HIGH-DOSE CHEMOTHERAPY AND AUTOLOGOUS BONE-MARROW TRANSPLANTATION FORPATIENTS WITH POOR-PROGNOSIS NONSEMINOMATOUS GERM-CELL TUMORS

Twenty-one patients with poor prognosis nonseminomatous germ cell tumo urs (six with extreme burden disease at presentation in whom partial r emission had been achieved with initial induction therapy, and 15 with recurrent disease after induction therapy) were treated with high-dos e chemotherapy and autologous bone marrow transplantation (BMT). The f irst six received etoposide 3.0 g m-2, ifosfamide 6.0 g m-2 and carbop latin 1.2 g m-2 (Regimen 1), and the subsequent 15 received etoposide 2.4 g m2 (continuous infusion), cyclophosphamide 7.2 g m-2 and carbopl atin 0.8 g m-2 (Regimen 2) followed by infusion of previously stored a utologous marrow. Regimen 1 was associated with considerable renal tox icity and mucositis, whereas Regimen 2 was relatively well tolerated. Two patients died as a consequence of the treatment: one of candidemia and one of interstitial pulmonary fibrosis. Only one of 17 patients w ho were autografted in or approaching marker remission subsequently de veloped disease progression (event-free survival 82%, 95% confidence i nterval [CI] 55% to 94%), whereas all four patients who had progressiv e disease at autografting subsequently developed further disease progr ession and died. Fourteen patients remain well and free of disease 0.5 to 6.5 years (median 3.3) post-BMT (event-free survival 67%, 95% CI 4 3% to 83%). A strategy of prompt reinduction followed by high-dose che motherapy and autologous BMT at the first sign of failure of standard therapy may allow cure to be a realistic expectation.