Secondary malignancies after high-dose chemotherapy in germ cell tumor patients: a 34-year retrospective study of the European Society for Blood and Marrow Transplantation (EBMT)

We aimed to assess the incidence and risk factors of secondary malignancy (SM) in the young adult patients who received high-dose chemotherapy (HDCT) for germ cell tumors (GCT). The EBMT database was interrogated. Criteria for patient selection included adult male GCT and HDCT administered in any line of therapy. Cumulative incidence methods were used to estimate the time-to-SM diagnosis. Univariable Fine and Gray proportional hazard regression evaluated risk factors of SM occurrence. From 1981 to 2015, 9153 autografts were identified. Among 5295 patients, 59 cases of SM, developed after a median follow-up of 3.8 years, were registered. Of these patients, 23 (39%) developed hematologic SM, 34 (57.6%) solid SM (two patients had uncoded SM). Twenty-year cumulative incidence of solid versus hematologic SM was 4.17% (95% CI: 1.78-6.57) versus 1.37% (95% CI: 0.47-2.27). Median overall survival after SM was significantly shorter for patients who developed hematologic SM versus solid SM (8.6 versus 34.4 months, p = 0.003). Age older than 40 years at the time of HDCT was significantly associated with hematologic, but not solid, SM development (p = 0.004 versus p = 0.234). SM occurrence post-HDCT showed different patterns of incidence and mortality in GCT. These data may be important to optimize patient selection, counseling and follow-up after HDCT.