scholarly journals FO048EFFECT OF INITIAL IMMUNOSUPPRESSION ON LONG TERM KIDNEY TRANSPLANT OUTCOME IN IMMUNOLOGICAL LOW RISK PATIENTS

2018 ◽  
Vol 33 (suppl_1) ◽  
pp. i39-i39 ◽  
Author(s):  
Laura Michielsen ◽  
Arjan van Zuilen ◽  
Bram Wisse ◽  
Marianne Verhaar ◽  
Elena Kamburova ◽  
...  
Keyword(s):  
Kidney Transplant ◽  
Low Risk ◽  
Transplant Outcome ◽  
Risk Patients

Effect of initial immunosuppression on long-term kidney transplant outcome in immunological low-risk patients

2018 ◽  
Vol 34 (8) ◽  
pp. 1417-1422 ◽  
Author(s):  
Laura A Michielsen ◽  
Arjan D van Zuilen ◽  
Marianne C Verhaar ◽  
Bram W Wisse ◽  
Elena G Kamburova ◽  
...  
Keyword(s):  
Kidney Transplant ◽  
Graft Survival ◽  
Human Leukocyte ◽  
Low Risk ◽  
Kidney Graft ◽  
Free Survival ◽  
Leukocyte Antigen ◽  
Single Antigen ◽  
Risk Patients

Abstract Background Few studies have evaluated the effect of different immunosuppressive strategies on long-term kidney transplant outcomes. Moreover, as they were usually based on historical data, it was not possible to account for the presence of pretransplant donor-specific human-leukocyte antigen antibodies (DSA), a currently recognized risk marker for impaired graft survival. The aim of this study was to evaluate to what extent frequently used initial immunosuppressive therapies increase graft survival in immunological low-risk patients. Methods We performed an analysis on the PROCARE cohort, a Dutch multicentre study including all transplantations performed in the Netherlands between 1995 and 2005 with available pretransplant serum (n = 4724). All sera were assessed for the presence of DSA by a luminex single-antigen bead assay. Patients with a previous kidney transplantation, pretransplant DSA or receiving induction therapy were excluded from the analysis. Results Three regimes were used in over 200 patients: cyclosporine (CsA)/prednisolone (Pred) (n = 542), CsA/mycophenolate mofetil (MMF)/Pred (n = 857) and tacrolimus (TAC)/MMF/Pred (n = 811). Covariate-adjusted analysis revealed no significant differences in 10-year death-censored graft survival between patients on TAC/MMF/Pred therapy (79%) compared with patients on CsA/MMF/Pred (82%, P = 0.88) or CsA/Pred (79%, P = 0.21). However, 1-year rejection-free survival censored for death and failure unrelated to rejection was significantly higher for TAC/MMF/Pred (81%) when compared with CsA/MMF/Pred (67%, P < 0.0001) and CsA/Pred (64%, P < 0.0001). Conclusion These results suggest that in immunological low-risk patients excellent long-term kidney graft survival can be achieved irrespective of the type of initial immunosuppressive therapy (CsA or TAC; with or without MMF), despite differences in 1-year rejection-free survival.

Elevated CK-MB values after routine angioplasty predicts worse long-term prognosis in low-risk patients

2010 ◽  
Vol 44 (2) ◽  
pp. 69-75 ◽  
Author(s):  
Kjell Vikenes ◽  
Tor Melberg ◽  
Mikael Farstad ◽  
Jan Erik Nordrehaug
Keyword(s):  
Low Risk ◽  
Risk Patients ◽  
Long Term Prognosis

scholarly journals Long-term impact of catheter ablation on arrhythmia burden in low-risk patients with paroxysmal atrial fibrillation: The CLOSE to CURE study

Heart Rhythm ◽  
2020 ◽  
Vol 17 (4) ◽  
pp. 535-543 ◽  
Author(s):  
Mattias Duytschaever ◽  
Jan De Pooter ◽  
Anthony Demolder ◽  
Milad El Haddad ◽  
Thomas Phlips ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Catheter Ablation ◽  
Paroxysmal Atrial Fibrillation ◽  
Low Risk ◽  
Risk Patients ◽  
Long Term Impact

Long-Term Follow-Up of the Italian Trial of Interferon- Versus Conventional Chemotherapy in Chronic Myeloid Leukemia

Blood ◽  
1998 ◽  
Vol 92 (5) ◽  
pp. 1541-1548 ◽  
Author(s):  
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Chronic Phase ◽  
Low Risk ◽  
Long Term Effects ◽  
Conventional Chemotherapy ◽  
Risk Patients ◽  
Cytogenetic Remission ◽  
Ifn Treatment

