Secondary leukemias in refractory germ cell tumor patients undergoing autologous stem-cell transplantation using high-dose etoposide.

PURPOSE: To quantify the risk of secondary leukemias in relapsed testicular cancer patients undergoing autologous stem-cell transplantation with high-dose etoposide.

PATIENTS AND METHODS: Single institution, retrospective study of germ cell tumor patients who underwent autologous transplantation using high-dose etoposide from 1987 to 2001.

RESULTS: One hundred thirteen patients received high-dose etoposide and carboplatin followed by autologous stem-cell transplantations for germ cell tumors. Follow-up ranged from 12 to 166 months (median, 51 months). Three patients (2.6%; 95% CI, 0.55% to 7.50%) subsequently developed leukemia at an average of 16 months post-autologous transplantation (range, 11 to 21 months). All three had received tandem transplantations and had been heavily pretreated, including at least one prior cycle of etoposide. Following autologous transplantation, all three patients exhibited refractory cytopenias before developing overt leukemia. All leukemias were of myeloid lineage. One patient developed an M2 with a t(8,21) chromosomal translocation; another, an M5 with a t(11,19); and one patient exhibited an unclassified leukemia with cytogenetic abnormalities resulting in monosomy for 7p and partial monosomy of 7q. Treatment of the leukemias involved allogeneic bone marrow transplantation.

CONCLUSION: High-dose chemotherapy using high-dose etoposide as therapy for relapsed germ cell tumors was associated with a 2.6% risk of developing a secondary myeloid leukemia. This figure was not significantly different from the expected rate of secondary leukemias when patients receive additional cycles of standard-dose etoposide as salvage chemotherapy for germ cell tumors. Other factors, including the use of platinum agents, may also have a role in leukemogenesis in this patient population.