scholarly journals Cancer and mTOR inhibitors in kidney transplantation recipients

PeerJ ◽  
2018 ◽  
Vol 6 ◽  
pp. e5864
Author(s):  
Chih-Chin Kao ◽  
Jia-Sin Liu ◽  
Yu-Kang Chang ◽  
Ming-Huang Lin ◽  
Yen-Chung Lin ◽  
...  
Keyword(s):  
Kidney Transplantation ◽  
De Novo ◽  
Mtor Inhibitors ◽  
Cancer Development ◽  
Cumulative Exposure ◽  
National Database ◽  
Risk Of Death ◽  
Increased Risk ◽  
De Novo Cancer ◽  
Risk Of Cancer

Background Previous studies show that mTOR inhibitors decrease the risk of cancer development after kidney transplantation. However, the effect of cumulative doses of mTOR inhibitors on cancer after kidney transplantation is not well known. Methods In the current study, patients were registered into a national database in Taiwan. Between year 2000 and 2013, 4,563 patients received kidney transplantation. They were divided into two groups, according to mTOR inhibitors usage. The cumulative dose of mTOR inhibitors was recorded. Patients were followed-up until de novo cancer development, death, or the end of 2014. Results Patients were divided into two groups: mTOR inhibitors users (study group, n = 828) and mTOR inhibitors non-users (control group, n = 3,735). The median follow-up duration was 7.8 years. The risk of de novo cancer (hazards ratio (HR) 0.80, 95% CI [0.60–1.09], p = 0.16) and risk of death (HR 1.14, 95% CI [0.82–1.60], p = 0.43) was not different between mTOR inhibitor user and non-user groups. Neither high- nor low-dose exposure to mTOR inhibitors was associated with increased risk of cancer or mortality. Analysis of cancer subtypes showed no influence by mTOR inhibitors. In addition, the cause of mortality was not significantly different between the two groups. Discussion We could not find the association of mTOR inhibitors use and risk of de novo cancer development or mortality in patients with kidney transplantation in Chinese patients. Cumulative exposure to mTOR inhibitors did not change the results.

scholarly journals De Novo Cancer Incidence after Kidney Transplantation in South Korea from 2002 to 2017

2021 ◽  
Vol 10 (16) ◽  
pp. 3530
Author(s):  
Boyeon Kim ◽  
Minjin Kang ◽  
Yoonjung Kim ◽  
Hyung Soon Lee ◽  
Banseok Kim ◽  
...  
Keyword(s):  
Kidney Transplantation ◽  
South Korea ◽  
Cancer Incidence ◽  
Proportional Hazards ◽  
De Novo ◽  
Cancer Development ◽  
National Database ◽  
Monitoring Methods ◽  
Increased Risk ◽  
Risk Of Cancer

Advances in patient care and immunosuppressive drugs have improved graft survival, resulting in an increase in kidney transplantation (KT); however, persistent immunosuppression is thought to cause late occurrence of cancer. This population-based study consisted of a total of 14,842 patients whose data from the years 2002 to 2017 were collected from the National Health Information Database in South Korea. Malignancies occurred in 7.6% of the total KT patients. Prostate and thyroid cancers were the most common in males and females, respectively. From the age-adjusted incidence analysis, Kaposi’s sarcoma showed the highest standardized incidence ratio in both male and female patients. According to the linear regression model, cancer incidence in KT recipients under immunosuppressive conditions increased by approximately 0.1% each month. Patients’ age over 39 and the use of prednisolone as an initial steroid regimen were associated with increased risk of cancer development after KT. Our regression and proportional hazards models will help clinicians to predict the approximate cancer incidence risk when monitoring KT recipients. Based on the largest available national database, screening or monitoring methods for cancer detection and prevention can be established for KT patients by considering the factors involved in cancer development.

