Multimodality diagnostics and megatherapy in poor prognosis Ewing's tumor patients - A single-center report

Background: The prognosis of Ewing's tumor patients has been improved gradu ally through cooperative therapy studies, so that meanwhile 55 to 65% of th e patients survive relapse-free in the long term. Patients with multifocal primary, early or multiply-relapsed Ewing's tumors have a dismal prognosis. Megatherapy with subsequent stem cell transplantation seems to improve out come in this patient cohort. Feasibility of this intense megatherapy regime n is crucially dependent an collaboration and multidisciplinary coordinatio n of radiologists, radiotherapists, surgeons and oncologists. Patients and Methods: Since 1988, 25 patients were treated with megatherapy consisting of melphalan, etoposide and total-body irradiation followed by stem cell transplantation. All patients received 6 courses of an induction therapy. Before the fourth therapy block, tumors that were bulky at initial diagnosis (>200 ml) were excised, as well as lung metastases which could s till be detected after the third chemotherapy block. During the fifth and s ixth chemotherapy block, patients received local irradiation on all infiltr ated sites. Persisting immunosuppression after high-dose treatment may faci litate the incidence of relapse. To improve proliferation and cytotoxic act ivity of early regenerating Nk-cells, adoptive immunotherapy with systemic IL-2 therapy after megatherapy is part of the treatment protocol. Results: Of 25 patients treated with megatherapy, 10 patients are still ali ve with a follow-up time of 6 months to 9 years after megatherapy. The time up to engraftment was decreased from 15 +/- 6 days down to 9 +/- 2 days th rough the use of G-CSF and CD34+ selected stem cells. At the same time, ery throcyte and platelet replacement was shortened. Frequently occurring compl ications were mucositis and infections. One patient died after developing s epticemia and multiorgan failure, another patient developed a myelodysplast ic syndrome 4.5 years after megatherapy. However, relapse is still the majo r cause of death. The influence of IL-2 on event-free survival cannot value d because 21 of 25 patients were treated with adoptive immunotherapy. Conclusion: The complex diagnostic and therapeutic strategy renders an EFS of 34% For a patient group with otherwise dismal prognosis. To clarify the efficiency of megatherapy in patients with advanced Ewing's tumors, a stand ardized treatment strategy is necessary to accumulate a sufficient number o f patients for large cooperative studies in this subject.