Author: C.-H. Wang ; Y.-S. Chen ; S.-C. Huang ; I.-H. Wu ; S.-S. Wang ; Y.-J. Wang ; N.-H. Chi ; C.-T. Shun ; J.-T. Tsai ; C.-I. Tsao ; H.-Y. Yu ; N.-K. Chou

BACKGROUNDMalignancy is the leading cause of death in Taiwan. The risk of malignancy is higher in heart transplant recipients than in the general population. We reviewed the malignancy incidence among the patients who underwent heart transplantation (HT) at the National Taiwan University Hospital (NTUH) during the past 28 years. We found that the incidence of malignancy is low in Taiwan and that the pattern of malignancy is different from that in the Western population.METHODSFrom July 1987 to March 2015, 518 patients underwent HT at NTUH. Forty-four patients who died within 1 month after transplantation were excluded from this study. Thus, a total of 476 patients were enrolled in this study. There were 393 male and 83 female patients, with a mean age of 45 years at transplantation. The major indications for HT were dilated cardiomyopathy (52%) and ischemic cardiomyopathy (33%). After HT, all patients received triple immunosuppressive therapy, including a calcineurin inhibitor (cyclosporine or tacrolimus), cell-cycle inhibitor (azathioprine, mycophenolate mofetil, or everolimus), and steroid. After 1995, induction with rabbit anti-human thymocyte globulin was routinely performed. Survival was estimated by means of the Kaplan-Meier method.RESULTSTwenty-seven patients without pre-transplantation malignancy developed malignancies after HT. The median survival time (MST) of these 27 HT patients was 76.8 months. After malignancy was diagnosed, the overall MST was 20.7 months. The 3- and 5-year overall survival rates were 44% and 27%, respectively. Twenty-one patients (77.8%) died, 10 of them because of cancer. The most common malignancy was non-Hodgkin lymphoma (n = 6), followed by skin cancer (including 2 keratoacanthomas, 2 squamous cell carcinomas, and 1 basal cell carcinoma; n = 5) and lung squamous cell carcinoma (n = 3). The univariate analysis identified cancer stage (P = .044) and comorbidity (P = .002) as factors associated with poor malignancy survival. In the multivariate analysis, comorbidity was an independent prognostic factor for greater risk of death because of post-transplantation malignancy (P = .002).CONCLUSIONSIn Taiwan, the risk of malignancy after HT is low (5.7%), as is the incidence of skin cancer. The most common malignancy was non-Hodgkin lymphoma, followed by skin cancer and lung cancer. Comorbidity was an independent factor for overall survival in cancer patients who previously underwent HT.

01 Jul 2013·DrugsQ1 · MEDICINE

Adverse Effects of Immunosuppressant Drugs upon Airway Epithelial Cell and Mucociliary Clearance: Implications for Lung Transplant Recipients

Q1 · MEDICINE

Review

Author: Rogerio Pazetti ; Fabio Biscegli Jatene ; Paulo Manuel Pêgo-Fernandes

Optimal post-transplantation immunosuppression is critical to the survival of the graft and the patient after lung transplantation. Immunosuppressant agents target various aspects of the immune system to maximize graft tolerance while minimizing medication toxicities and side effects. The vast majority of patients receive maintenance immunosuppressive therapy consisting of a triple-drug regimen including a calcineurin inhibitor, a cell cycle inhibitor and a corticosteroid. Although these immunosuppressant drugs are frequently used after transplantation and to control inflammatory processes, limited data are available with regard to their effects on cells other than those from the immunological system. Notably, the airway epithelial cell is of interest because it may contribute to development of bronchiolitis obliterans through production of pro-inflammatory cytokines. This review focuses the current armamentarium of immunosuppressant drugs used after lung transplantation and their main side effects upon airway epithelial cells and mucociliary clearance.

15 Sep 2005·American Journal of Respiratory and Critical Care MedicineQ1 · MEDICINE

Azithromycin Reverses Airflow Obstruction in Established Bronchiolitis Obliterans Syndrome

Q1 · MEDICINE

Article

Author: Forrest, Ian A. ; Rutherford, Robert M. ; Dark, John H. ; Yates, Bryan ; Lordan, James L. ; Corris, Paul A. ; Ward, Chris ; Fisher, Andrew J. ; Murphy, Desmond M.

INTRODUCTIONA recent pilot study noted clinical benefit of macrolide therapy in the management of six lung transplant recipients with bronchiolitis obliterans syndrome (BOS), a condition previously regarded as irreversible.OBJECTIVETo examine the effect of low-dose macrolides on lung function in lung allograft recipients with established BOS and to assess whether this benefit is sustained.METHODSWe retrospectively evaluated the effect of azithromycin (250 mg alternate days) on clinical status and lung function in 20 allograft recipients with established BOS, confirmed by decline in FEV(1) or FEF(25-75); consistent high-resolution computed tomography findings; and exclusion of acute rejection, infection, or anastomatic complications. Azithromycin was introduced at mean 82 months after transplantation. BOS staging at initiation of treatment was BOS 3 (10), BOS 2 (2), BOS 1 (6), and BOS0-p (2). All patients were on maintenance immunosuppression comprising cell-cycle inhibitor, oral corticosteroids, and calcineurin inhibitor.RESULTSThere was a significant increase in FEV(1) of median 110 ml (range, -70 to 730 ml) between baseline and 3 months of azithromycin therapy (p = 0.002). This improvement was sustained beyond 3 months in the majority of patients, who had initially benefited from azithromycin (up to 11 months follow up).CONCLUSIONSThis case series confirms the benefit of azithromycin in not only halting, but reversing the declining lung function seen in patients with BOS. This benefit appears to be maintained over time. Low-dose macrolides offer a new and exciting therapeutic strategy for the treatment of progressive BOS, and further clinical and translational mechanistic studies are required.

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Neoplasms	Preclinical	US	Odyssey Therapeutics, Inc.Startup	04 Apr 2023

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