Cancer after kidney transplantation

2015 ◽  
Author(s):  
Germaine Wong ◽  
Angela C. Webster
Keyword(s):  
Kidney Transplantation ◽  
General Population ◽  
De Novo ◽  
Lymphoproliferative Disease ◽  
Prior History ◽  
Transplant Recipients ◽  
Term Survival ◽  
Mortality And Morbidity ◽  
Increased Risk ◽  
Risk Of Cancer

Cancer is a major cause of mortality and morbidity after transplantation. The overall risk of cancer among transplant recipients is at least 2.5–3-fold greater than that of the age- and gender-matched general population. The increased risk is also type specific, and is greatest among virus-related neoplasms such as Kaposi sarcoma, post-transplant lymphoproliferative disease, and vulvovaginal cancers, with an excess risk of at least 9–20 times greater than that of the general population. Cancer prognoses are also poor in transplant recipients, with less than 10% surviving 5 years after initial diagnoses. Despite the increased cancer risk, little is known about the efficacy of treatment, the screening strategies, and the outcomes of patients with cancer and kidney transplants. Uncertainties also exist as to how the various types of modern immunosuppression impact on recipients’ overall long-term survival and quality of life. This chapter discusses the incidence and prognoses of patients with de novo cancer after transplantation, the epidemiology of donor cancer transmission, the outcomes of transplanting patients with a prior history of cancer, as well as the different approaches to cancer screening and management after kidney transplantation.

Pathophysiology of intestinal metaplasia of the stomach: emphasis on CDX2 regulation

2010 ◽  
Vol 38 (2) ◽  
pp. 358-363 ◽  
Author(s):  
Rita Barros ◽  
Vânia Camilo ◽  
Bruno Pereira ◽  
Jean-Noel Freund ◽  
Leonor David ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Helicobacter Pylori ◽  
Intestinal Metaplasia ◽  
De Novo ◽  
Current Knowledge ◽  
Regulatory Mechanisms ◽  
Cancer Development ◽  
Molecular Pathways ◽  
Neoplastic Lesion ◽  
Increased Risk

IM (intestinal metaplasia) of the stomach is a pre-neoplastic lesion that usually follows Helicobacter pylori infection and that confers increased risk for gastric cancer development. After setting the role played by CDX2 (Caudal-type homeobox 2) in the establishment of gastric IM, it became of foremost importance to unravel the regulatory mechanisms behind its de novo expression in the stomach. In the present paper, we review the basic pathology of gastric IM as well as the current knowledge on molecular pathways involved in CDX2 regulation in the gastric context.

Cancer Development and Mortality Differences in Patients with Glomerulonephritis after Renal Biopsy: A Single Center Retrospective Cohort Study

2020 ◽  
Author(s):  
Hyunjin Ryu ◽  
Kipyo Kim ◽  
Jiwon Ryu ◽  
Hyung-Eun Son ◽  
Ji-Young Ryu ◽  
...  
Keyword(s):  
Cohort Study ◽  
Renal Biopsy ◽  
Retrospective Cohort Study ◽  
Retrospective Cohort ◽  
Clinical Characteristics ◽  
De Novo ◽  
Hazard Ratio ◽  
Cancer Development ◽  
De Novo Cancer

Abstract Background: The association between glomerulonephritis (GN) and cancer has been well known for decades. However, studies evaluating long-term de novo cancer development in patients with GN are limited. This study aimed to evaluate the incidence of cancer development among patients with renal biopsy-proven GN during post-biopsy follow-up and the differences in outcomes according to cancer occurrence. Methods: We conducted a retrospective cohort study of adult patients who underwent renal biopsy at Seoul National Bundang Hospital between 2003 and 2017. After excluding 671 patients who are inappropriate for the analysis, 929 patients were included in the analysis. Data on baseline clinical characteristics, renal biopsy results, and types and doses of immunosuppressant agents used during follow-up were collected from electronic medical records. The incidence of cancer was censored on the date when the first cancer was diagnosed. We evaluated rates of mortality and end-stage renal disease (ESRD) development during follow-up. Results: During a mean follow-up period of 52.4 (range: 1.0–166.7) months, 49 subjects (5.3%) developed de novo cancer. A comparison of clinical characteristics between subjects who did and did not develop cancer revealed that cancer patients were older and had higher comorbidities and immunosuppressant use. Overall, patients with GN had an elevated standardized incidence ratio (SIR) of 7.17 (95% confidence interval (CI): 5.3–9.51) relative to the general population. In particular, the SIR was significantly higher in GNs such as membranous nephropathy (MN), IgA nephropathy, lupus nephritis, and focal segmental glomerulosclerosis. Multivariable Cox proportional hazard model adjusted for confounding variables revealed that patients with a pathologic diagnosis of MN had an increased risk of cancer development, with a hazard ratio of 2.6 [95% CI: 1.32–5.30]. Patients with MN who developed cancer had a significantly higher risk of mortality (hazard ratio: 5.95; 95% CI: 1.36–26.09, P=0.018) than those without cancer, but there was a non-significant difference in ESRD development. Conclusions: Patients with GN without concurrent cancer, particularly those with MN, have significantly higher risks of cancer development and subsequent mortality and should remain aware of the potential development of malignancy during follow-up.

