Human Leukocyte Antigen Distribution in German Caucasians with Advanced Ewing’s Sarcoma

Abstract

Background:

Risk stratification criteria for patients with Ewing’s sarcoma family of tumors (ESFT) are still limited. We hypothesized divergent human leukocyte antigen (HLA) patterns in ESFT patients and compared HLA-A, -B and -DR phenotype frequencies of patients with advanced ESFT with those of healthy controls.

Patients:

HLA types of all German Caucasian patients with advanced ESFT and available HLA-A, -B and -DR data registered in the European Group for Blood and Marrow Transplantation, Paediatric Registry for Stem Cell Transplantation and the MetaEICESS data bases (study group, n=30) were retrospectively compared with HLA types of healthy German stem cell donors (control group, n=8 862 for single HLA frequencies and n=8 839 for allele combinations). Study group patients had been immuno-typed due to eligibility for allogeneic stem cell transplantation for high risk of treatment failure, and thus constituted a selected subgroup of ESFT patients.

Results:

After Bonferroni correction for multiple testing (PC), phenotype frequencies of HLA-A24 remained significantly higher in the study group compared to controls (PC<0.05). Furthermore, several HLA combinations were significantly more frequent in the study group compared to controls (all PC<0.05).

Conclusion:

We report an increased incidence of circumscribed HLA patterns in German Caucasians with advanced ESFT. The possible clinical significance of this observation has to be re-assessed in prospective trials comprising larger ESFT patient numbers of all risk groups.

Zusammenfassung

Hintergrund:

Die Kriterien zur Risikostratifizierung von Patienten mit Ewing-Sarkomen (ESFT) sind immer noch limitiert. Wir postulierten, dass bei Patienten mit ESFT unterschiedliche humane Leukozytenantigen-(HLA)-Verteilungsmuster im Vergleich zu Gesunden vorliegen, und verglichen deshalb HLA-A, -B und -DR-Merkmalsträgerhäufigkeiten.

Patienten:

Die HLA-Typen aller deutsch-kaukasischen Patienten mit fortgeschrittenem ESFT und verfügbaren HLA-A, -B und -DR-Daten, die in den European Group for Blood and Marrow Transplantation, Pädiatrisches Register für Stammzell-Transplantationen und/oder MetaEICESS- Datenbanken registriert waren (Studiengruppe, n=30), wurden retrospektiv mit den HLA-Typen gesunder deutscher Stammzellspender (Kontrollgruppe, n=8 862 bei einzelnen HLA-Frequenzen und n=8 839 bei HLA-Kombinationen) verglichen. Studienpatienten wurden bei Eignung für eine allogene Stammzelltransplantation aufgrund ihres hohen Rückfallrisikos HLA-typisiert. Die Studiengruppe stellt damit eine selektierte Subgruppe aller ESFT-Patienten dar.

Ergebnisse:

Nach Bonferroni-Korrektur für multiples Testen (PC), war ein statistischer Zusammenhang für ein vermehrtes Auftreten von HLA-A24 in der Studiengruppe im Vergleich zur Kontrollgruppe zu beobachten (PC<0,05). Darüber hinaus traten verschiedene HLA-Kombinationen signifikant häufiger in der Studiengruppe im Vergleich zur Kontrollgruppe auf (alle PC<0,05).

Schlussfolgerung:

Wir berichten über ein vermehrtes Vorkommen von umschriebenen HLA-Konstellationen bei deutschen Kaukasiern mit fortgeschrittenem ESFT. Die klinische Signifikanz dieser Beobachtung muss in prospektiven Studien, die größere Patientenzahlen und alle Risikogruppen erfassen, verifiziert werden.

Key words

Ewing’s sarcoma - human leukocyte antigens - risk stratification - biomarkers - immunosurveillance - allogeneic stem cell transplantation

Schlüsselwörter

Ewing-Sarkom - humane Leukozytenantigene - Risikostratifizierung - Biomarker - Immunkontrolle - allogene Stammzelltransplantation

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