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 gradually through cooperative therapy studies, so that meanwhile 55 to 65% of the 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 outcome in this patient cohort. Feasibility of this intense megatherapy regimen is crucially dependent on collaboration and multidisciplinary coordination of radiologists, radiotherapists, surgeons and oncologists.


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 still be detected after the third chemotherapy block. During the fifth and sixth chemotherapy block, patients received local irradiation on all infiltrated sites. Persisting immunosuppression after high-dose treatment may facilitate the incidence of relapse. To improve proliferation and cytotoxic activity 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 alive 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 through the use of G-CSF and CD34+ selected stem cells. At the same time, erythrocyte and platelet replacement was shortened. Frequently occurring complications were mucositis and infections. One patient died after developing septicemia and multi-organ failure, another patient developed a myelodysplastic syndrome 4.5 years after megatherapy. However, relapse is still the major cause of death. The influence of IL-2 on event-free survival cannot valued because 21 of 25 patients were treated with adoptive immunotherapy.


CONCLUSIONS
The complex diagnostic and therapeutic strategy renders and 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 standardized treatment strategy is necessary to accumulate a sufficient number of patients for large cooperative studies in this subject.
Laws
H J
HJ
Department of Pediatric Hematology and Oncology, Heinrich Heine University Medical Center Düsseldorf. laws@uni-duesseldorf.de
Burdach
S
S
van Kaick
B
B
Engel
B
B
Dirksen
U
U
Körholz
D
D
Pape
H
H
Kahn
T
T
Merck
H
H
Schmitz
M
M
Heyll
A
A
Dockhorn-Dworniczak
B
B
Jürgens
H
H
Göbel
U
U
D000293:Adolescent; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001859:Bone Neoplasms / Q000188:drug therapy / Q000401:mortality / Q000532:radiotherapy*; D002648:Child; D003131:Combined Modality Therapy; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D008297:Male; D020360:Neoadjuvant Therapy; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy / Q000401:mortality / Q000532:radiotherapy; D009378:Neoplasms, Multiple Primary / Q000188:drug therapy / Q000401:mortality / Q000532:radiotherapy; D010027:Osteotomy; D010348:Patient Care Team; D012512:Sarcoma, Ewing / Q000188:drug therapy / Q000401:mortality / Q000532:radiotherapy*; D015996:Survival Rate; D016896:Treatment Outcome; D014916:Whole-Body Irradiation