scholarly journals P1761SIDE EFFECTS OF MTOR INHIBITORS DEPEND ON THE BASELINE METABOLIC STATUS OF KIDNEY TRANSPLANT RECIPIENTS

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
David Cucchiari ◽  
Alicia Molina-Andujar ◽  
Enrique Montagud-Marrahi ◽  
Jordi Rovira ◽  
Fritz Diekmann
Keyword(s):  
Kidney Transplantation ◽  
Side Effects ◽  
Kidney Transplant ◽  
De Novo ◽  
Mtor Inhibitors ◽  
Metabolic Status ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients ◽  
Post Hoc Analysis ◽  
Post Hoc

Abstract Background and Aims Biologically, the cellular activity of the mTOR complexes depends on the balance between the catabolic and the anabolic inputs. Hence, we hypothesized that the metabolic side effects of mTOR inhibitors (mTORi) in kidney transplantation depend on the baseline metabolic status of the patient. Method The analysis included all the patients that have been transplanted in our Center between June 2013 to December 2016, completed one year of follow-up and did not change medication during the first year after kidney transplantation (per-protocol population, n=298). Outcomes chosen include de novo diabetes, 1-year difference from baseline in glycated hemoglobin (HbA1c), triglycerides and total cholesterol. Kidney transplant recipients were treated either with an mTORi (either Sirolimus or Everolimus, n=134) or Mycophenolic Acid (MPA, n=164). Both drugs were always accompanied by tacrolimus and steroids. Patients were stratified according to the treatment received (mTORi versus MPA) and the baseline metabolic status (diabetes mellitus type 2 and obesity). Differences among groups were analyzed with exact Fisher test and ANOVA test with LSD post-hoc analysis. Results We observed a strong difference for 1-year change in HbA1c depending on the baseline metabolic status of the patients (P<0.001 between groups, Figure 1a). The worst results were observed for patients with baseline diabetes. Among these, obese patients treated with mTORi had the higher increase in HbA1c (3.04 ± 1.18% from baseline, P<0.01 with all groups at post-hoc analysis). De-novo diabetes was more frequent in patients taking mTORi (23.4 vs. 13.1%), albeit not significantly (P=0.100) and without differences taking into account obesity as a covariate. Triglycerides increased substantially in patients without baseline diabetes and treated with mTORi (P<0.05). Surprisingly, in diabetic patients no differences were observed in triglycerides between mTORi and MPA groups (Figure 1b). There were no differences in the increase in total cholesterol among groups (P=0.155) (Figure 1c). Conclusion We observed that the 1-year increase in HbA1c and triglycerides attributable to mTORi after kidney transplantation depends on the baseline metabolic status of the patients. We propose that the metabolic side effects of mTORi depend on the balance between anabolic and catabolic inputs of every kidney transplant recipient.

Long Term Follow Up of De Novo Use of mTOR Inhibitors (mTORi) After Kidney Transplantation.

