Letters to the Editor: Persistent DNA
Dear Editor,
As noted by the authors of the article Serena TE, Bialas P. Persistence of bilayered living-cell therapy donor DNA 10 months after application: a case report. (Ostomy Wound Manage. 2009;55[10]18–22), 10 months is considerably longer persistence than previously reported in multiple studies. In six published studies involving 52 patients,1-6 no Apligraf (Organogenesis, Canton, MA) cells were found (by RT-PCR) at 6 weeks following application and only one (a single study in patients treated for epidermolysis bullosa, the data of which the author concluded were not convincing) detected allogeneic material beyond 6 weeks.2
No preclinical or clinical evidence exists that the bilayered living-cell product provokes a host-immune reaction but there is no evidence of vascularization or recognition of long-term tissue integration.3,5,7 A silent immune recognition to the bilayered living-cell product’s allogeneic fibroblasts and keratinocytes may play a part in these findings.4 Given the inconsistency of the persistence findings in this case with the weight of clinical and scientific evidence to date, the most probable explanation for the findings in this study is the authors’ observation that the patient was likely immunocompromised at the time of application of the cell therapy. Ecthyma gangrenosum is a relatively unusual condition seen primarily in patients with underlying immunodeficiency or malignancy.8-10 It seems likely that this case represents a rare phenomenon related to the patient, not the allogeneic cell therapy. It would be interesting to know whether any testing has been done in follow-up of this possibility. There is currently no evidence that the bilayered living-cell product engrafts in immunocompetent patients; rather, it improves the rate and quality of healing by secondary intention.11-13
David Hurley, MD and Damien Bates, MD, PhD FRACS (Plast)
Reply
Drs. Hurley and Bates from Organogenesis are correct in pointing out that the preponderance of evidence in the literature suggests that the bilayered cell therapy product (Apligraf®) does not persist beyond a few weeks. Moreover, in more than a decade of personal experience with the product, I have seen only a minimum number of cases in which I suspected that the product may have persisted in some fashion. However, the patient in the current report was remarkable from the start: The unusual appearance of the wound demanded investigation.
We considered, as the doctors suggest, that the bilayered living-cell product may have persisted because the patient was immunosuppressed at the time of application. This is possible, but not plausible. The bilayered cell therapy was applied 3 weeks after presentation to our hospital. The patient was well on the road to recovery from his sepsis at that point; he did not suffer from an undiagnosed malignancy. Quite the contrary: after surviving this life-threatening illness, he returned home to rural Pennsylvania and lived a quiet normal life, taking only cardiac medications. He was clearly not immunosuppressed when he walked back into the wound clinic 10 months later (when we performed the biopsy looking for persistence). In the end, he went on to live for another several years before succumbing to an unrelated disease.
I do not believe that this case will change the way in which wound care specialists ply their art. The bilayered living-cell product does not promote healing in chronic wounds because it exhibits “graft take,” becoming vascularized like an autograft. This patient’s unique response to transplanted neonatal foreskin cells represents a rare and fascinating phenomenon: the creation of chimeric skin in a non-immunosuppressed adult.
Isn’t biology wonderful?
Thomas E. Serena, MD, FACS
This article was not subject to the Ostomy Wound Management peer-review process.
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