Allogeneic and autologous stem-cell transplantation in advanced Ewing tumors. An update after long-term follow-up from two centers of the European Intergroup study EICESS. Stem-Cell Transplant Programs at Düsseldorf University Medical Center, Germany and St. Anna Kinderspital, Vienna, Austria.
BACKGROUND
An update of results from the High Risk Protocol of the Meta-EICESS Study, conducted at the Pediatric Stem-Cell Transplant Centers of Düsseldorf and Vienna. In order to evaluate a possible therapeutic benefit after allogeneic SCT in patients with advanced Ewing tumors (AET), we compared outcome after autologous and allogeneic stem-cell transplantation (SCT).


METHODS
We analyzed 36 patients treated with the myeloablative Hyper-ME protocol (hyperfractionated total body irradiation, melphalan, etoposide +/- carboplatin) between November 1986 and December 1994. Minimal follow-up for all patients was five years. All patients underwent remission induction chemotherapy and local treatment before myeloablative therapy. Seventeen of thirty-six patients had multifocal primary Ewing's tumor, eighteen of thirty-six had early, multiple or multifocal relapse, one of thirty-six patients had unifocal late relapse. Twenty-six of thirty-six were treated with autologous and ten of thirty-six with allogeneic hematopoietic stem cells. We analyzed the following risk factors, that could possibly influence the event-free survival (EFS): number of involved bones, degree of remission at time of SCT, type of graft, indication for SCT, bone marrow infiltration, bone with concomitant lung disease, age at time of diagnosis, pelvic involvement, involved compartment radiation, histopathological diagnosis.


RESULTS
EFS for the 36 patients was 0.24 (0.21) +/- 0.07. Eighteen of thirty-six patients suffered relapse or died of disease, nine of thirty-six died of treatment related toxicity (DOC). Nine of thirty-six patients are alive in CR. Age > or = 17 years at initial diagnosis (P < 0.005) significantly deteriorated outcome. According to the type of graft, EFS was 0.25 +/- 0.08 after autologous and 0.20 +/- 0.13 after allogeneic SCT. Incidence of DOC was more than twice as high after allogeneic (40%) compared to autologous (19%) SCT, even though the difference did not reach significance (P = 0.08, Fisher's exact test).


CONCLUSIONS
Because of the rather short observation period. secondary malignant neoplasms (SMN) may complicate the future clinical course of some of our patients who are currently viewed as event-free survivors. EFS in AET is not improved by allogeneic SCT due to a higher complication rate. The patient group was to small to analyze for a possible graft-versus-tumor effect.
Burdach
S
S
Division of Pediatric Hematology/Oncology, Children' s Hospital Medical Center, Martin Luther University Halle-Wittenberg, Halle, Germany. stefan.burdach@medizin.uni-halle.de
van Kaick
B
B
Laws
H J
HJ
Ahrens
S
S
Haase
R
R
Körholz
D
D
Pape
H
H
Dunst
J
J
Kahn
T
T
Willers
R
R
Engel
B
B
Dirksen
U
U
Kramm
C
C
Nürnberger
W
W
Heyll
A
A
Ladenstein
R
R
Gadner
H
H
Jürgens
H
H
Go el
U
U
D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001859:Bone Neoplasms / Q000188:drug therapy / Q000401:mortality / Q000601:surgery / Q000628:therapy*; D019090:Case Management; D002423:Cause of Death; D002648:Child; D003131:Combined Modality Therapy; D018572:Disease-Free Survival; D019583:Dose Fractionation, Radiation; D005260:Female; D005500:Follow-Up Studies; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007155:Immunologic Factors / Q000627:therapeutic use; D007376:Interleukin-2 / Q000627:therapeutic use; D008297:Male; D009190:Myelodysplastic Syndromes / Q000209:etiology; D009362:Neoplasm Metastasis; D016609:Neoplasms, Second Primary / Q000453:epidemiology; D011379:Prognosis; D018714:Radiotherapy, Adjuvant; D012074:Remission Induction; D012307:Risk Factors; D012512:Sarcoma, Ewing / Q000188:drug therapy / Q000401:mortality / Q000601:surgery / Q000628:therapy*; D016019:Survival Analysis; D019172:Transplantation Conditioning; D014182:Transplantation, Autologous; D014184:Transplantation, Homologous; D016896:Treatment Outcome
D007155:Immunologic Factors; D007376:Interleukin-2