2014 ◽  
Vol 98 ◽  
pp. 543-544 ◽  
Author(s):  
M. Paula ◽  
P. Hannun ◽  
C. Felipe ◽  
A. Ferreira ◽  
M. Cristelli ◽  
...  
Keyword(s):  
Kidney Transplantation ◽  
De Novo ◽  
Mtor Inhibitors ◽  
Long Term Follow Up

Survival Varies By Age and Histology in Classical Hodgkin Lymphoma: A Report from the Children's Oncology Group

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 24-25
Author(s):  
Justine M. Kahn ◽  
Kara M. Kelly ◽  
Qinglin Pei ◽  
Yue Wu ◽  
Debra L. Friedman ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Hodgkin Lymphoma ◽  
Cumulative Incidence ◽  
De Novo ◽  
Oncology Group ◽  
Bulky Disease ◽  
Risk Of Death ◽  
Increased Risk ◽  
Multivariable Models ◽  
Effect Of Age

Introduction While 5-year event-free (EFS) and overall survival (OS) in Hodgkin lymphoma (HL) generally exceed 85% and 95%, respectively, outcomes may not be as favorable in adolescents and young adults (15 - 39 years [y]) compared to children. Small clinical trials have reported better outcomes for pediatric but not adult patients with mixed cellularity (MC) vs. nodular sclerosing (NS) histology, suggesting the possibility of biologic differences across the age-spectrum in HL. We examined survival by age and histology in patients receiving risk-based, response-adapted therapy for de novo HL on contemporary Children's Oncology Group (COG) trials. Methods This was a pooled analysis of individual-level data from 1,907 patients enrolled on three Phase 3 COG clinical trials for treatment of low-risk (AHOD0431), intermediate risk (AHOD0031) and high-risk (AHOD0831) HL between 2002 and 2012. Histologic subgroups included MC, NS and classical HL, not-otherwise-specified (cHL, NOS). Five-year cumulative incidence of relapse, EFS and OS were compared by age group (<15 y vs. ≥15 y) in the pooled cohort, and in histologic subgroups (MC and non-MC) using the Kaplan-Meier method. Effect modification was confirmed between age and histology. Cox proportional hazards regression models were used to examine the influence of age on EFS and OS, adjusted for race/ethnicity, Ann Arbor stage, B symptoms, bulky disease, receipt of radiation therapy (RT), and the interaction between age and histology; COG study was also included in the model, given that the criteria for response adaptation differed across the trials. Results Between 2002 and 2012, N= 2155 patients 1 - 21 y enrolled on three COG trials, 1,907 (88%) of whom were included in this analysis. Mean age of the cohort was 14.6 y (± 3.5) with N= 871 (46%) <15 y and N= 1,036 (54%) ≥15 y. In total, N= 1,547 patients (81%) had NS histology, N= 108 (6%) had cHL, NOS, and N= 196 (10%) had MC histology; by age, MC histology was present in N= 66 patients (7%) ≥15 y and N= 130 patients (15%) <15 y (p< 0.01). A significantly higher proportion of those ≥15 y vs. younger had B-symptoms at diagnosis (29% vs. 21%, p< 0.01), however the presence of bulky disease did not differ by age. Finally, patients ≥15 y (vs. <15 y) were significantly more likely to receive RT as part of their treatment (72% vs. 63%, p<0.01). Survival: Median follow up was 6.9 years. In unadjusted analyses, 5-year EFS and OS were 83% and 97%, respectively. The 5-year EFS was lower for patients ≥15 y vs. <15 y (85% vs 89%, p<0.01), as was the 5-year OS (96% vs. 99%, p< 0.01). In multivariable models, age ≥15 y (vs. younger) was associated with a 1.4-fold increased risk of EFS (HR: 1.4, 95% CI: 1.1, 1.8, p< 0.01), and more than a 3-fold increased risk of death (OS: HR: 3.1, 95% CI: 1.5, 6.4, p< 0.01). The effect of age on EFS varied by histologic subgroup. Among those with non-MC histology, cumulative incidence of relapse did not significantly differ by age in unadjusted models (Figure A), however 5-year EFS was significantly worse in the older group (Figure B). In multivariable analyses, age ≥15 y (vs. younger) was associated with a 1.3-fold increased risk of EFS (HR: 1.3; 1.03 - 1.7, p= 0.03) (Table). Among patients with MC histology, age ≥15 y (vs. younger) was associated with significantly higher relapse rate (22% vs. 5%, p< 0.01) (Figure C) and significantly worse 5-year EFS (75% vs. 94%, p< 0.01) (Figure D). This remained significant in multivariable models: patients with MC histology who were ≥15 y (vs. younger) had a 3.7-fold increased risk of EFS (HR: 3.7, 95% CI: 1.6, 8.9, p< 0.01) (Table). Conclusion In patients receiving response-adapted therapy for de novo HL on contemporary COG trials, adolescents ≥15 y had worse EFS and OS compared to younger groups. The magnitude of the effect of age was higher in patients with MC disease. Although recent pediatric trials in HL have indicated better survival for some children with MC histology, alternative approaches or novel therapies should be considered for older adolescents with MC disease, whose outcomes appear more like adults. Disclosures No relevant conflicts of interest to declare.

