Busulfan, melphalan, and thiotepa with or without total marrow irradiationwith hematopoietic stem cell rescue for poor-risk Ewing-sarcoma-family tumors

Background. Survival following metastatic or recurrent Ewing sarcoma family tumors (ESFT) remains <25%. Myeloablative therapy with hematopoietic stem cell transplantation (HSCT) may improve survival for poor-risk ESFT. We des cribe the toxicity and efficacy of a myeloablative chemotherapy regimen, fo llowed by a second myeloablative radiotherapy regimen as consolidation trea tment for poor-risk ESFT. Procedure. Sixteen patients with poor-risk ESFT w ere treated with myeloablative therapy followed by HSCT. All patients recei ved busulfan, melphalan, and thiotepa (BuMelTT) as chemotherapy conditionin g. Nine patients received total marrow irradiation (TMI) as a second myeloa blative therapy, also followed by HSCT. Seven patients were excluded from T MI because of inadequate peripheral blood stem cell harvest, extensive prio r radiation therapy, early disease progression, orpatient refusal. The dise ase status prior to my eloablative therapy was first complete response (CR1 ) in three patients, CR2 in nine, second partial response (PR2) in one, CR3 in one, and progressive disease (PD) in two. Results. One patient died of regimen-related toxicity, one from late pulmonary toxicity, and one followi ng allogeneic transplantation for myelodysplasia. Eight developed recurrent disease (median time to progression 6.8 months). Six survive without relap se from 27 to (66 months following BuMelTT (median follow-up 42 mont)ls), a ll of whom received both BuMelTT and TMI patients (3-year event-free surviv al 36%). Conclusions. Dual myeloablative therapy with BuMelTT and TMI was a feasible and promising treatment approach for patients with, poor-risk ESF T. Inability to collect sufficient PBSC and extensive previous radiation th erapy limit the ability to deliver TMI as a second HSCT conditioning regime n. (C) 2000 Wiley-Liss, Inc.