Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Higher cancer rates found in liver transplant patients receiving cyclosporine for immunosuppression

25.06.2010
C2 monitoring and age are key factors

Researchers at Erasmus MC University Medical Centre in The Netherlands found that cyclosporine treatment is a significant risk factor for the development of de novo cancer in liver transplant patients. Full details appear in the July issue of Liver Transplantation, a journal published by Wiley-Blackwell on behalf of the American Association for the Study of Liver Diseases (AASLD).

The 1-year survival rate after liver transplantation has dramatically increased in the past three decades to more than 80%. In contrast, there has been little improvement in long-term outcomes. Malignancy is one of the major leading causes of late death after liver transplant and is reported to be directly related to the intensity and the cumulative dose of immunosuppression.

Calcineurin inhibitors (CNI) such as cyclosporine (CsA) or tacrolimus (TAC) are the cornerstone of immunosuppressive treatment after transplantation. Several studies have yielded conflicting results about the incidence of de novo cancer between CsA- based and TAC-based regimens. Elucidating the role of different CNI regimens in the occurrence of de novo cancer after liver transplant was the goal of this study.

The Dutch team performed retrospective analyses in 385 liver transplant patients who underwent surgery between 1986 and 2007. Analyzed data included age of recipient at time of transplantation, gender of recipient, primary liver transplant indication, type of primary immunosuppressive therapy, de novo malignancy post transplantation, interval from liver transplant to diagnosis of malignancy, interval from liver transplant or diagnosis of cancer to death and interval from liver transplant to diagnosis of the first acute rejection. All patients were followed until December 2008. The primary endpoint was de novo malignancy, which was defined as the development of cancer other than recurrent primary liver cancer. Of the 385 study participants, 50 (13.0%) patients developed at least one de novo cancer.

The researchers observed that CsA in comparison to TAC treatment is the most important risk factor for de novo malignancy after liver transplant. This higher cancer risk was not, however, found in all CsA treated patients, but CsA specifically enhanced development of de novo cancer in patients transplanted in more recent years (2005-2007), and in younger patients (less than 50 years of age). In addition, CsA treatment particularly resulted in more aggressive types of cancer compared to TAC, with a 1-year survival rate less than 30%.

The reason for the increased cancer rates among CsA recipients is believed to be the fact that from January 2005, CsA dosing based on the conventional C0 level monitoring was replaced by dosing based on C2 level monitoring in all liver transplant patients. As this was the only major change in the CsA treatment in the recent study period, the team concludes that the C2 monitoring strategy was the reason for the increased early de novo cancer risk.

"Strikingly, CsA treated patients transplanted from 2005 on showed a 9.9-fold higher de novo cancer risk in the early phase after liver transplant compared to patients treated with TAC. These data indicate that only the specific CsA treatment used in recent years was associated with a higher risk for early development of de novo cancer," said research team leader Herold Metselaar, M.D., Ph.D. "We also observed that, compared with TAC treated patients, CsA treated patients had a 2.5-times higher risk to develop more aggressive cancer types that do not belong to the non-melanoma skin cancer and post-transplant lymphoproliferative disorder (PTLD) categories, indicating that CsA is not only associated with a higher early de novo cancer risk, but also with cancer types having a worse prognosis."

In this month's editorial, Julie Thompson, M.D., suggests that further study is required, stating, "Metselaar and colleagues draw much-needed attention to concerns regarding overall immunosuppressant exposure and its relationship to long-term outcomes after liver transplantation. These data serve as a call to reassess the aggressiveness of current immunosuppressive regimens as a means of reducing risk from de novo malignancy."

Article: "Increased Incidence of Early de novo Cancer in Liver Graft Recipients Treated with Cyclosporine: An Association with C2 Monitoring and Recipient Age." Angela S.W. Tjon, Jerome Sint Nicolaas, Jaap Kwekkeboom, Robert A. de Man, Geert Kazemier, Hugo W. Tilanus, Bettina E. Hansen, Luc J.W. van der Laan, Thanyalak Tha-In, Herold J. Metselaar. Liver Transplantation; Published Online: March 8, 2010 (DOI: 10.1002/lt.22064 ); Print Issue Date: July 2010. http://www3.interscience.wiley.com/journal/123313851/abstract

Editorial: "Immunosuppression, Cancer, and the Long-Term Outcomes after Liver Transplantation: Can We Do Better?" James M. Abraham, Julie A. Thompson. Liver Transplantation; Published Online: May 31, 2010 (DOI: 10.1002.lt.22114); Print Issue Date: July 2010.