A Multicentre, Double-Blind, Randomized, Phase 2 Trial Comparing Pegfilgrastim with Filgrastim as an Adjunct to Chemotherapy for Acute Myeloid Leukaemia (AML).

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 866-866 ◽  
Author(s):  
Alberto Bosi ◽  
Jeffrey Szer ◽  
Jeannine Kassis ◽  
Jorge Sierra ◽  
Claire Desborough ◽  
...  
Keyword(s):  
Median Time ◽  
Induction Chemotherapy ◽  
De Novo ◽  
Severe Neutropenia ◽  
Single Administration ◽  
Serious Adverse Events ◽  
Treatment Groups ◽  
Risk Of Death ◽  
Increased Risk ◽  
Significant Difference

Abstract BACKGROUND: Heil et al (Blood ‘97) demonstrated that the duration of neutropenia and its clinical consequences following induction chemotherapy for AML were significantly reduced by the addition of filgrastim, with no increased risk of death, second malignancy or relapse (ASH ‘99). A single injection of pegfilgrastim has been shown to be comparable to daily injections of filgrastim in the management of chemotherapy-induced neutropenia. The primary aim of this trial was to estimate the difference in time to recovery from severe neutropenia (SN, ANC < 0.5 x109/L) in the first induction chemotherapy cycle (Induction 1) in AML subjects treated with pegfilgrastim or filgrastim. METHODS: Subjects with de novo AML received 1 or 2 courses of induction chemotherapy (idarubicin 12mg/m2 IV days 1–3, cytarabine 100mg/m2 IV 12 hourly days 1–7 [IA 3+7]) then, if in remission, consolidation chemotherapy (cytarabine 2 [subjects < 55 years] or 3g/m2 [subjects ≥ 55 years] IV 12 hourly days 1, 3, 5). Subjects received either single administration 6μg pegfilgrastim or daily 5μg/kg filgrastim starting 24 hours after completion of chemotherapy until neutrophil recovery. Time to recovery from SN was defined as the number of days from the first day of chemotherapy until the first of two ANC consecutive values after the nadir that were ≥ 0.5 x 109/L whereas duration of SN was defined as the total number of days during the cycle with an ANC < 0.5 x 109/L. RESULTS: Of 84 subjects randomised into the study, 83 received study drug (42 pegfilgrastim, 41 filgrastim). The treatment groups were generally well balanced for demographics and baseline characteristics. The median time to recovery from SN (ANC < 0.5 x109/L) in Induction 1 was 22 days in both treatment groups (95% CI for treatment difference: −1.9, 1.9). There was also no statistically significant difference in the median duration of SN between the 2 groups (21 days pegfilgrastim, 20 days filgrastim). Subjects in the filgrastim group required a median of 16 daily injections compared to a single administration of pegfilgrastim in the second group. Median serum concentration of pegfilgrastim in Induction 1 remained above clinically relevant concentrations until 21 days after the start of chemotherapy, results that are consistent with the neutrophil-mediated clearance of pegfilgrastim. The incidence of serious adverse events was comparable between the 2 groups except for infectious complications, which were higher in the filgrastim group (5 subjects [12%] pegfilgrastim versus 9 subjects [22%] filgrastim). CONCLUSION: In the setting of the first cycle of IA 3+7 induction chemotherapy in AML patients, once per cycle administration of 6 mg pegfilgrastim or daily administration of 5mg/kg filgrastim result in similar median time to recovery to ANC ≥ 0.5 x109/L. Pegfilgrastim is safe and well tolerated in this subject population.

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