Clinical impact of germ cell tumor cells in apheresis products of patients receiving high-dose chemotherapy.
OBJECTIVE
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.


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.


CONCLUSIONS
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.
Bokemeyer
C
C
Department of Hematology/Oncology, University of Tuebingen, Tuebingen. carsten.bokemeyer@med.uni-tuebingen.de
Gillis
A J
AJ
Pompe
K
K
Mayer
F
F
Metzner
B
B
Schleucher
N
N
Schleicher
J
J
Pflugrad-Jauch
G
G
Oosterhuis
J W
JW
Kanz
L
L
Looijenga
L H
LH
D000293:Adolescent; D000328:Adult; D014408:Biomarkers, Tumor; D016022:Case-Control Studies; D017931:DNA Primers; D018572:Disease-Free Survival; D005500:Follow-Up Studies; D018237:Germinoma / Q000401:mortality / Q000628:therapy*; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007937:Leukapheresis; D008297:Male; D008875:Middle Aged; D009360:Neoplastic Cells, Circulating; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012680:Sensitivity and Specificity; D015996:Survival Rate
D014408:Biomarkers, Tumor; D017931:DNA Primers