Intensive combined modality therapy including low-dose TBI in high-risk ewing's sarcoma patients

Abstract

Twenty-four higb-risk Ewing's sarcoma patients were treated on an intensive combined modality protocol including low-dose fractionated total body irradiation (TBI) and autologous bone marrow infusion (ABMI). Twenty patients (83%) achieved a complete clinical response to the primary and/or metastatic sites following induction therapy. The median disease-free interval was 18 months, and nine patients remain disease-free with a follow-up of 22 to 72 months. Local failure as a manifestation of initial relapse occurred in only three patients (15%), each having synchronous distant failure. Eight patients failed initially with only distant metastases, usually within 1–2 years following a complete clinical response. Two patients with a single metastasis were again rendered disease-free and remain free from second relapse with 18 and 30 months of follow-up. No other relapsed patient was able to be rendered disease-free, and most died of progressive disease within 6 to 12 months of relapse. Two patterns of granulocyte recovery following consolidative therapy (including TBI) and ABMI were recognized. Seventeen patients reached a total granulocyte count of >500 cells/mm 3 within 4 weeks of ABMI (early granulocyte recovery), while 7 patients required >4 weeks from ABMI (late granulocyte recovery). The time to platelet recovery (>50,000/mm 3) was different for the groups with early and late granulocyte recovery (25 days vs. 54 days, p > .001). Six of seven patients with late granulocyte recovery received local high-dose irradiation to > 1 2 pelvis prior to bone marrow storage. Patients with) late recovery did not tolerate maintenance chemotherapy. However, there was no difference in disease-free and overall survival, when comparing the groups with early and late granulocyte recovery. We conclude that these high-risk Ewing's sarcoma patients remain a poor-prognosis group in spite of intensive combined modality therapy including low-dose TBI. The control of microscopic systemic disease remains the major challenge to improving the cure rate. A new combined modality protocol with high-dose `therapeutic' TBI (800 rad/2 fractions) is being used and the protocol design is outlined.