Autologous Stem-Cell Transplantation Outcomes for Relapsed Metastatic Germ-Cell Tumors in the Modern Era

Background: High-dose chemotherapy (HDCT) with autologous stem-cell transplantation (aSCT) has been a standard therapy for relapsed metastatic germ-cell tumors (GCTs) over the last 2 decades, but there have been many changes in practice over time with respect to stem-cell source, mobilization, and conditioning regimens. Mobilization is impaired with greater cisplatin exposure.

Patients and methods: Patients with relapsed GCT who received HDCT/aSCT at Dana-Farber Cancer Institute between 1997 and 2017 were identified. Diagnosis, first-line chemotherapy, stem-cell mobilization, HDCT, toxicity, and survival outcomes were annotated and descriptively summarized. Univariable associations of clinicopathologic features and relapse and survival were assessed. Time-to-event analyses were performed by HDCT type and duration.

Results: Thirty-five eligible patients were identified. The most common regimen before HDCT was paclitaxel, ifosfamide, and cisplatin, and it resulted in a high rate of successful initial mobilization (95%). Ten patients (29%) were mobilized with filgrastim and plerixafor (CXCR4 antagonist). All plerixafor-treated patients were mobilized with sufficient cells for 2 transplants. Oxazaphosphorine (cyclophosphamide or ifosfamide)-containing (O-C) HDCT was provided between 1997 and 2008, and subsequent patients were treated with high-dose carboplatin plus etoposide (CE). O-C HDCT was associated with excessive cardiac (33%), severe liver (93%), and renal dysfunction compared to CE. Two O-C-treated patients died of drug-related lung toxicity. Fifty-one percent of the cohort experienced relapse, and 46% died.

Conclusion: Plerixafor has a role in stem-cell mobilization and aSCT for relapsed GCT when cisplatin in bridging before HDCT may be problematic. O-C and CE HDCT regimens have different toxicity patterns that are clinically meaningful.