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

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.

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

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

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