This study is published in Liver Transplantation. Media wishing to receive a PDF of this article may contact healthnews@wiley.com

Liver Transplantation is published on behalf of The American Association for the Study of Liver Diseases and the International Liver Transplantation Society. Since the first application of Liver Transplantation in a clinical situation was reported more than twenty years ago, there has been a great deal of growth in this field and more is anticipated. As an official publication of the AASLD and the ILTS, Liver Transplantation delivers current, peer-reviewed articles on surgical techniques, clinical investigations and drug research — the information necessary to keep abreast of this evolving specialty. For more information, please visit http://www3.interscience.wiley.com/journal/106570021/home.

Wiley-Blackwell is the international scientific, technical, medical, and scholarly publishing business of John Wiley & Sons, Inc., with strengths in every major academic and professional field and partnerships with many of the world's leading societies. Wiley-Blackwell publishes nearly 1,500 peer-reviewed journals and 1,500+ new books annually in print and online, as well as databases, major reference works and laboratory protocols. For more information, please visit www.wileyblackwell.com or www.interscience.wiley.com

Dawn Peters | EurekAlert!
Further information:
http://www.wiley.com

Further reports about: AASLD Association CNI Cancer DOI Liver Transplant Metselaar TAC Transplantation risk factor

More articles from Studies and Analyses:

nachricht Study relating to materials testing Detecting damages in non-magnetic steel through magnetism
23.07.2018 | Technische Universität Kaiserslautern

nachricht Innovative genetic tests for children with developmental disorders and epilepsy
11.07.2018 | Christian-Albrechts-Universität zu Kiel

All articles from Studies and Analyses >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Unraveling the nature of 'whistlers' from space in the lab

A new study sheds light on how ultralow frequency radio waves and plasmas interact

Scientists at the University of California, Los Angeles present new research on a curious cosmic phenomenon known as "whistlers" -- very low frequency packets...

Im Focus: New interactive machine learning tool makes car designs more aerodynamic

Scientists develop first tool to use machine learning methods to compute flow around interactively designable 3D objects. Tool will be presented at this year’s prestigious SIGGRAPH conference.

When engineers or designers want to test the aerodynamic properties of the newly designed shape of a car, airplane, or other object, they would normally model...

Im Focus: Robots as 'pump attendants': TU Graz develops robot-controlled rapid charging system for e-vehicles

Researchers from TU Graz and their industry partners have unveiled a world first: the prototype of a robot-controlled, high-speed combined charging system (CCS) for electric vehicles that enables series charging of cars in various parking positions.

Global demand for electric vehicles is forecast to rise sharply: by 2025, the number of new vehicle registrations is expected to reach 25 million per year....

Im Focus: The “TRiC” to folding actin

Proteins must be folded correctly to fulfill their molecular functions in cells. Molecular assistants called chaperones help proteins exploit their inbuilt folding potential and reach the correct three-dimensional structure. Researchers at the Max Planck Institute of Biochemistry (MPIB) have demonstrated that actin, the most abundant protein in higher developed cells, does not have the inbuilt potential to fold and instead requires special assistance to fold into its active state. The chaperone TRiC uses a previously undescribed mechanism to perform actin folding. The study was recently published in the journal Cell.

Actin is the most abundant protein in highly developed cells and has diverse functions in processes like cell stabilization, cell division and muscle...

Im Focus: Lining up surprising behaviors of superconductor with one of the world's strongest magnets

Scientists have discovered that the electrical resistance of a copper-oxide compound depends on the magnetic field in a very unusual way -- a finding that could help direct the search for materials that can perfectly conduct electricity at room temperatur

What happens when really powerful magnets--capable of producing magnetic fields nearly two million times stronger than Earth's--are applied to materials that...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Within reach of the Universe

08.08.2018 | Event News

A journey through the history of microscopy – new exhibition opens at the MDC

27.07.2018 | Event News

2018 Work Research Conference

25.07.2018 | Event News

 
Latest News

Unraveling the nature of 'whistlers' from space in the lab

15.08.2018 | Physics and Astronomy

Diving robots find Antarctic winter seas exhale surprising amounts of carbon dioxide

15.08.2018 | Earth Sciences

Early opaque universe linked to galaxy scarcity

15.08.2018 | Physics and Astronomy

VideoLinks
Science & Research
Overview of more VideoLinks >>>