ABSTRACT
PURPOSE: High-dose chemotherapy (HD-Ctx) followed by autologous peripheral-blood stem-cell (PBSC) transplantation is currently investigated in patients with poor prognosis or relapsed metastatic germ cell tumor (GCTs). This study analyzed the presence and the clinical importance of contaminating tumor cells in PBSC preparations used to support HD-Ctx in GCT patients. PATIENTS AND METHODS: Seven targets for reverse transcription polymerase chain reaction (RT-PCR)-based detection of GCT cells were able to detect seminomatous and different histologic variants of nonseminomatous tumor cells. PBSC preparations from 57 patients were investigated for the presence of contaminating tumor cells using this set of targets, including beta human chorionic gonadotropin (beta-hCG), fibronectin (EDB variant), epidermal growth factor receptor (EGFR), CD44 (v8 to 10 variant), germ cell and placental alkaline phosphatase (AP), human endogenous retrovirus type K (ENV and GAG), and XIST. Samples of PBSC preparations from four healthy donors for allogenic transplantations as well as blood specimens from 10 healthy volunteers served as negative controls. RESULTS: Fifty patients (43 first-line and seven second-line Ctx) were assessable. Combining all RT-PCR results, 29 PBSC preparations (58%) were positive for tumor-specific amplification products (HERV-K 0, fibronectin 4, XIST 14, beta-hCG 19, AP 19, CD44 24, EGFR 26). Ten (35%) of 29 patients who underwent transplantation with positive PBSC preparations and seven (33%) of 21 patients with negative PBSC preparations have suffered relapse or progression (not significant [ns]). With a median follow-up of 22 months (2 to 66) post-HD-Ctx projected 3-year survival rates are 68% (RT-PCR+) and 58% (RT-PCR-) (ns). None of the 10 control peripheral-blood samples showed positivity for any of the targets studied. CONCLUSION: GCT cells can be detected in more than 50% of PBSC preparations using a RT-PCR approach with multiple targets. Despite the presence of tumor cells, retransplantation of the PBSC products did not effect long-term outcome. Factors such as responsiveness to chemotherapy and tumor mass seem to overcome the importance of potentially re-infused tumor cells.
Subject(s)
Germinoma/therapy , Hematopoietic Stem Cell Transplantation , Leukapheresis , Neoplastic Cells, Circulating , Reverse Transcriptase Polymerase Chain Reaction , Adolescent , Adult , Biomarkers, Tumor , Case-Control Studies , DNA Primers , Disease-Free Survival , Follow-Up Studies , Germinoma/mortality , Humans , Male , Middle Aged , Sensitivity and Specificity , Survival RateABSTRACT
In this study we report on the atherectomy technique, acute and long-term data, and histological findings of excised specimens from patients with peripheral vascular disease treated with the Simpson atherectomy catheter. Forty patients with a total of 72 lesions of the iliac (n = 5), superficial femoral (n = 62), and popliteal (n = 5) arteries could be treated; five patients had rest pain and two had gangrene. The primary success rate (of all lesions, including total occlusions and longer stenoses) was over 90%. The percent of stenosis decreased from 87.2 +/- 19.9% to 16.6 +/- 15.5%; the claudication distance improved from 80.5 +/- 65.7 m to 152.8 +/- 80.3 m; the Doppler index (leg/arm) increased from 0.57 +/- 0.17 to 0.81 +/- 0.16. At 6 months the mean walking distance and Doppler index remained stable from post-atherectomy; the mean percent of stenosis had increased to 35.7 +/- 30.9%. The angiographic restenosis rate (defined as stenosis greater than 70%) was 21% with a clear difference found depending on the primary morphology of the lesion: in eccentrics 5%, concentrics 27%, and total occlusions 42%, thereby allowing categorization of the suitability of a primary lesion for atherectomy. Histologically, restenoses showed more cellular proliferation and organized thrombus as compared to their primary stenoses; further investigations (cell culture, immunohistochemistry, and electron microscopy) are underway.(ABSTRACT TRUNCATED AT 250 WORDS)
