Alemtuzumab Induction Versus Conventional Immunosuppression in Heart Transplant Recipients

2019 ◽  
Vol 24 (5) ◽  
pp. 435-441 ◽  
Author(s):  
Stormi E. Gale ◽  
Bharath Ravichandran ◽  
Van-Khue Ton ◽  
Si Pham ◽  
Brent N. Reed
Keyword(s):  
Renal Function ◽  
Heart Transplantation ◽  
Induction Therapy ◽  
Standard Therapy ◽  
Infectious Complications ◽  
Acute Cellular Rejection ◽  
Orthotopic Heart Transplantation ◽  
Antibody Mediated Rejection ◽  
End Point ◽  
Cellular Rejection

The use of alemtuzumab for induction therapy in orthotopic heart transplantation remains controversial, despite its observed benefits in other transplant populations. This study aimed to evaluate whether alemtuzumab conferred a lower risk of rejection while reducing toxicities commonly attributed to standard immunosuppression in orthotopic heart transplantation. We included adult patients who underwent orthotopic heart transplantation and received induction therapy with alemtuzumab (n = 26) or standard immunosuppression (n = 26). The primary end point was freedom from grade ≥2 rejection at 12 months. Baseline characteristics were similar between the groups with the exception of poorer renal function in the alemtuzumab group ( P < .05). The primary end point of freedom from grade ≥2 rejection at 12 months was not different between alemtuzumab and standard therapy (76.9% vs 96.2%, P = .077), likely due to similarities in the rates of antibody-mediated rejection in the 2 groups. However, grade ≥2 acute cellular rejection was considerably lower with alemtuzumab (0% vs 19.2%, P = .02), as was acute cellular rejection of any severity (50% vs 7.7%, P = .004). Deterioration in renal function was significantly greater among patients receiving standard therapy as evidenced by decreases in glomerular filtration rate (−25.6 vs −9.2 mL/min, P = .032). No differences in hematologic or infectious complications were observed. In conclusion, alemtuzumab reduced several important rejection-related outcomes while ameliorating the toxicities associated with standard immunosuppression therapy, making it a promising agent for induction in orthotopic heart transplantation.

scholarly journals Three-Dimensional Self-Navigated T2 Mapping for the Detection of Acute Cellular Rejection After Orthotopic Heart Transplantation

2017 ◽  
Vol 3 (4) ◽  
pp. e149 ◽  
Author(s):  
Ruud B. van Heeswijk ◽  
Davide Piccini ◽  
Piergiorgio Tozzi ◽  
Samuel Rotman ◽  
Philippe Meyer ◽  
...  
Keyword(s):  
Heart Transplantation ◽  
T2 Mapping ◽  
Three Dimensional ◽  
Acute Cellular Rejection ◽  
Orthotopic Heart Transplantation ◽  
Cellular Rejection

A Single-Center Experience of the Optimal Initial Immunosuppressive Strategy for Preventing Early Acute Cellular Rejection in Orthotopic Heart Transplantation Associated With Renal Dysfunction

2019 ◽  
Vol 29 (4) ◽  
pp. 327-334
Author(s):  
Juan Mundisugih ◽  
Himavan Fernando ◽  
Peter Bergin ◽  
James Hare ◽  
David Kaye ◽  
...  
Keyword(s):  
Acute Rejection ◽  
Heart Transplantation ◽  
Renal Dysfunction ◽  
Standard Therapy ◽  
Calcineurin Inhibitor ◽  
Calcineurin Inhibitors ◽  
Acute Cellular Rejection ◽  
Rank Test ◽  
Post Transplant ◽  
Cellular Rejection

Background: Renal dysfunction is a common complication following heart transplantation that may be worsened by the early initiation of calcineurin inhibitors. Antithymocyte globulin (ATG) or basiliximab has been used to delay or avoid calcineurin inhibitors. The most effective strategy for preventing early acute cellular rejection in this context is uncertain. Methods: We retrospectively reviewed all heart transplant cases between January 2012 and June 2017. The standard therapy consisted of mycophenolate mofetil, prednisolone, and tacrolimus. In patients at high risk of post-transplant renal dysfunction, an early calcineurin inhibitor-free regimen with basiliximab and/or ATG was used. Patients were assigned to cohorts based on the initial immunosuppressive strategy. The primary end point was the freedom rate of acute cellular rejection within 4 weeks post-transplant. Results: Of 93 cases, 21 patients received standard therapy, 64 patients received an initial calcineurin inhibitor-free regimen with basiliximab, and 8 patients received ATG and basiliximab. Freedom from acute rejection was greater in the ATG plus basiliximab group (all rejection free), compared to 40 (63%) of 64 patients treated with basiliximab and 10 (48%) of 21 patients treated with standard therapy ( P < .05, log rank test). In patients treated with basiliximab, early administration (<24 hours) was associated with a higher freedom from acute rejection compared to ≥24 hours, (72% vs 29%, P < .05). Conclusions: The combination of ATG and basiliximab was more effective in preventing acute cellular rejection. In those patients treated with basiliximab, rejection rates were no worse than standard therapy; however, it was only effective when administered within 24 hours.

