performed to assess the effect of genotype on CsA pharmacokinetics. MDR1 C3435T genotype was identified as the best predictor of CsA systemic exposure. CsA oral clearance was significantly higher in subjects who carried at least one 3435T allele compared to homozygous wild-type individuals (40.0 +/- 2.2 vs. 26.4 +/- 3.1 L/h, p = 0.007). MDR1 C3435T genotype accounted for 43% of the interindividual variability of CsA oral clearance in the study population after accounting for interoccasion variability. The authors were unable to independently assess whether CYP3A5 correlated with any CsA pharmacokinetic parameter since all CYP3A5 nonexpressors were also 3435T allele carriers. MDR1 3435T allele carriers have enhanced oral clearance compared to individuals with the CC genotype. The frequency of the 3435T allele is lower in African Americans compared to Caucasians. Thus, the MDR1 C3435T genotype offers a potential mechanistic basis to explain interracial differences in CsA oral bioavailability. Further studies are needed to explore the relationship between CYP3A5 and MDR1 genotype and phenotype.
Adult↗