Clinical impact of germ cell tumor cells in apheresis products of patientsreceiving high-dose chemotherapy

Purpose: High-dose chemotherapy (HD-Ctx) followed by autologous peripheral- blood stem-cell (PBSC) transplantation is currently investigated in patient s with poor prognosis or relapsed metastatic germ cell tumor (GCTs). This s tudy analyzed the presence and the clinical importance of contaminating tum or cells in PBSC preparations used to support HD-Ctx in GCT patients. Patients and Methods: Seven targets for reverse transcription polymerase ch ain reaction (RT-PCR)-based detection of GCT cells were able to detect semi nomatous and different histologic variants of nonseminomatous tumor cells. PBSC preparations from 57 patients were investigated for the presence of co ntaminating tumor cells using this set of targets, including beta human cho rionic gonadotropin (beta -hCG), fibronectin (EDB variant), epidermal growt h 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 allog enic 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 asse ssable. Combining all RT-PCR results, 29 PBSC preparations (58%) were posit ive for tumor-specific amplification products (HERV-K 0, fibronectin 4, XIS T 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%) o f 21 patients with negative PBSC preparations have suffered relapse or prog ression (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 posit ivity 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 tum or cells, retransplantation of the PBSC products did not effect long-term o utcome. Factors such as responsiveness to chemotherapy and tumor mass seem to overcome the importance of potentially re-infused tumor cells, J Clin On col 19:3029-3036. (C) 2001 by American Society of Clinical Oncology.