P5455Serum microRNA-181a-5p expression pattern correlates with acute cellular rejection in heart transplantation

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
I Constanso ◽  
L Nunez ◽  
M Hermida-Prieto ◽  
G M Marron-Linares ◽  
E Alvarez-Lopez ◽  
...  
Keyword(s):  
Heart Transplantation ◽  
Expression Pattern ◽  
Expression Patterns ◽  
False Negative ◽  
Acute Cellular Rejection ◽  
P Value ◽  
Serum Samples ◽  
Relative Expression ◽  
Antibody Mediated Rejection ◽  
Cellular Rejection

Abstract Background Acute Cellular Rejection (ACR) remains a major complication in heart transplantation (HT). Since 1970, endomyocardial biopsy (EMB) has been the gold standard for ACR early detection. However, this invasive procedure has several limitations such as risk of complications, interobserver variability, false negative results and high cost. Therefore, a new non-invasive ACR biomarker is needed. Potential candidates could be microRNAs (miRs), small regulatory RNAs whose serum expression profiling could be modified in ACR patients. The aim of this study is the identification of differentially serum miRs expression patterns in ACR after HT. Methods Among HT performed in our Hospital (2013–2018), we selected patients with following criteria: i) “0R → 2R → 0R” EMB pattern for ACR (0R=no ACR, 2R=moderate ACR); ii) no antibody mediated rejection; iii) serum collected the same day as the EMBs. The 3 serum samples per patient matched in time with EMB were called “0Rs1 → 2Rs2 → 0Rs3”. In each of these serum samples, 179 miRs expression profile according manufacturer's instructions were analysed. Global Mean (GM) method was used to normalize our results expressed as miRs relative expression [2(–ΔCq)]. Expression pattern was defined as a 2 steps process: a significative rise (0Rs1 → 2Rs2) followed by a significative fall (2Rs2 → 0Rs3), or vice versa, in miR expression. Analysis of differences between 3 groups were calculated using one-way ANOVA with matched data and post-hoc Tukey test. ROC curve was generated for selected miRNA. A two-sided p<0.05 was considered statistically significant. Results 21 patients and their serum “0Rs1 → 2Rs2 → 0Rs3” samples were included in the study. Among 179 miRs analysed, 5 miRs showed significative difference between 0Rs1 and 2Rs2, 3 miRs were over-expressed (miR-181a-5p, miR-339-3p, let-7f-5p) and 2 under-expressed (miR-505-3p, miR-2110). Only miR-181a-5p met significative difference between 2Rs2 and 0Rs3 showing a statistical significative rise/fall pattern. Serum miR-181a-5p ROC analysis demonstrated significant discrimination between biopsy proven ACR from no-ACR biopsy, AUC=0.692 (p=0.0335). Differentially expressed miRs Mean relative expression 2(–ΔCq) (95% CI) Adjusted p-value (ANOVA) AUC (95% CI) 0Rs1 2Rs2 0Rs3 0Rs1 vs 2Rs2 2Rs2 vs 0Rs3 0Rs1 vs 0Rs3 miR-181–5p 0.80 (0.60–1.02) 1.11 (0.90–1.31) 0.86 (0.71–1.01) 0.0194 0.0225 NS 0.692 (0.529–0,855) Relative Expression 2(–ΔCq) and AUC expressed as mean (95% Confident Interval). NS: not significative. Conclusion Our findings suggest miR-181a-5p as a novel serological biomarker for detecting ACR after HT. After this preliminary discovery phase, miR-181a-5p is currently in a new validation phase to demonstrate its diagnostic performance. Acknowledgement/Funding This work was supported by a grant from isciii (PI15/02224) and it is part of the of the “CIBERCV”. Co-financed with FEDER Funds

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