Abstract Several prospective randomized studies have shown that the treatment of chronic myeloid leukemia with interferon- (IFN-) prolongs the survival by comparison with conventional chemotherapy. However, although IFN- can induce cytogenetic responses, true complete remissions are rarely achieved and information on the long-term effects of IFN- treatment is limited. For that purpose, we updated and analyzed a prospective comparative trial of IFN- and conventional chemotherapy that was initiated in 1986. The first analysis of the trial was already published, and showed a survival advantage for IFN- (N Engl J Med 12:820, 1994). The observation period of living patients now ranges between 95 and 129 months and we examined the long-term effects of IFN- treatment, always by comparison with conventional chemotherapy and according to the intention-to-treat principle. The patients who were submitted to allogeneic bone marrow transplantation (BMT) in chronic phase (38 of 322 or 12%) were censored at the date of BMT. Seventy-three of the original 284 nontransplanted patients were alive, 56 (30%) in the IFN- arm and 17 (18%) in the chemotherapy arm. Forty-one patients overall (14%) were still receiving IFN-. In the IFN- arm 9 patients were in continuous complete cytogenetic remission and 11 were in major or minor cytogenetic remission. Median and 10-year survival of low-risk patients were 104 months (95% CI, 85 to 127 months) and 47% (95% CI, 36% to 59%) in IFN- arm versus 64 months (95% CI, 49 to 98 months) and 30% (95% CI, 16% to 44%) in chemotherapy arm (P = .03). Median and ten-year survival of non–low-risk patients were 69 months (95% CI, 56 to 76 months) and 16% (95% CI, 8% to 24%) in IFN- arm versus 46 months (95% CI, 39 to 61 months) and 5% (95% CI, 0% to 11%) in chemotherapy arm (P = .006). A low Sokal’s risk, hematologic response, and cytogenetic response were associated with a longer survival. No major or unusual side effects were recorded after the 5th year of IFN- treatment. Fourteen patients died in chronic phase, 9 (4%) in IFN- arm and 5 (5%) in chemotherapy arm, mainly of cardiovascular accidents (6 cases) and of other cancers (5 cases). We conclude that a policy of chronic treatment with IFN- maintained a significant survival advantage over conventional chemotherapy on a long-term basis and irrespective of the risk. However, the great majority of the long-term survivors were in the low-risk group. The question of treatment discontinuation was not addressed in this study. © 1998 by The American Society of Hematology.

EFFECT OF HISTOLOGICAL DAMAGE ON LONG-TERM KIDNEY TRANSPLANT OUTCOME

2001 ◽  
Vol 71 (4) ◽  
pp. 515-523 ◽  
Author(s):  
Brian J. Nankivell ◽  
Carol A. Fenton-Lee ◽  
Dirk R.J . Kuypers ◽  
Elaine Cheung ◽  
Richard D.M. Allen ◽  
...  
Keyword(s):  
Kidney Transplant ◽  
Transplant Outcome ◽  
Histological Damage

Long-term opioid users with chronic noncancer pain: Assessment of opioid abuse risk and relationship with healthcare resource use

2018 ◽  
Vol 14 (2) ◽  
pp. 131 ◽  
Author(s):  
Anna D. Coutinho, BPharm, PhD ◽  
Kavita Gandhi, BPharm, MS ◽  
Rupali M. Fuldeore, BAMS, MS ◽  
Pamela B. Landsman-Blumberg, MPH, DrPH ◽  
Sanjay Gandhi, PhD
Keyword(s):  
Risk Factors ◽  
At Risk ◽  
Opioid Abuse ◽  
Low Risk ◽  
Chronic Noncancer Pain ◽  
Cart Analysis ◽  
Risk Patients ◽  
Noncancer Pain ◽  
Abuse Risk

Objective: Identify opioid abuse risk factors among chronic noncancer pain (CNCP) patients receiving long-term opioid therapy and assess healthcare resource use (HRU) among patients at elevated abuse risk.Design: Data were obtained from an integrated administrative claims database. Classification and Regression Tree (CART) analysis identified risk factors potentially predictive of opioid abuse, which were used to classify the overall population into cohorts defined by levels of abuse risk. Multivariable logistic regression compared HRU across risk cohorts.Setting: Retrospective cohort study.Patients, participants: 21,072 patients aged ≥18 years diagnosed with ≥1 of 5 types of CNCP and a prescription for Schedule II or III/IV opioid medication used long-term (≥90 days).Main outcome measures: (1) Opioid abuse risk factors; (2) HRU differences between risk cohorts.Results: CART analysis identified four groups at elevated opioid abuse risk defined by three factors (age, daily opioid dose, and total days’ supply of opioids); sensitivity: 70.3 percent, specificity: 74.1 percent, and positive predictive value: 5.6 percent. The analysis results were used to classify patients into low-risk (72.5 percent), at-risk (25.4 percent), and opioid-abuser (2.2 percent) cohorts. In multivariable analysis, emergency department (ED) use was higher among at-risk vs low-risk patients (odds ratio [OR]: 1.14; p < 0.05); hospitalization and ED visits were higher for opioid-abusers vs low-risk patients (OR: 2.33 and 2.14, respectively; p < 0.05).Conclusions: This study identifies a subpopulation of CNCP patients at risk of opioid abuse. However, limited sensitivity and specificity of criteria defining this subpopulation reinforce the importance of physician discretion in patient-level treatment decisions.

