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Klin Padiatr 2013; 225(S 01): S73-S78
DOI: 10.1055/s-0033-1337967
Zum 80. Geburtstag von Prof. Riehm
© Georg Thieme Verlag KG Stuttgart · New York

ALL-REZ BFM – The Consecutive Trials for Children with Relapsed Acute Lymphoblastic Leukemia

ALL-REZ BFM – Eine Serie von klinischen Studien für Kinder mit Rezidiv einer akuten lymphoblastischen Leukämie
G. Henze
1   Pädiatrische Onkologie und Hämatologie, Charité CVK, Universitätsmedizin Berlin, Berlin
,
A. v. Stackelberg
1   Pädiatrische Onkologie und Hämatologie, Charité CVK, Universitätsmedizin Berlin, Berlin
,
C. Eckert
1   Pädiatrische Onkologie und Hämatologie, Charité CVK, Universitätsmedizin Berlin, Berlin
› Author Affiliations
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Publication History

Publication Date:
22 May 2013 (online)

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Abstract

The BFM studies for relapsed childhood acute lymphoblastic leukemia (ALL) were started in 1983, at a time when cure rates for ALL were still lower and the number of children with ALL relapse equaled about the number of children with newly diagnosed neuroblastoma. Today, relapses have become relatively rare events in ALL although, because of the frequency of ALL, they are still a significant cause of death in children and adolescents. With currently used treatment modalities, cure rates of about 50% after relapse can be achieved, and, together with the improved results of front-line therapy, the survival rate of childhood ALL is now about 90%. Most children with extramedullary and late bone marrow (BM) relapses achieve a second CR; remission rates in patients with high-risk features, however, remain still unsatisfactory. With improved techniques allogeneic hematopoietic stem cell transplant (HSCT) has become a relatively safe treatment but is not necessary for all patients as postremission therapy. HSCT is not required in children with isolated extramedullary and late BM relapses with rapid response to induction therapy measured by molecular techniques (minimal residual disease, MRD) but absolutely indicated in patients with early BM relapses and systemic relapses of T-cell ALL. For patients with insufficient response innovative therapies such as small molecules or targeted immunological or pharmacological approaches are urgently required. Efforts have to be made, therefore, in order to detect potential biological or molecular targets, which can be used for individualized, more effective and hopefully less toxic therapies in the future.

Zusammenfassung

1983 wurden die ersten BFM Studien für Patienten mit rezidivierter ALL initiiert, in einer Zeit als die Heilungsraten für ALL noch deutlich niedriger waren und die Zahl der ALL Rezidive etwa der Zahl der Kinder mit neu diagnostiziertem Neuroblastom entsprach. 30 Jahre später sind Rezi­dive seltener geworden, stellen aber aufgrund der Häufigkeit der Erkrankung immer noch einen signifikant hohen Anteil an allen Todesfällen bei Kindern und Jugendlichen dar. Mit den derzeit verfügbaren Behandlungsansätzen können etwa 50% der Rückfallpatienten erneut in anhaltende Remission gebracht werden. Zusammen mit den besseren Ergebnissen in der Erstbehandlung werden heute dauerhafte Heilungsraten von etwa 90% erreicht. Die meisten Kinder mit einem extramedullären Rückfall oder einem späten Knochenmarkrezidiv erreichen wieder eine zweite Remission; bei Hochrisikopatienten bleiben die Remissionsraten allerdings unbefriedigend. Die verbesserten Methoden der Blutstammzelltransplantation (HSCT) können die Rezidivbehandlung signifikant verbessern, aber die Transplantation ist nicht bei allen Rezidivpatienten indiziert: Die HSCT ist nicht erforderlich bei Patienten mit isoliertem extramedullären Rezidiv, oder spätem systemischen Rezidiv, falls die Leukämie rasch auf die Rezidivtherapie an­spricht. Für die Bestimmung des individuellen Ansprechens wird heute die molekulargenetische Detektion von minimaler Resterkrankung (MRD) verwendet. Die HSCT ist unbedingt bei Patienten mit frühem Knochenmarkrezidiv und bei systemischen Rückfällen von T-Zell ALL einzusetzen. Für Patienten mit schlechtem Ansprechen werden zunehmend neue Therapien mit „small molecules“, gezielten pharmakologischen oder immuntherapeutischen Interventionen erforderlich und eingesetzt. Daher müssen die Bemühungen verstärkt werden, um eine individuellere und weniger nebenwirkungsreiche Therapie zu entwickeln, die verschiedene neue Ansatzpunkte mit deutlich reduziertem Gefährdungspotential nutzen kann.

Key words

Relapsed ALL - minimal residual disease - allogeneic stem cell transplantation - targeted therapy

Schlüsselworter

Rezidiv bei ALL - minimale Resterkrankung (minimal residual disease, MRD) - Stammzelltransplantation - gezielte Therapie
 

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