Treatment of metastatic head and neck cancer with mesenchymal stem cells combined with prodrug gene therapy
Summary. This is a clinical observation of a patient treated for metastatic head and neck cancer with mesenchymal stem cells mediated prodrug gene therapy. The cells were applied intravenously. We did not observe any therapeutic effect. However, a temporal bicytopenia was observed.
Submitted: September 24, 2015.
*Correspondence: E-mail: firstname.lastname@example.org
Abbreviation used: TSC – therapeutic stem cells.
A 41 years old male patient with squamous carcinoma of the tongue (T2N0M0) refused any adjuvant chemotherapy after the surgery. He developed lung metastases 9 months after the second surgery for local relapse. After an approval of the Ministry of Health of the Slovak Republic, on day −2 he was admitted to the hospital. Infusion of Ancotil (2.5 g flucytosine/250 ml solution) started on day −1 bid 24 hours before the administration of therapeutic stem cells (TSC), and continued for 7 days. On day 0 the patient received 60×106 allogenic TSC intravenously. The therapeutic adipose tissue-derived mesenchymal stem cells were prepared as described previously . There were no adverse effects during and 6 h after the administration. 18 hours after the intravenous administration of the TSC, the patient developed fever (39.0 °C) with no signs of circulation instability. The fever resolved after antipyretics. There were no signs of any microbial infection. The following days the patient remained afebrile. Due to a sudden drop of white blood cells he received an oral antibacterial and antimycotic prophylaxis. On the day +6 he was discharged from the hospital with almost normalized blood counts. On day +18 during the outpatient control he was doing well. His blood counts (except mild anemia) were normal (Table). The CT scan performed on day +6 showed no difference in the size or density of his pulmonary metastases compared to the CT scan on day −1. On the day +40 there were signs of a progression of the metastases on the CT scan.
Table. Blood counts of the patient during and after the therapy
The treatment with TSC of this patient highlighted two points: 1) There was no sign of any therapeutic effect after intravenous (not local, i.e. intratumoral) administration of the TSC. 6 days after the administration the metastatic process did not show any signs of regression. Moreover, after 40 days after the treatment there was a progression of the metastases. 2) After the intravenous administration the TSC are probably “homing” in the bone marrow despite the adipose tissue origin. Even a rather low cell count (60•106) was able to cause grade 2 (3) thrombopenia (neutropenia). It should be noted that this patient did not receive any systemic chemotherapy in the past. The observed bicytopenia with a nadir occurred 48 h after the administration of TSC (with concomitant prodrug administration). Therefore it should be carefully considered when a medical team decides to use the intravenous route.
We are indebted prof. C. Altaner and his team from the Center for Cell Therapy and Regenerative Medicine for preparing the TSC.
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