scholarly journals Strong Predictors of Chromosomal Aberrations and Myeloid Neoplasia Following Immunosuppression Therapy for Severe Aplastic Anemia: A Retrospective Cohort Study

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 601-601
Author(s):  
Emma M. Groarke ◽  
Bhavisha A. Patel ◽  
Ruba Shalhoub ◽  
Fernanda Gutierrez-Rodrigues ◽  
Parth Desai ◽  
...  
Keyword(s):  
High Risk ◽  
Clonal Evolution ◽  
Low Risk ◽  
Competing Risk ◽  
Long Term Outcomes ◽  
Risk Patients ◽  
Risk Evolution ◽  
Pre Treatment ◽  
Myeloid Neoplasia

Abstract Introduction: Immune aplastic anemia (AA) is effectively treated with either immunosuppressive treatment (IST) or allogeneic hematopoietic stem cell transplant (HSCT). Clonal evolution remains the most feared long-term complication after IST. We investigated predictor factors, genetic characteristics, and long-term outcomes of patients who developed either secondary myeloid neoplasia or isolated chromosomal abnormalities without morphologic dysplasia after immunosuppression. Methods: All patients with severe AA treated at the NIH Clinical Center with IST from 1989-2020 who underwent clonal evolution were categorized as "high-risk" (overt myeloid neoplasia, or isolated chromosome 7 abnormality / complex cytogenetics) or "low-risk" (isolated chromosome abnormalities without overt myeloid neoplasia or dysplasia; isolated chromosome 7 abnormality or complex cytogenetics were characterized as high-risk). Univariable analysis was performed using the Fine-Gray competing risk regression model using death as a competing risk to determine predictors of clonal evolution. Classification and regression tree analysis of time to clonal evolution was performed on continuous baseline variables to partition the data based on the best categorical cutoff. Long term outcomes assessed included overall survival (OS) and HSCT. Error corrected next-generation sequencing (ECS) was used to assess for pathogenic somatic variants in known myeloid cancer genes in clonal evolvers both at time of evolution and in serial samples prior when available. Results: Of 659 patients with severe AA included in this study, 95 developed clonal evolution: 59 high-risk and 36 low-risk. Age &gt;48 years at diagnosis and pre-treatment ANC &gt;0.87x10 9/L were strong predictors of high-risk clonal evolution. High-risk clonal evolution was increased in patients aged &gt;48 years, with cumulative incidence (CI) of 13.9% by 5 years compared to patients aged &lt;48 years of 3.8% by 5 years (p&lt;0.001). Baseline ANC &gt;0.87 x10 9/L (independent of age) predicted an even higher risk of evolution; CI for high-risk evolution was 17% by 5 years (p&lt;0.001). Combined high ANC and older age (&gt;48 years) were prognostic of the greatest risk of high-risk evolution, with a hazard ratio (HR) of 5.51; conversely, ANC &lt;0.87 x10 9/L and age &lt;48 years was protective, with HR 0.32. High-risk clonal evolution was not significantly increased by use of eltrombopag with IST versus IST only (p=0.3), but there was an increase when all clonal evolution was considered (p=0.02). Overall survival in high-risk evolution was 35% at 5 years and in low-risk evolution was 84% (p&lt;0.001). Patients with high-risk evolution who underwent HSCT (n=26) had better OS compared to those treated with chemotherapy or supportive care (p=0.005). RUNX1 (13 variants in 8 [35%] patients) and ASXL1 (13 variants in 10 [43%] patients) were the most frequent mutated genes at time of clonal evolution in high-risk patients, and BCOR/L1 (14 variants in 8 [32%] patients) was the most frequently mutated in the low-risk group. Longitudinal data were available in five high-risk and eight low-risk patients. Three of five high-risk patients had acquisition or expansion of RUNX1 clones at evolution. Small RUNX1 variants were present in two patients as early as three years prior to high-risk evolution. Splicing factor genes and RUNX1 somatic variants were detected exclusively in the high-risk group; DNMT3A, BCOR/L1 and ASXL1 gene mutations were present in both groups. Conclusion: Age and pre-treatment ANC strongly predict high-risk clonal evolution in AA patients after IST and may be used determine at-risk patients for long term follow-up. Outcomes in patients with low-risk evolution are favorable but poor in high-risk evolution without HSCT. The clonal landscape differs between high-risk and low-risk evolution; MDS-associated genetic mutations are enriched in high-risk evolution, in particular RUNX1. Further study of the role of RUNX1 in high-risk clonal evolvers may give insight into leukemogenesis in AA. Figure 1: Cumulative incidence (CI) of clonal evolution since immunosuppression with death treated as competing risk. (A) CI for development of all clonal evolution in patients &gt;37 years (B) and high-risk clonal evolution in patients &gt;48 years (C) CI for development of all clonal evolution when baseline ANC &gt;0.87x10 9/L and (D) high-risk clonal evolution when baseline ANC &gt;0.87x10 9/L. Figure 1 Figure 1. Disclosures Young: Novartis: Research Funding.

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