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Klin Padiatr 2002; 214(4): 201-205
DOI: 10.1055/s-2002-33176
Stammzelltransplantation
© Georg Thieme Verlag Stuttgart · New York

Rezidivprophylaxe bei Kindern mit ALL-, AML- und MDS nach allogener Stammzelltransplantation durch interventionelle Immuntherapie im kritischen Stadium eines ansteigenden gemischten Chimärismus

Relapse of childhood ALL, AML and MDS after allogeneic stem cell transplantation can be prevented by donor lymphocyte infusion in a critical stage of increasing mixed chimerismJ.  F.  Beck1 , T.  Klingebiel2 , H.  Kreyenberg3 , A.  Schaudt3 , W.  Wölle3 , D.  Niethammer3 , P.  Bader3
  • 1Abteilung für Pädiatrische Hämatologie und Onkologie, Universitäts-Kinderklinik Greifswald
  • 2Abteilung für Pädiatrische Hämatologie und Onkologie, Universitäts-Kinderklinik Frankfurt
  • 3Abteilung für Pädiatrische Hämatologie und Onkologie, Universitäts-Kinderklinik Tübingen
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Publication History

Publication Date:
07 August 2002 (online)

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Zusammenfassung

Hintergrund: Rezidive sind die häufigste Todesursache für Kinder mit ALL, AML und MDS nach allogener Stammzelltranplantation (allo-SZT). Durch engmaschige Chimärismus-Verlaufsuntersuchungen konnte von uns gezeigt werden, dass Rezidive signifikant häufiger auftreten, wenn sich bei diesen Patienten ein gemischter Chimärismus mit ansteigenden autologen Anteilen (in-MC) entwickelt. Zudem kann durch interventionelle Spenderlymphozytengabe (DLI) an in-MC-Patienten Rezidiven vorgebeugt werden. Methode: In einer multizentrischen Studie soll die Wirksamkeit dieses Therapieprinzips geprüft werden. Hierzu werden bei in-MC-Patienten entweder immunsuppressiv wirkende Medikamente abgesetzt und/oder eine DLI durchgeführt. Zwischenergebnisse: Im Rahmen engmaschiger Chimärismus-Untersuchungen an 114 Kindern (ALL: n = 41, AML: n = 39, MDS: n = 34) wurden 55 einem kompletten Chimärismus (CC) und 43 einem in-MC zugeordnet. In der prospektiv untersuchten Gruppe rezidivierten die in-MC-Patienten signifikant häufiger (25/43) als die CC-Patienten (12/55, p < 0,0001). In-MC-Patienten mit Intervention wiesen eine signifikant bessere rezidivfreie Überlebensrate auf (11/24) als Patienten, bei denen nicht interveniert wurde (1/19, p < 0,01). Zwei in-MC-Patienten, bei denen interveniert wurde, entwickelten in Folge eine nicht beherrschbare, tödlich verlaufende GVHD. Schlussfolgerung: Die Daten belegen, dass die immunologische Intervention bei Kindern mit ALL, AML und MDS nach allo-SZT in einem kritischen in-MC-Stadium wirksam Rezidive verhindern kann.

Abstract

Background: Mortality in children with acute leukemias or MDS after allogeneic stem cell transplantation (allo-SCT) is mostly determined by relapses. It was recently shown by us that patients who develop increasing quantities of autologous hematopoietic cells in peripheral blood (increasing mixed chimerism, in-MC) after allo-SCT do significantly more often relapse (P < 0.0001) than patients with a complete chimerism (CC). In a small series of patients with in-MC, the relapse rate could be significantly reduced by administration of donor lymphocytes (DLI). Methodology: A prospective multicenter study was initiated under the question whether number of relapses can be significantly reduced either by withdrawal of post-transplant immunosuppression and/or by DLI in the critical stage of in-MC. Results: Highly repetitive determination of the genetic status of 114 children with acute leukemias or MDS (ALL: n = 41, AML: n = 39, MDS: n = 34) revealed 55 cases with CC and 43 with in-MC. Relapses occurred significantly (P < 0.0001) more often in patients with in-MC (25/43) than in patients with CC (12/55). In-MC-patients showed a significantly (P < 0.01) enhanced event free survival rate (11/24) when DLI was given and/or post-transplant immunosuppression was stopped compared to patients which did not receive such an interventional regimen (1/19). Two in-MC-patients developed fatal GVHD after immunological intervention. Conclusion: These data substantiate that prophylactic immunotherapy on the basis of in-MC is a powerful treatment approach to suppress relapses of acute leukemias and MDS after allo-SCT.

Schlüsselwörter

ALL - AML - MDS - Allogene Stammzelltransplantation - Chimärismus - Immuntherapie

Key words

ALL - AML - MDS - Allogeneic stem elltransplantation - Chimerism - Immunotherapy

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Prof. Dr. med. James F. Beck

Zentrum für Kinder- und Jugendmedizin, Abteilung für Pädiatrische Hämatologie und Onkologie

Soldmannstraße 15

17487 Greifswald

Email: beck@uni-greifswald.de

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