CORRESPONDENCE: LETTER TO THE EDITOR
The BALANCE StudyToo Early to Speculate on Mortality Effects
Thomas Thum, MD, PhD* and
Stefan Anker, MD, PhD
* Department of Molecular and Translational Therapeutic Strategies, Hannover Medical School, Carl-Neuberg-Str. 1, 30625 Hannover, Germany (Email: Thum.Thomas{at}mh-hannover.de).
We read with great interest the paper by Yousef et al. (1) and the accompanying editorial (2) demonstrating and discussing long-term data on cardiac function and mortality in patients treated with autologous bone marrow cell (BMC) transplantation after myocardial infarction.
We do not agree with the editorial's statement that, based on the new data, BMC infusion "can now be considered safe and modestly efficacious" (2), despite the finding that fatal events were more frequent in the control group. The patient cohort studied and the event rate observed were far too small to draw such conclusions. The total number of fatal events was only 8. Also, if the authors had included hospitalizations in the analyses, as is often done in outcome studies, such a combined end point would not have provided conclusive results. Of note, taking the results from Table 1 of their paper (1), there were 9 unplanned hospitalizations in the BMC group and 8 in the intervention group.
In addition, a recent 4-year follow-up study with 86 patients, despite slight improvements in cardiac function, could not identify significant differences in myocardial viability or mortality (3). The BALANCE (Clinical Benefit and Long-Term Outcome After Intracoronary Autologous Bone Marrow Cell Transplantation in Patients With Acute Myocardial Infarction) trial thus may be viewed as a successful proof-of-principle study, but there still is a need for large-scale, placebo-controlled, double-blind clinical end point studies to justify any conclusion with regard to safety or even mortality. Fortunately, such large trials are currently underway at several places worldwide and will clarify those important outstanding issues.
Furthermore, the authors addressed paracrine effects of transplanted autologous cells as the major mechanism explaining the beneficial effects of BMC transplantation. In our view, additional mechanisms should be taken into account. BMC transplantation into an ischemic area results in modulation of the local tissue immune system and altered cytokine production (4). Indeed, BMC transplantation results in local inflammatory changes that activate myofibroblasts, thus reducing infarct size (5). Thus, modulation of pro- and anti-inflammatory intramyocardial cytokine levels by transplanted cells and their crosstalk with the local tissue environment likely affect survival and differentiation of progenitor cells, as well as overall cardiac outcome.
 |
References
|
|---|
1. Yousef M, Schannwell CM, Köstering M, Zeus T, Brehm M, Strauer BE. The BALANCE study: clinical benefit and long-term outcome after intracoronary autologous bone marrow cell transplantation in patients with acute myocardial infarction J Am Coll Cardiol 2009;53:2262-2269.[Abstract/Free Full Text]2. Forrester JS, Makkar RR, Marbán E. Long-term outcome of stem cell therapy for acute myocardial infarction: right results, wrong reasons J Am Coll Cardiol 2009;53:2270-2272.[Free Full Text] 3. Cao F, Sun D, Li C, et al. Long-term myocardial functional improvement after autologous bone marrow mononuclear cells transplantation in patients with ST-segment elevation myocardial infarction: 4 years follow-up Eur Heart J 2009;30:1986-1994.[Abstract/Free Full Text] 4. Thum T, Bauersachs J, Poole-Wilson PA, Volk HD, Anker SD. The dying stem cell hypothesis: immune modulation as a novel mechanism for progenitor cell therapy in cardiac muscle J Am Coll Cardiol 2005;46:1799-1802.[Abstract/Free Full Text] 5. Sun J, Li SH, Liu SM, et al. Improvement in cardiac function after bone marrow cell therapy is associated with an increase in myocardial inflammation Am J Physiol Heart Circ Physiol 2009;296:43-50.[CrossRef]
Related Articles
-
Reply
- Bodo-Eckehard Strauer, Michael Brehm, Christiana Mira Schannwell, and Muhammad Yousef
J. Am. Coll. Cardiol. 2010 55: 264.
[Full Text]
[PDF]
-
The BALANCE Study: Clinical Benefit and Long-Term Outcome After Intracoronary Autologous Bone Marrow Cell Transplantation in Patients With Acute Myocardial Infarction
- Muhammad Yousef, Christiana Mira Schannwell, Mathias Köstering, Tobias Zeus, Michael Brehm, and Bodo Eckehard Strauer
J. Am. Coll. Cardiol. 2009 53: 2262-2269.
[Abstract]
[Full Text]
[PDF]
|
Top
References